Recruiting

I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer

The purpose of this study is to further advance the ability to practice personalized medicine by learning which new drug agents are most effective with which types of breast cancer tumors and by learning more about which early indicators of response (tumor analysis prior to surgery via magnetic resonance imaging (MRI) images along with tissue and blood samples) are predictors of treatment success.

ClinicalTrials.gov IDNCT01042379

PhasePHASE2

Enrollment5000

SponsorQuantumLeap Healthcare Collaborative

Age18 Years

SexALL

I'm interested View official listing

Conditions studied

Breast Neoplasms, Breast Cancer, Breast Tumors, Angiosarcoma, TNBC - Triple-Negative Breast Cancer, HER2-positive Breast Cancer, HER2-negative Breast Cancer, Hormone Receptor Positive Tumor, Hormone Receptor Negative Tumor, Early-stage Breast Cancer, Locally Advanced Breast Cancer

About this study

Interventions

Drug: Standard Therapy — Paclitaxel: 80 mg/m2 IV during the 12 weekly treatment cycles post randomization; Doxorubicin: 60 mg/m2 IV after completion of the 12 weekly treatment cycles and prior to surgery for weeks 13-16; Cyclophosphamide: 600 mg/m2 IV after completion of the 12 weekly treatment cycles and prior to surgery for weeks 13-16
Drug: AMG 386 with or without Trastuzumab — Arm is closed.
Drug: AMG 479 (Ganitumab) plus Metformin — Arm is closed.
Drug: MK-2206 with or without Trastuzumab — Arm is closed.
Drug: AMG 386 and Trastuzumab — Arm is closed.
Drug: T-DM1 and Pertuzumab — Arm is closed.
Drug: Pertuzumab and Trastuzumab — Arm is closed for Accrual. Pertuzumab: 840 mg IV (loading dose) week 1 and 420 mg every 3 weeks (weeks 4, 7, 10) post-randomization; Trastuzumab: 4 mg/kg (loading dose) week 1 and 2 mg/kg weekly (weeks 2-12) post-randomization
Drug: Ganetespib — Arm is closed.
Drug: ABT-888 — Arm is closed.
Drug: Neratinib — Arm is closed.
Drug: PLX3397 — Arm is closed.
Drug: Pembrolizumab - 4 cycle — Arm is closed.

Primary outcomes

Determine whether adding experimental agents to standard neoadjuvant medications increases the probability of pathologic complete response (pCR) over standard neoadjuvant chemotherapy for each biomarker signature established at trial entry. (Post surgery based on upto 36-week treatment)

Eligibility information

Inclusion Criteria: * Histologically confirmed invasive cancer of the breast * Clinically or radiologically measureable disease in the breast after diagnostic biopsy, defined as longest diameter greater than or equal to 25 mm (2.5cm) * No prior cytotoxic regimens are allowed for this malignancy. Patients may not have had prior chemotherapy or prior radiation therapy to the ipsilateral breast for this malignancy. Prior bis-phosphonate therapy is allowed * Age ≥18 years * ECOG performance status 0-1 * Willing to undergo core biopsy of the primary breast lesion to assess baseline biomarkers * Non-pregnant and non-lactating * No ferromagnetic prostheses. Patients who have metallic surgical implants that are not compatible with an MRI machine are not eligible. * Ability to understand and willingness to sign a written informed consent (I-SPY TRIAL Screening Consent) * Eligible tumors must meet one of the following criteria: Stage II or III, or T4, any N, M0, including clinical or pathologic inflammatory cancer or Regional Stage IV, where supraclavicular lymph nodes are the only sites metastasis * Any tumor ER/PgR status, any HER-2/neu status as measured by local hospital pathology laboratory and meets any tumor assay profile described in protocol section 4.1.2F * Normal organ and marrow function: Leukocytes ≥ 3000/μL, Absolute neutrophil count ≥ 1500/μL, Platelets ≥ 100,000/μL, Total bilirubin within normal institutional limits, unless patient has Gilbert's disease, for which bilirubin must be ≤ 2.0 x ULN, AST(SGOT)/ALT (SGPT) ≤ 1.5 x institutional ULN, creatinine \< 1.5 x institutional ULN * No uncontrolled or severe cardiac disease. Baseline ejection fraction (by nuclear imaging or echocardiography) must by ≥ 50% * No clinical or imaging evidence of distant metastases by PA and Lateral CXR, Radionuclide Bone scan, and LFTs including total bilirubin, ALT, AST, and alkaline phosphatase * Tumor assay profile must include on of the following: MammaPrint High, any ER status, any HER2 status, or MammaPrint Low, ER negative (\<5%), any HER2 status, or MammaPrint Low, ER positive, HER2/neu positive by any one of the three methods used (IHC, FISH, TargetPrint™) * Ability to understand and willingness to sign a written informed consent document (I-SPY 2 TRIAL Consent #2) Exclusion Criteria: * Use of any other investigational agents within 30 days of starting study treatment * History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agent or accompanying supportive medications. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Study locations

University of Alabama at Birmingham, Birmingham, Alabama 35294 United States
Mayo Clinic - Scottsdale, Scottsdale, Arizona 85259 United States
University of Arizona, Tucson, Arizona 85724 United States
University of California - Davis, Comprehensive Cancer Center, Davis, California 95817 United States
City of Hope, Duarte, California 91010 United States
University of California San Diego, La Jolla, California 92093-0698 United States
University of Southern California, Los Angeles, California 90033 United States
HOAG Memorial Hospital Presbyterian, Newport Beach, California 92663 United States
University of California San Francisco (UCSF), San Francisco, California 94115 United States
University of Colorado Cancer Center, Aurora, Colorado 80045 United States

Showing 10 of 42 reported sites. See the official listing for all locations.

Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.

Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-09-27.