Find Clinical Trials

Inclusion Criteria: * Female patients aged 18 to 75 years inclusive * Patients with non-metastatic breast cancer for whom adjuvant hormone therapy (anti-oestrogen or anti-aromatase) is indicated, depending on the decision of the multidisciplinary consultation meeting. * Performance status (ECOG) ≤ 2 * Patient able to read and understand French (common use) * Patient with access to an internet connection (for collection of adverse events and responses to questionnaires on the electronic platform) * Patient who has been informed and has given written consent to participate in the study * Patient affiliated to the French social security system or equivalent Exclusion Criteria: * Patient with metastatic cancer (stage IV) * Patient undergoing neoadjuvant hormone therapy * Patient who started hormone therapy prior to inclusion in the study * Patient with a history of other cancer treated by radiotherapy, chemotherapy or hormone therapy, with an end of treatment less than 2 years ago. * For patients in the experimental group: Inability of the patient to travel to the hospital to attend the initial assessment day and the proposed group outpatient workshops; follow-up of the program difficult for geographical, physical or other reasons (at the discretion of the investigator). * For patients in the control group: patients for whom telephone nursing follow-up is planned for 2 months or more or more than 4 sessions of therapeutic education. * Pregnant and breastfeeding women * Patient with a documented history of cognitive or psychiatric disorders * Refusal to participate, protected adult patient, under guardianship or curatorship

Inclusion Criteria: 1. Age ≥ 18 years at entry into the study. 2. Patient treated for hormone-dependent localized breast cancer requiring adjuvant Hormonal Therapy (HT) with tamoxifen. 3. Patients treated with tamoxifen for a maximum of 1 to 3 years. 4. Patient affiliated with a Social Security system in France. 5. Patients who signed informed consent prior to inclusion in the study and prior to any specific study procedures. Exclusion Criteria: 1. Pregnant or breastfeeding women. 2. Any psychological, family, geographical or sociological condition that does not allow the medical follow-up and/or the procedures foreseen in the study protocol to be respected. 3. Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice).

Inclusion Criteria: * ages 7.0-15.9 years * at least one clinically-relevant CBCL subscale score indicating borderline/clinical-range anxiety, depression, conduct problems, or post-traumatic stress * English fluency indicated by taking all school classes in English Exclusion Criteria: * current suicide risk, operationalized as active suicidal ideation or a history of suicide attempt or inpatient hospitalization for suicide risk within the last 3 months * presence of an eating disorder, schizophrenia spectrum disorder, autism spectrum disorder, or intellectual disability requiring special class placement in school * referral for ADHD if specifically and exclusively to address inattentiveness and/or hyperactivity-impulsivity

Inclusion Criteria: Phase 1 * Age ≥ 18 years as per self-report * Current or previous diagnosis of breast, ovarian, pancreatic, or prostate cancer as per self-report * Self-identification as Black, Latino, and/or neither Black nor Latino (i.e.,non-Latino, Non black) * Fluency in English, Haitian Creole, or Spanish as per self-report (for Spanish, we will attempt to recruit a cohort representing a variety of regions where Spanish is spoken, as informed by current data from participating sites, to achieve neutrality in the language) Fluency is defined as an answer of "well" or "very well" on the screening questions for spoken and reading ability. Phase 2: * Age ≥ 18 years as per the medical record and/or clinician referral * Current or previous diagnosis of breast, colorectal, ovarian, pancreatic, or prostate cancer meeting at least one of the applicable criteria for the cancer type as per the medical record and/or clinician referral: * Breast cancer criteria: * any diagnosis age 65 or younger; * diagnosis of triple negative breast cancer at any age; * multiple primary breast cancers at any age; * under consideration for PARP therapy; * any family history (1st, 2nd, or 3rd degree relatives) of ovarian or pancreas cancer, or 1 relative with breast cancer who meets the above criteria, or 2 relatives with breast cancer at any age; or clinician discretion) * Colorectal cancer criteria: * any diagnosis age 50 and below; * mismatch repair deficient colorectal cancer; * colorectal cancer at any age with an additional Lynch syndromerelated primary cancer at any age; * colorectal cancer at any age with a 1st or 2nd degree relative with colorectal cancer at/before age 50; * colorectal cancer at any age with 2 or more 1st or 2nd degree relatives with a Lynch syndrome-related cancer at any age * Ovarian cancer criteria: ° invasive ovarian cancer * Pancreatic cancer criteria: ° pancreatic adenocarcinoma * Prostate cancer criteria: * castrate-resistant, metastatic prostate cancer; * high-risk prostate cancer (pending pathology definition) * Fluency in English, Haitian Creole, or Spanish as per self-report. Fluency is defined as an answer of "well" or "very well" on the screening questions for spoken ability * No prior cancer genetic counseling or germline testing for cancer risk as per self-report clinician's note, and/or no clinical documentation Exclusion Criteria: Phase 1: * Individuals of impaired decision-making capacity as per a clinician's or consenting professional's judgment. * Subjects who indicate level of fluency as "not at all" or "not well". Phase 2: * Individuals of impaired decision-making capacity as per a clinician's or consenting professional's judgment. * Subjects who indicate level of fluency as "not at all" or "not well".

Inclusion Criteria: * Women with a confirmed deleterious or likely deleterious BRCA 1 germline mutation (variant class 4 or 5) * Age \>= 25 years and =\< 55 years at randomization * No evidence of breast cancer by MRI or mammography (MG) and clinical breast examination within the last 6 months prior to randomization * No clinical evidence of ovarian cancer at randomization * Negative pregnancy test at randomization for women of childbearing potential * No preventive breast surgery planned at time of randomization * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Written informed consent before any study-specific procedure is performed Exclusion Criteria: * Prior bilateral mastectomy * History of ovarian cancer (including fallopian and peritoneal cancer) * History of breast cancer * History of invasive cancer except for basal cell or squamous cell skin cancer or carcinoma in situ of the cervix, stage 1 papillary or follicular thyroid cancer, atypical hyperplasia or LCIS (lobular carcinoma in situ) * Pregnant or lactating women (within the last 2 months prior to randomization) * Unwillingness to use highly effective contraception method during and within at least 5 months after cessation of denosumab/placebo therapy in women of childbearing potential. (Note: Women of childbearing potential should be monitored for pregnancy prior to each denosumab/placebo injection) * Clinically relevant hypocalcemia (history and current condition), or serum calcium \< 2.0 mmol/L (\< 8.0 mg/dL) \* Hypocalcemia defined by calcium below the normal range (a single value below the normal range does not necessarily constitute hypocalcemia, but should be 'corrected' before dosing the subject). Monitoring of calcium level in regular intervals (usually prior to investigational product \[IP\] administration) is highly recommended * Tamoxifen, raloxifene or aromatase inhibitor use during the last 3 months prior to randomization or for a duration of more than 3 years in total (current and prior hormone replacement therapy \[HRT\] is permitted) * Prior use of denosumab * Subject has a known prior history or current evidence of osteonecrosis or osteomyelitis of the jaw, or an active dental/jaw condition which requires oral surgery including tooth extraction within 3 months of enrollment * Concurrent treatment with a bisphosphonate or an anti-angiogenic agent * Any major medical or psychiatric condition that may prevent the subject from completing the study * Known active infection with hepatitis B virus or hepatitis C virus * Known infection with human immunodeficiency virus (HIV) * Use of any other investigational product (current or prior aspirin or non-steroidal anti-inflammatory drugs \[NSAIDs\] are permitted)

Inclusion Criteria: 1. Male or Female, between the ages of 22 and 65 at the time of screening. 2. Able to read, understand, and provide written, dated informed consent prior to screening. Proficiency in English sufficient to complete questionnaires / follow instructions during fMRI assessments. Stated willingness to comply with all study procedures, including availability for the duration of the study, and to communicate with study personnel about adverse events and other clinically important information. 3. Currently diagnosed with Major Depressive Disorder (MDD) and meets criteria for a Major Depressive Episode, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5). 4. Medical records confirming a history of moderate to severe treatment-resistance as defined by a score of 7-14 on the Maudsley Staging Method (MSM 3). 5. MADRS score of ≥20 at screening (Visit 1). 6. TMS naive. 7. Access to ongoing psychiatric care before and after completion of the study. 8. Access to clinical rTMS after study completion. 9. Must be on a stable antidepressant therapeutic regimen for 6 weeks prior to study enrollment and agree to continue this regimen throughout the study period. 10. In good general health, as evidenced by medical history. 11. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation. 12. Agreement to adhere to Lifestyle Considerations throughout study duration. Lifestyle Considerations: * Abstain from becoming pregnant from the screening visit (Visit 1) until after the final study visit (Visit 13). * Continue usual intake patterns of caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate) without significant change for the duration of the study. * Abstain from alcohol for at least 24 hours before the start of each MRI and TMS session. * Participants who use tobacco products will be informed that use will be allowed only in between intervention sessions. Exclusion Criteria: 1. Pregnancy 2. Primary psychiatric condition other than MDD requiring treatment except stable comorbid anxiety disorder 3. History of or current psychotic disorder or bipolar disorder 4. Severe borderline personality disorder. 5. Diagnosis of Intellectual Disability or Autism Spectrum Disorder 6. Current moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal 7. Urine screening test positive for illicit substances 8. Active suicidal ideation (defined as an MSSI \> 8) or a suicide attempt (as defined by the C-SSRS) within the past one year 9. Any history of ECT (greater than 8 sessions) without meeting responder criteria 10. Recent (within 4 weeks of any clinical effect) or concurrent use of rapid acting antidepressant agent (i.e., ketamine or a course of ECT) 11. History of significant neurologic disease, including dementia, Parkinson's or Huntington's disease, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma 12. Untreated or insufficiently treated endocrine disorder. 13. Contraindication to receiving rTMS (e.g., metal in head, history of seizure, known brain lesion) 14. Contraindication to MRI (ferromagnetic metal in their body) 15. Treatment with an investigational drug or other intervention within the study period 16. Depth-adjusted aiTBS treatment dose \> 65% maximum stimulator output (MSO) 17. Unstable symptoms between screening and baseline as defined by a ≥ 30% change in MADRS score. 18. Any other condition deemed by the PD to interfere with the study or increase risk to the participant

Inclusion Criteria: * Breast and colorectal healthcare professionals (e.g. Clinical Nurse Specialists) working at St James' University Hospital Participating patients Phases 1 and 2: * Patients (aged 16 years or over) attending St James' University Hospital Bexley Wing, with breast and/or colorectal cancer in remission, completed their cancer treatment. * Able and willing to give informed consent * Able to read and understand English Participating patients Phase 3: * Patients (aged 16 years or over) attending St James' University Hospital Bexley Wing, with breast and/or bowel (colorectal) cancer in remission, completed their cancer treatment. * Able and willing to give informed consent * Able to read and understand English * Access to the internet Exclusion Criteria: * Patients under the age of 16 * Patients exhibiting overt psychopathology/cognitive dysfunction * Patients taking part in other clinical trials involving the completion of extensive patient reported outcome or quality of life measures

Inclusion Criteria: 1. Female, Aged \> 18; 2. HER2-positive breast cancer are defined as immunohistochemical (IHC) testing as +++, or IHC++ with FISH testing of positive; 3. Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease. 4. Patients with HER2-positive metastatic breast cancer who have progressed disease after trastuzumab treatment include the following four types of patients (Note: The following patients are in a parallel relationship): 1. Patients with HER2-positive breast cancer who have progressed during adjuvant trastuzumab treatment after surgery; or 2. Patients with HER2-positive breast cancer who have relapsed or metastasized after receiving adjuvant trastuzumab therapy; or 3. HER2-positive recurrent or metastatic BC patients who have progressed after receiving at least 4 weeks of trastuzumab as first-line treatment ; or 4. HER2-positive metastatic BC patients who have never been treated have progressed after receiving at least 4 weeks of trastuzumab as first-line treatment. 5. Genetic testing shows that the PI3K/Akt/mTOR pathway related genes are mutated; 6. ECOG PS score ≤2, estimated survival time ≥6 months, and can be followed-up; 7. Patients with measurable disease as per RECIST 1.1 criteria; 8. Cardiopulmonary function is basically normal, LVEF≥50% within 4 weeks before starting treatment; 9. An adequate liver function with the following definition: 1. Total bilirubin ≤ 1.5 times the upper limit of normal value. Patients with known Gibert's disease can be included in the group if combined bilirubin ≤ 1.5 times the upper limit of normal value; 2. AST and ALT ≤2.5 times the upper limit of the normal value; if there is liver metastasis, ≤5 times the upper limit of the normal value (the normal value is the normal value specified by this clinical trial center); 10. Have sufficient baseline hematology parameters, defined as follows: 1. ANC≥1.5 x 10\^3 /μL; 2. Platelet count ≥100 x 10\^3/μL, if it is 75-100 x 10\^3/μL, it may be included in the group, as long as the doctors believe it can be included; 3. Hemoglobin ≥9 g/dL. 11. Coagulation Indicators: International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 times the upper limit of normal, unless drugs known to change INR and aPTT are used; 12. No history of serious heart, kidney and other important organs and endocrine disease; 13. Female patients of childbearing age have a negative pregnancy test and voluntarily take effective and reliable contraceptive measures; 14. The patients voluntarily signed an informed consent form. Exclusion Criteria: Anyone who has one of the following conditions cannot be selected for this trial: 1. Participated in other clinical trials within 4 weeks; 2. Have used mTOR inhibitors in the past; 3. Previous use of Pyrotinib in first-line treatment stage; previous use of lapatinib is allowed; 4. Accompanied by immunosuppressant or chronic corticosteroid medication, or more than 25% bone marrow radiotherapy within 4 weeks; 5. Symptomatic CNS metastases or evidence of leptomeningeal disease; 6. Gastrointestinal dysfunction or gastrointestinal diseases (including active ulcers); 7. Hepatitis B or hepatitis C carriers, or other known chronic liver diseases; HIV positive; 8. Known hypersensitivity to any study medication 9. Women during pregnancy or lactation; 10. Left ventricular ejection fraction \<50%; clinical manifestations of patients with obvious arrhythmia, myocardial ischemia, severe atrioventricular block, cardiac insufficiency, and severe valvular disease; 11. Any malignancy within 5 years prior to randomization, with the exception of adequately treated in-situ carcinoma of the cervix uteri, basal or squamous cell carcinoma; 12. The researchers decide that any other medical, social or psychological conditions which are inappropriate to participate in this trial.

Inclusion Criteria: * Diagnosed patients with mild hypertension (SBP: 140\~159mmHg; DBP: 90\~99mmHg) Exclusion Criteria: * Cannot tolerate RIPC * Non-essential hypertension * patients who have uncontrolled severe arrhythmia, diabetes, electrolyte disturbance * patients who have severe organic diseases such acute myocardial infarction, cardiac insufficiency, abnormal renal function, etc.

Inclusion Criteria: * Singleton pregnant * Prior history of perinatal depression * Age between 18 and 45 years Exclusion Criteria: * Moderate to severe depression with onset during pregnancy * Severe psychiatric disorders (e.g. disorders with psychotic symptoms, schizophrenia, bipolar disorders, inpatient eating disorders and inpatient obsessive-compulsive disorders) * Previous suicide attempts without having a depressive episode * Prior history or ongoing neurological disorders (e.g. migraine or epilepsy) * Severe somatic illness * Prior history or ongoing cancer * Prior history of venous thromboembolism, myocardial infarction, cerebrovascular thromboembolism or thrombophilia, or other risk factors clinically assessed after thrombophilia screening * Deep vein thrombosis or pulmonary embolism in current pregnancy * Pregnancy-induced hypertension or preeclampsia * Pre-existing atherosclerosis or well-known cardiovascular risk factors (e.g. diabetes, hypertension) * Other contraindication for oestrogen treatment (e.g. acute liver failure, severe varicose veins) * Use of psychotropic pharmacology, except for short-term sleep support treatment * Non-fluent in Danish or pronounced vision or hearing loss * Body Mass Index (BMI) \>35 kg/m2 * Ongoing alcohol or drug abuse * Severe postpartum haemorrhage (\>1500 ml) * Severe illness in the infant or perinatal death

Inclusion Criteria: * Histologically proven unifocal adenocarcinoma * T1-T2 * Tumor size up to 2.5 cm * cN0 * Age ≥ 18 years old * Good general condition (ECOG 0-2) * Planned BCS * Written informed consent Exclusion Criteria: * Tumor close to skin or chest wall * Pure non-invasive tumor * Prior RT to the chest * Neoadjuvant chemotherapy * Collagenopathies * Coagulation or autoimmunitary disorders * Previous malignancies

Inclusion Criteria: * minimum age of 18 years * traumatic, tumor, ischemic, or hemorrhagic pathology of the posterior fossa * GCS of 8 or less. Exclusion Criteria: * coagulation disorders * multi-organ failure * multiple pathologies * open head trauma to the posterior fossa with leakage of nervous tissue

Inclusion Criteria: * Women or men with histologically confirmed invasive mammary carcinoma. * Known triple negative ER/PR/HER2 receptor status as defined by: * ER and PR less than or equal to 10% and * HER2 negative based on one of the following: * IHC 0 or 1+ * IHC 2+ and FISH negative * IHC 2+ and FISH equivocal and no indication for HER2 targeted therapy based on the treating investigators discretion (i.e., HER2: CEP17 ratio \< 2.0 or HER2 total copy number \<6) * Patients who plan to undergo neoadjuvant chemotherapy prior to definitive surgical management. Participants are eligible up to 2 weeks after initiating neoadjuvant chemotherapy. * ECOG performance status of 0, 1 or 2. * Age ≥ 18. * The effects of high dose vitamin D on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative). Exclusion Criteria: * Patients with nephrolithiasis within the past year. * Patients with known sarcoidosis. * Patients with corrected calcium \>10.5 mg/dL within 30 days prior to initiation of chemotherapy. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to vitamin D. * Pregnant women are excluded from this study because vitamin D supplementation greater than the recommended daily allowance (RDA) is a pregnancy class C agent with no adequate or well controlled studies in humans. * Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with high dose vitamin D (greater than RDA), women who are breastfeeding are excluded from this study. * Prior treatment for this malignancy including surgery, radiation therapy, chemotherapy, hormonal therapy or investigational agent prior to study entry. * Patients currently taking Vitamin D at a dose of 50,000 International Units (IU) once weekly.

Inclusion Criteria: Parts 1, 2, 3 and 4 Patients must meet all the following criteria to be eligible to participate in the study: 1. Are ≥18 years old males or females. 2. Are capable of understanding and have voluntarily signed the informed consent document and willing to comply with study requirements. 3. Have histologically or cytologically confirmed diagnosis of metastatic or advanced-stage solid tumor that is refractory to standard therapy (For Part 1 only; see modified inclusion criteria #13, 15 and 18 for Parts 2, 3, and 4, respectively). 4. Have measurable disease according to the RECIST 1.1. 5. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 6. Have an expected survival of at least 3 months. 7. Have a negative pregnancy test result confirmed by a serum beta-human chorionic gonadotropin (β-HCG) test (for women of childbearing potential \[WOCBP\]) performed at Screening and have a negative pregnancy urine test result on Cycle 1, Day 1. This is not applicable to patients who are unable to become pregnant, including those with bilateral oophorectomy, salpingectomy, tubal ligation and/or hysterectomy or postmenopausal or those that have had definitive radiation therapy to the pelvis. WOCBP are considered postmenopausal if 12 months of spontaneous amenorrhea, or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone levels \> 40 mIU/mL, or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy. 8. WOCBP who are sexually active with a non-sterilized male partner (sterilized males should be ≥6 months post vasectomy and have obtained documentation of the absence of sperm in the ejaculate) should agree to remain abstinent (refrain from sexual intercourse of any kind) or use 2 effective methods of contraception, including at least 1 method with a failure rate of \<1% per year, during the treatment period and for at least 6 months for both female and male patients, following the last dose of TH1902. Periodic abstinence (e.g., calendar, symptothermal, and post-ovulation), withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together. • Effective contraceptive measures include the following: * Intrauterine device (e.g., IUD) or intrauterine system plus one barrier method. * Oral, intravaginal, or transdermal combined (estrogen and progestogen) hormonal contraceptive associated with the inhibition of ovulation plus one barrier method. * Oral, implantable, or injectable progestogen-only hormonal contraceptive associated with the inhibition of ovulation plus one barrier method. * Bilateral tubal occlusion at least 6 weeks before study drug administration. * Sterilization of male partner (at least 6 months prior to screening). For WOCBP in on the study, the vasectomized male partner should be the sole partner for that patient and must have obtained documentation of the absence of sperm in the ejaculate. * True sexual abstinence when this is in line with the preferred and usual lifestyle of the study patient. * Effective barrier methods are male or female condoms, diaphragms, and spermicides. 9. WOCBP must agree to ongoing pregnancy testing during the course of the study and must agree not to donate ova during and after treatment with TH1902. Male patients must refrain from donating sperm during the study and for at least 6 months following the last dose of TH1902. 10. Male patients with WOCBP partners must agree to remain abstinent (refrain from sexual intercourse of any kind) or use a condom (latex condom is recommended) during the treatment period and for at least 6 months after the last dose of TH1902 to avoid exposing the embryo, if the vasectomy has been performed less than 6 months or documentation of the absence of sperm in the ejaculate has not been obtained. Periodic abstinence (e.g., calendar, symptothermal, and post-ovulation,), withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together. 11. Patients with known Human Immunodeficiency Virus (HIV)/Hepatitis B (HBV)/Hepatitis C (HCV) will be allowed to enter the study provided the following criteria are met: * Patients with HIV infection must have CD4+ T-cell (CD4+) counts ≥ 350 cells/µL. * The following eligibility criteria are for patients with evidence of chronic HBV infection or patients with history of chronic HCV or who are virologically suppressed on HCV treatment: * Liver-related laboratory eligibility criteria should be the same as that for the general population. * Exceptions: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and bilirubin criteria may be less stringent in patients with cancers such as hepatocellular carcinoma and cholangiocarcinoma in whom hepatic function based on Child-Pugh score should be used. * Patients with chronic HBV infection with active disease who meet the criteria for anti-HBV therapy should be on a suppressive antiviral therapy prior to initiation of cancer therapy. * Patients on concurrent HCV treatments must have HCV below the limit of quantification. * Patients with untreated and stable HCV can be enrolled provided that the patient is not at risk for hepatic decompensation. 12. Recovered from any previous therapy related toxicity to ≤Grade 1 at study entry (except for stable sensory neuropathy ≤Grade 2 and alopecia) (for Parts 1 and 2 only; see modified inclusion criteria #14 for Part 3 and 17 for Part 4). Part 2 Patients must meet the following modified criterion to enter Part 2 of the study: 13. Histologically or cytologically confirmed TNBC, HR+ breast cancer, epithelial ovarian cancer, endometrial cancer, cutaneous melanoma, thyroid cancer, SCLC, prostate cancer or other cancer known to express SORT1 that is refractory or resistant to standard therapy (replaces inclusion criterion #3). Part 3 Patients must meet the following additional and/or modified inclusion criteria to enter Part 3 of the study: 14. Recovered from any previous therapy related toxicity to ≤Grade 1 at study entry (except for ≤Grade 2 alopecia) (replaces inclusion criterion #12). 15. Diagnosed with histologically or cytologically confirmed high grade serous ovarian cancer, including high grade peritoneal or fallopian tube, or high grade endometrioid cancer, that is refractory or resistant to standard therapies, not considered platinum sensitive, and where current therapy is not considered to be providing benefit. Patients with clear-cell, mucinous, low grade serous ovarian cancer or carcinosarcoma are not eligible for the study (replaces inclusion criterion #3). 16. Patient received a maximum of 8 prior cancer treatment regimens, including adjuvant/neoadjuvant. Part 4 Patients must meet the following additional and/or modified inclusion criteria to enter Part 4 of the study: 17. Recovered from any previous therapy related toxicity to ≤Grade 1 at study entry (except for ≤Grade 2 alopecia) (replaces inclusion criteria #12 and #14). 18. Diagnosed with histologically or cytologically confirmed cancers, where TH1902 has been studied and/or showed activity, that is refractory or resistant to standard therapies, and where current therapy is not considered to be providing benefit (replaces inclusion criteria #3 and #15). 19. Patient received a maximum of 8 prior cancer treatment regimens, including adjuvant/neoadjuvant Exclusion Criteria: Parts 1, 2, 3 and 4 Patients who meet any one of the following criteria at baseline will be excluded from study participation: 1. Have received chemotherapy, biologic therapy, immunotherapy, radiotherapy (except palliative radiation delivered to \<20% of bone marrow), or investigational agents within 4 weeks before the first dose of study drug. Patients who have received targeted therapy (invest

Inclusion Criteria: * Participants must be ≥ 18 years old. * Participants with a clinical T1 or T2 invasive ductal or lobular breast carcinoma, regardless of estrogen/progesterone/human epidermal growth factor receptor 2 (HER2) receptor status. * Participants with clinical (on palpation) N0 and up to two suspicious lymph nodes on axillary ultrasound. * Participant with biopsy-proven positive axillary disease made by core needle biopsy or fine-needle aspiration. * Participants must have an Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status less than 2. * Participants must understand, accept, and have signed the approved consent form. Exclusion Criteria: * Participant with previous ipsilateral axillary surgery, including sentinel lymph node biopsy. * Participants with distant metastases. * Participants that have had previous radiotherapy to the axillary nodes. * Participants who received neoadjuvant therapy. * If the injection of blue dye is planned, patients with hypersensitivity or allergy to isosulfan blue, patent blue, methylene blue or radiocolloid dye. * Participants who are unable to provide informed consent.

Inclusion Criteria: * Ability to confirm voluntary participation and agree to all trial purposes by signing and dating the informed consent forms; * Participants with 18 years of age or greater; * Participants presenting the diagnosis of type II diabetes mellitus, and who did not reach the therapeutic goals of HbA1c with previous dietary, physical exercise guidance and at least 3 months with two anti-hyperglycemic agents (dual therapy); * HbA1c ≥ 7,5% and ≤ 10,5% and fasting blood glucose \> 100 mg/dL at the screening visit; * BMI (body mass index) \> 19 Kg/m2 and ≤ 45 Kg/m2. Exclusion Criteria: * Any clinical and laboratory findings that, in the judgment of the investigator, may interfere with the safety of research participants; * History of alcohol abuse or illicit drug use; * Participation in a clinical trial in the year prior to this study; * Pregnancy or risk of pregnancy and lactating patients; * Known hypersensitivity to the formula components used during the clinical trial; * Type 1 diabetes mellitus; * Fasting blood glucose \> 300 mg/dL; * Risk factors for volume depletion; * Impaired renal function and end-stage renal disease; * Participants with current treatment and continued for more than 15 days with systemic steroids at the time of informed consent; * Impaired hepatic function; * Medical history of pancreatic diseases that may suggest insulin deficiency; * Bariatric surgery in the last two years and/ or other gastrointestinal surgeries that can cause chronic malabsorption syndrome; * Condition that, in the investigator's judgment, may favor clinically significant changes in CPK levels; * Medical history of acute coronary syndrome, stroke, unstable congestive heart failure, or respiratory failure within 6 months prior to informed consent; * Current medical history of cancer and/ or cancer treatment in the last 5 years; * Medical history of metabolic acidosis and/or using drugs that may cause lactic acidosis; * Medical history of blood dyscrasia or any other hemolytic disorders; * Participants using sulfonylureas and/or insulin therapy; * Treatment with anti-obesity drugs for less than 2 months or with dose change in the last 2 months.

Inclusion Criteria: * Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of triple negative breast cancer or ER+/Her2 will be enrolled in this study. * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 30 days prior to the date of allocation/randomization * Histologically or cytologically-confirmed TNBC (defined as ER \<5%, PR \<5%, HER- 2-neu 0-1+ by IHC or FISH-negative or per MD discretion). * Histologically of cytologically-confirmed ER+ breast cancer, defined as ER 1-100% and HER-2/neu 0-1+ by IHC or FISH-negative * Metastatic or recurrent TNBC. * Metastatic or recurrent ER+ breast cancer * For mTNBC patients, prior receipt of ICI with progression and/or PDL1-negative. PDL-1 status is not used to determine eligibility among mER+BC patients * Note: PDL1-status may be determined on tissues from either primary or mTNBC. Determination of PD-L1 status by any prototype assays is acceptable. PD-L1 status is required or archival tissue must be readily available for testing during screening if status was not previously determined. * The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. * Have measurable disease based on RECIST 1.1. There should be at least one radiographically-confirmed non-bone metastatic lesion that will not undergo RT and is measurable based on RECIST and suitable for repeated measurements. * Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. * No more than 3 prior lines of systemic therapy (including conventional cytotoxics, targeted therapies, biologics, or other invesigational systemic treatments) for inoperable/recurrent or metastatic disease in the TNBC cohort. A line of treatment in this instance refers to any systemic therapy directed at metastatic TNBC and which was discontinued due to disease progression. Treatment discontinued due to toxicity will not be counted. Systemic therapy previously delivered for hormone-receptor positive or Her2+ breast cancer (that has now switched to TNBC subtype) will not count as a prior line of treatment. Any number of prior lines of treatment for mER+BC are allowed. * At least one tumor site for which palliative RT is considered clinically appropriate. The site under consideration can be a metastatic site, or uncontrolled primary/locally recurrent disease in the breast/chest wall or in the nodes. Prior radiotherapy to the target site is allowed. Investigators should remain within departmental radiotherapy for normal tissue; exceptions should be discussed with the PI. * Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion. Formalin- fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Newly-obtained is defined as a specimen obtained up to 30 days prior to initiation of treatment on Day 1 of pembro. (Note: PI can waive this requirement at his discretion if specimen collection is deemed unfeasible). * A female participant is eligible to participate if she is not pregnant (see Appendix C), not breastfeeding, and at least one of the following conditions applies: 1. Not a woman of childbearing potential (WOCBP) as defined in Appendix C OR 2. A WOCBP who agrees to follow the contraceptive guidance in Appendix C during the treatment period and for at least one month after the last dose of study treatment. * Have adequate organ function as defined in the following table (Table 2). Specimens must be collected within 30 days prior to the start of study treatment. Table 2 Adequate Organ Function Laboratory Values System: Laboratory Value Hematological Absolute neutrophil count (ANC): ≥ 1500/µL Platelets: ≥ 100 000/µL Hemoglobin: ≥ 9.0 g/dL with no blood transfusion in the past 28 days Renal Creatinine: 1.5 x ULN OR Measured or calculatedb creatinine clearance (GFR can also be used in place of creatinine or CrCl): ≥ 51 mL/min Hepatic Total bilirubin: ≤ 1.5 x ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels \>1.5 x ULN AST (SGOT) and ALT (SGPT): ≤ 2.5 x ULN (≤ 5 x ULN for participants with liver metastases) Coagulation International normalized ratio (INR) OR prothrombin time (PT); Activated partial thromboplastin time (aPTT): ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal. a - Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks. b - Creatinine clearance (CrCl) should be calculated per institutional standard. Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies. * Participant must agree not to breastfeed during the study or for 180 days after the last dose of study treatment. * Participant receiving corticosteroids may continue as long as their dose is stable for at least 4 weeks prior to initiating protocol therapy. * Ability to swallow (whole) and retain oral medications. Exclusion Criteria: * Receipt of \> 3 lines of systemic therapy in mTNBC patients * A WOCBP who has a positive urine pregnancy test within 72 hours or a serum pregnancy test within 14 days prior to treatment (see Appendix C). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * A minimum 2-week washout required for all anti-cancer agents, including cytotoxic chemotherapeutic agents, immunotherapy, biologic therapy, and targeted therapies. A 3-4 week washout is preferred when reasonable. * Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication. * Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (preferred) or a minimum of 2 weeks prior to the start of study treatment. * Note: Participants must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy may be eligible. * Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment. * Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease. * Has previously experienced grade 3 or higher immune-mediated adverse events from prior courses of immunotherapy. * Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. ° Note: Seasonal influenza vaccines for injection are generally inactivated flu vac

Inclusion Criteria: * Histologically and/or cytologically confirmed ER positive, HER-2 negative breast cancer * Female patients must be post-menopausal; female patients who are pre-menopausal must have ovarian suppression using LHRH agonist while on study * Clinical and/or radiographic progression during treatment with or within 28 days after discontinuation of first line of treatment with a CDK 4/6 inhibitor and an aromatase inhibitor (AI) for advanced/metastatic disease * Evidence of clinically and/or radiologically documented disease * ≥ 18 years of age * ECOG performance status of 0 or 1 * No concurrent anti-cancer therapy and must satisfy the following criteria for previous therapy * Must not have received more than one prior line of treatment with a CDK 4/6 inhibitor and an AI in the advanced disease setting. * Treatment with CDK 4/6 inhibitor and AI must have been the most recent treatment prior to registration for this study * Adequate hematology and organ function, in the absence of growth factors * Absolute neutrophils \> 1.5 x 10\^9/L * Platelets ≥ 100 x 10\^9/L * Hemoglobin \> 90 g/L * Total Bilirubin ≤ 1.5 x ULN (upper limit of normal) or ≤ 3 x ULN if confirmed Gilbert's Syndrome * ALT and AST ≤ 2.5 x ULN (or ≤ 5.0 x ULN if liver or bone metastasis) * Alkaline phosphatase ≤ 2.0 x ULN (or ≤ 5.0 x ULN if liver metastases, ≤ 7.0 x ULN if bone metastasis) * Fasting glucose ≤ 8.3 mmol/L * HbA1c ≤ 7.5% * Serum albumin ≥ 30 g/L * INR ≤ 1.2 * Serum Creatinine or Creatinine clearance ≤ 1.5 x ULN or ≥ 50 mL/min; measured directly by 24-hour urine sampling or as calculated by Crockcroft and Gault equation Exclusion Criteria: * Untreated or symptomatic CNS metastases, radiation treatment for CNS metastases within 28 days * Active inflammatory bowel disease, bowel inflammation, inability to swallow oral medication or GI condition that alters oral absorption * Prior treatment with fulvestrant, selective estrogen receptor degraders (SERDs) or known inhibitors of the PI3K pathway including PI3K inhibitors, AKT inhibitors, or mTOR inhibitors * Mean QT interval corrected for heart rate (QTc) ≥ 480 msec by ECG or history of familial long QT syndrome * Active or uncontrolled infections or serious illnesses or medical conditions * Clinically significant liver diseases * History of lung disease or history of opportunistic infections * Type 1 or Type 2 diabetes mellitus requiring insulin * Grade ≥ 2 uncontrolled hypercholesterolemia or hypertriglyceridemia * Known abnormalities in coagulation * History of hypersensitivity to the study drugs or components * Pregnant or lactating women

Inclusion Criteria: * Female or male patients with invasive breast cancer who have had mastectomy and have a chest wall reconstruction in progress or completed. * Age ≥ 30 years * Final AJCC Stage IIa - IIIa (pathologic stage T0N1a-2a, T1N1a-2a, T2N1a-2a, T3N0-2a, all M0 status). Pathological stage for all patients not receiving neoadjuvant chemotherapy. Higher of the clinical or pathological T and N stage, if receiving neoadjuvant chemotherapy. T3N0 patients, either clinically by imaging before neoadjuvant chemotherapy, or by pathological stage at the time of surgery, are eligible. Exceptions to these criteria (e.g. for T4 or N3 patients) are possible after discussion with PI. * Histologically negative tumor margin. * ECOG Performance Status of 0 or 1 Exclusion Criteria: * Patients with distant metastasis. * Patients who are pregnant or breastfeeding. * Prior radiation therapy to the ipsilateral or contralateral breast or thorax. * All patients with clinical, radiographic or pathological T4, N3 or involved internal mammary disease (N1b, N1c, and N2b) will not be eligible to enroll. * Medical condition such as uncontrolled infection (including HIV), uncontrolled diabetes mellitus, or connective tissue diseases (lupus, systemic sclerosis, or other collagen vascular diseases) that, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient. * Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have "currently active" malignancies if they have completed therapy and are considered by their physicians to be at \<5% risk of relapse within 3 years. * Concomitant anti-neoplastic treatment is not allowed during protocol treatment and should be completed at least 2 weeks prior to commencement of protocol treatment, with resolution of associated acute toxicities. However endocrine therapies (tamoxifen or aromatase inhibitors), anti-HER2 therapy and bisphosphonates are permitted without restriction even during protocol treatment. Standard-of-care maintenance treatments such as pembrolizumab and capecitabine are permitted during protocol treatment. All of these treatments are delivered routinely as SOC during conventional radiotherapy. * Unwilling or unable to participate in all required study evaluations and procedures. Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local patient privacy regulations).

Inclusion Criteria: * Signed Informed Consent * Normal Tension Glaucoma with typical nerve fiber layer defects in red-free photographs and/or optical coherence tomography (OCT) and possible equivalent visual field defects, IOP never more than 21 mmHg, and open anterior chamber angle * Glaucoma stable with current medication assessed by a glaucoma specialist * Clinically significant cataract Exclusion Criteria: * Secondary Glaucoma e.g. due to previous injury or uveitis * Exfoliation syndrome * Pigment dispersion syndrome * Previous transscleral or endoscopic cyclophotocoagulation * Previous other glaucoma surgery * Cataract due to eye injury or congenital cataract * Zonular weakness due to Marfan syndrome or other * Previous retinal detachment * Previous intraocular surgery like vitrectomy and other retinal surgery * Wet age-related macular degeneration * Diabetic retonopathy * Previous corneal transplant or previous refractive surgery * Fuchs' dystrophy and other abnormalities compromising corneal clarity like scars * The patient does not want to participate in the study * The glaucoma progresses on current IOP * The patient does not speak Finnish, Swedish or English * Dementia * Only eye with vision worse than 20/200 or loss of central visual field