I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer (I-SPY)
Breast Neoplasms, Breast Cancer, Breast Tumors
About this trial
This is an interventional treatment trial for Breast Neoplasms focused on measuring Neoadjuvant, Breast, Cancer, Neoplasm, Adaptive, pCR, Pathologic Complete Response, Biomarkers signature, MRI Volume, Endocrine Therapy, Chemotherapy, Immunotherapy
Eligibility Criteria
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
Sites / Locations
- University of Alabama at BirminghamRecruiting
- Mayo Clinic - Scottsdale
- University of Arizona
- City of HopeRecruiting
- University of California San DiegoRecruiting
- University of Southern CaliforniaRecruiting
- HOAG Memorial Hospital PresbyterianRecruiting
- University of California San Francisco (UCSF)Recruiting
- University of ColoradoRecruiting
- Yale Cancer CenterRecruiting
- Georgetown University Medical CenterRecruiting
- Moffitt Cancer CenterRecruiting
- Winship Cancer Institute of Emory UniversityRecruiting
- University of ChicagoRecruiting
- Loyola UniversityRecruiting
- University of Kansas
- Herbert-Herman Cancer Center, Sparrow HospitalRecruiting
- University of MinnesotaRecruiting
- Mayo ClinicRecruiting
- Rutgers Cancer Institute of New JerseyRecruiting
- Montefiore Medical Center
- Columbia University Medical CenterRecruiting
- University of Rochester Wilmot Cancer InstituteRecruiting
- Wake Forest Baptist Comprehensive Cancer CenterRecruiting
- Cleveland ClinicRecruiting
- Oregon Health & Science Institute (OHSU)Recruiting
- University of Pennsylvania (U Penn)Recruiting
- University Pittsburgh Medical Center
- Sanford Clinical ResearchRecruiting
- Vanderbilt University Medical CenterRecruiting
- University of Texas, Southwestern Medical Center
- University of Texas, M.D. Anderson Cancer Center
- Inova Health System
- Swedish Cancer Institute
- University of Washington
Arms of the Study
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Active Comparator
Experimental
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Standard Therapy
AMG 386 with or without Trastuzumab
AMG 479 plus Metformin
MK-2206 with or without Trastuzumab
T-DM1 and Pertuzumab
Pertuzumab and Trastuzumab
Ganetespib
ABT-888
Neratinib
PLX3397
Pembrolizumab 4 cycle
Talazoparib plus Irinotecan
Patritumab with or without Trastuzumab
Pembrolizumab 8 cycle
SGN-LIV1A
Durvalumab plus Olaparib
SD-101 + Pembrolizumab
Tucatinib
Cemiplimab
Cemiplimab plus REGN3767
Trilaciclib with or without trastuzumab + pertuzumab
SYD985 ([vic-]trastuzumab duocarmazine)
Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab
Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab
Endocrine Optimization Pilot: Amcenestrant Monotherapy
Endocrine Optimization Pilot: Amcenestrant + Abemaciclib
Endocrine Optimization Pilot: Amcenestrant + Letrozole
ARX788 in Block A and followed by SOC in Block B
ARX788 + Cemiplimab in Block A and followed by SOC in Block B
VSV-IFNβ-NIS (VOYAGER V1™; VV1) + Cemiplimab in Block A and followed by SOC in block B
Datopotamab Deruxtecan in Block A and followed by SOC in block B
Datopotamab Deruxtecan + Durvalumab in Block A and followed by SOC in block B
Zanidatamab in Block A and followed by SOC in block B
Endocrine Optimization Pilot: Lasofoxifene
Endocrine Optimization Pilot: (Z)-Endoxifen
Endocrine Optimization Pilot: ARV-471
Endocrine Optimization Pilot: ARV-471 + Letrozole
Paclitaxel, Herceptin followed by Doxorubicin and Cyclophosphamide treatment depending on HR/HER-2 status.
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