I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer
- Conditions
- HER2-negative Breast CancerHormone Receptor Positive TumorAngiosarcomaTNBC - Triple-Negative Breast CancerBreast NeoplasmsBreast TumorsHER2-positive Breast CancerHormone Receptor Negative TumorBreast CancerEarly-stage Breast Cancer
- Interventions
- Drug: Standard TherapyDrug: AMG 386 with or without TrastuzumabDrug: AMG 479 (Ganitumab) plus MetforminDrug: SYD985 ([vic-]trastuzumab duocarmazine)Drug: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumabDrug: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumabDrug: Datopotamab deruxtecan + DurvalumabDrug: Rilvegostomig + TDXdDrug: AMG 386 and Trastuzumab
- Registration Number
- NCT01042379
- Lead Sponsor
- QuantumLeap Healthcare Collaborative
- Brief Summary
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.
- Detailed Description
I-SPY2 will assess the efficacy of novel drugs in sequence with standard chemotherapy. The goal is identify treatment strategies for subsets on the basis of molecular characteristics (biomarker signatures) of their disease with high estimated pCR rate. As described for previous adaptive trials, novel regimens with sufficiently high activities alone and contribute to treatment strategies that show a high Bayesian predictive probability of being more effective than the dynamic control will graduate from the trial with their corresponding biomarker signature(s). Treatment strategies will be dropped if they show a low probability of improved efficacy with any biomarker signature. New drugs will enter as those that have undergone testing complete their evaluation.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 5000
- 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)
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cemiplimab Cemiplimab Novel Investigational Agent. Arm is closed. Cemiplimab plus REGN3767 Cemiplimab plus REGN3767 Novel Investigational Agent. Arm is closed. Sarilumab + Cemiplimab + Paclitaxel in Block B followed by SOC Block C Sarilumab + Cemiplimab + Paclitaxel Novel investigational Agent Tucatinib Tucatinib plus trastuzumab and pertuzumab Arm is closed. Endocrine Optimization Pilot: ARV-471 + Letrozole ARV-471 + Letrozole Novel investigational Agent Endocrine Optimization Pilot: ARV-471 + Abemaciclib ARV-471 + Abemaciclib Novel investigational Agent Endocrine Optimization Pilot: (Z)-Endoxifen + Abemaciclib Endoxifen + Abemaciclib Novel investigational Agent Standard Therapy Standard Therapy Paclitaxel, Herceptin followed by Doxorubicin and Cyclophosphamide treatment depending on HR/HER-2 status. AMG 386 with or without Trastuzumab AMG 386 with or without Trastuzumab Arm is closed. AMG 386 with or without Trastuzumab AMG 386 and Trastuzumab Arm is closed. AMG 479 plus Metformin AMG 479 (Ganitumab) plus Metformin Arm is closed. MK-2206 with or without Trastuzumab MK-2206 with or without Trastuzumab Arm is closed. T-DM1 and Pertuzumab T-DM1 and Pertuzumab Arm is closed. Pertuzumab and Trastuzumab Pertuzumab and Trastuzumab Novel Control Investigational Agent. Arm is closed. Ganetespib Ganetespib Arm is closed. ABT-888 ABT-888 Arm is closed. Neratinib Neratinib Arm is closed. PLX3397 PLX3397 Arm is closed. Pembrolizumab 4 cycle Pembrolizumab - 4 cycle Arm is closed. Talazoparib plus Irinotecan Talazoparib plus Irinotecan Arm is closed. Patritumab with or without Trastuzumab Patritumab and Trastuzumab Arm is closed. Pembrolizumab 8 cycle Pembrolizumab - 8 cycle Arm is closed. Durvalumab plus Olaparib Durvalumab plus Olaparib Arm is closed. SD-101 + Pembrolizumab SD-101 + Pembrolizumab Arm is closed. Trilaciclib with or without trastuzumab + pertuzumab Trilaciclib with or without trastuzumab + pertuzumab Novel Investigational Agent. Arm is closed. SYD985 ([vic-]trastuzumab duocarmazine) SYD985 ([vic-]trastuzumab duocarmazine) Novel Investigational Agent. Arm is closed. Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab Novel Investigational Agent. Arm is closed. DAN222 + Niraparib in Block A and followed by SOC in Block B Dan222 + Niraparib Novel investigational Agent Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab Novel Investigational Agent. Arm is closed. Endocrine Optimization Pilot: Amcenestrant Monotherapy Amcenestrant Novel Investigational Agent. Arm is closed. Endocrine Optimization Pilot: Amcenestrant + Abemaciclib Amcenestrant + Abemaciclib Novel Investigational Agent. Arm is closed. Endocrine Optimization Pilot: Amcenestrant + Letrozole Amcenestrant + Letrozole Novel Investigational Agent. Arm is closed. ARX788 in Block A and followed by SOC in Block B ARX788 Novel investigational Agent followed by SOC ARX788 + Cemiplimab in Block A and followed by SOC in Block B ARX788 + Cemiplimab Novel investigational Agent followed by SOC. Arm is closed. VSV-IFNβ-NIS (VOYAGER V1™; VV1) + Cemiplimab in Block A and followed by SOC in block B VV1 + Cemiplimab Novel investigational Agent followed by SOC Datopotamab Deruxtecan in Block A and followed by SOC in block B Datopotamab deruxtecan Novel investigational Agent followed by SOC Datopotamab Deruxtecan + Durvalumab in Block A and followed by SOC in block B Datopotamab deruxtecan + Durvalumab Novel investigational Agent followed by SOC Endocrine Optimization Pilot: Lasofoxifene Lasofoxifene Novel investigational Agent Endocrine Optimization Pilot: (Z)-Endoxifen Z-endoxifen Novel investigational Agent Endocrine Optimization Pilot: ARV-471 ARV-471 Novel investigational Agent Rilvegostomig + TDXd in Block A and followed by SOC in Block B Rilvegostomig + TDXd Novel investigational Agent SGN-LIV1A SGN-LIV1A Arm is closed. Zanidatamab in Block A and followed by SOC in block B Zanidatamab Novel investigational Agent followed by SOC
- Primary Outcome Measures
Name Time Method 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
- Secondary Outcome Measures
Name Time Method Establishing predictive and prognostic indices based on qualification and exploratory markers to predict pCR and residual cancer burden (RCB). Blood and Tissue Collection: Baseline, Post-Randomization, Pre-AC, Pre- and Post-Surgery To determine three- and five-year relapse-free survival (RFS) and OS among the treatment arms. Three- and Five-Year Post-surgery Follow-up MRI Volume Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery To determine incidence of adverse events (AEs), serious adverse events (SAEs), and laboratory abnormalities of each investigational agent tested. Post-Randomization, Pre-AC, Pre-Surgery, Post-Surgery upto One Year during follow-up
Trial Locations
- Locations (36)
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
University of Texas, Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Kansas
🇺🇸Westwood, Kansas, United States
Herbert-Herman Cancer Center, Sparrow Hospital
🇺🇸Lansing, Michigan, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Sanford Clinical Research
🇺🇸Sioux Falls, South Dakota, United States
University of Texas, M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
University of Washington
🇺🇸Seattle, Washington, United States
University of California San Francisco (UCSF)
🇺🇸San Francisco, California, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Oregon Health & Science Institute (OHSU)
🇺🇸Portland, Oregon, United States
University of Rochester Wilmot Cancer Institute
🇺🇸Rochester, New York, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
University of Southern California
🇺🇸Los Angeles, California, United States
City of Hope
🇺🇸Duarte, California, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
Mayo Clinic - Scottsdale
🇺🇸Scottsdale, Arizona, United States
University of California San Diego
🇺🇸La Jolla, California, United States
HOAG Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Loyola University
🇺🇸Maywood, Illinois, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Wake Forest Baptist Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Laura and Isaac Perlmutter Cancer Center / NYU Langone Health
🇺🇸New York, New York, United States
University of Pennsylvania (U Penn)
🇺🇸Philadelphia, Pennsylvania, United States
Inova Health System
🇺🇸Falls Church, Virginia, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States