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

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ClinicalTrials.gov Identifier: NCT01042379
Recruitment Status : Recruiting
First Posted : January 5, 2010
Last Update Posted : April 27, 2021
Sponsor:
Information provided by (Responsible Party):
QuantumLeap Healthcare Collaborative

Tracking Information
First Submitted Date  ICMJE December 31, 2009
First Posted Date  ICMJE January 5, 2010
Last Update Posted Date April 27, 2021
Actual Study Start Date  ICMJE March 1, 2010
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 4, 2010)
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. [ Time Frame: Post surgery based on upto 24-week treatment ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2016)
  • Establishing predictive and prognostic indices based on qualification and exploratory markers to predict pCR and residual cancer burden (RCB). [ Time Frame: 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. [ Time Frame: Three- and Five-Year Post-surgery Follow-up ]
  • To determine incidence of adverse events (AEs), serious adverse events (SAEs), and laboratory abnormalities of each investigational agent tested. [ Time Frame: Post-Randomization, Pre-AC, Pre-Surgery, Post-Surgery upto One Year during follow-up ]
  • MRI Volume [ Time Frame: Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2010)
  • Establishing predictive and prognostic indices based on qualification and exploratory markers to predict pCR and residual cancer burden (RCB). [ Time Frame: 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. [ Time Frame: Three- and Five-Year Post-surgery Follow-up ]
  • To determine incidence of adverse events (AEs), serious adverse events (SAEs), and laboratory abnormalities of each investigational agent tested. [ Time Frame: Post-Randomization, Pre-AC, Pre-Surgery, Post-Surgery upto One Year during follow-up ]
  • MRV [ Time Frame: Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer
Official Title  ICMJE I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)
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-SPY will compare the efficacy of novel drugs in combination with standard chemotherapy with the efficacy of standard therapy alone. The goal is identify improved treatment regimens for subsets on the basis of molecular characteristics (biomarker signatures) of their disease. As described for previous adaptive trials, regimens that show a high Bayesian predictive probability of being more effective than standard therapy will graduate from the trial with their corresponding biomarker signature(s). Regimens 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Neoplasms
  • Breast Cancer
  • Breast Tumors
  • Angiosarcoma
Intervention  ICMJE
  • 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
    Other Name: Paclitaxel (Taxol); Doxorubicin (Adriamycin)
  • Drug: AMG 386 with or without Trastuzumab
    Arm is closed.
    Other Name: AMG 386 (Trebananib); (Trastuzumab) Herceptin
  • Drug: AMG 479 (Ganitumab) plus Metformin
    Arm is closed.
    Other Name: Ganitumab
  • Drug: MK-2206 with or without Trastuzumab
    Arm is closed.
    Other Name: (Trastuzumab) Herceptin
  • Drug: AMG 386 and Trastuzumab
    Arm is closed.
    Other Name: AMG 386 (Trebananib); Trastuzumab (Herceptin)
  • Drug: T-DM1 and Pertuzumab
    Arm is closed.
    Other Name: T-DM1 (Trastuzumab emtansine); Pertuzumab (Perjeta)
  • Drug: Pertuzumab and Trastuzumab
    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
    Other Name: Pertuzumab (Perjeta); Trastuzumab (Herceptin)
  • Drug: Ganetespib
    Arm is closed.
  • Drug: ABT-888
    Arm is closed.
    Other Name: Veliparib
  • Drug: Neratinib
    Arm is closed.
  • Drug: PLX3397
    Arm is closed.
  • Drug: Pembrolizumab - 4 cycle
    Arm is closed.
  • Drug: Talazoparib plus Irinotecan
    Arm is closed.
  • Drug: Patritumab and Trastuzumab
    Arm is closed.
  • Drug: Pembrolizumab - 8 cycle
    Arm is closed.
  • Drug: SGN-LIV1A
    SGN-LIV1A: 2.5 mg/kg IV cycles 1,4,7,10 Doxorubicin + Cyclophosphamide: Cycles 13-16
  • Drug: Durvalumab plus Olaparib
    Arm is closed.
  • Drug: SD-101 + Pembrolizumab
    SD-101: IT injection 2 mg/ml (1 ml for T2 tumors, 2 ml for >T3 tumors) weekly x 4, then every 3 weeks x 2 cycles 1,2,3,4,7,10 Pembrolizumab: 200mg IV cycles 1,4,7,10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles
  • Drug: Tucatinib plus trastuzumab and pertuzumab
    Tucatinib: 300 mg PO BID 12 weeks CLOSED Tucatinib: 250 mg PO BID 12 weeks CLOSED Tucatinib adaptive: 150mg BID days 1-28, 250mg BID days 29-84 Trastuzumab: 4 mg/kg IV (loading dose) cycle 1; 2 mg/kg (thereafter) cycles 2-12 Pertuzumab: 840 mg IV (loading dose) cycle 1; 420 mg (thereafter) cycles 4, 7 and 10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles
  • Drug: Cemiplimab
    Cemiplimab: 350 mg q3w X 12 weeks IV cycles 1,4,7,10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles
  • Drug: Cemiplimab plus REGN3767
    Cemiplimab: 350 mg q3w X 12 weeks IV cycles 1,4,7,10 REGN 3767: 1600 mg q3W X 12 weeks IV cycles 1,4,7,10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles
  • Drug: Trilaciclib with or without trastuzumab + pertuzumab

    Trilaciclib: 240 mg/m2 IV weekly cycle 1-16 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles

    For HER2+:

    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

    Other Name: Trilaciclib (G1T28); Pertuzumab (Perjeta); Trastuzumab (Herceptin)
  • Drug: SYD985 ([vic-]trastuzumab duocarmazine)
    SYD985: 1.2 mg/kg IV (q3w x 12 weeks) cycles 1,4,7,10 Doxorubicin + Cyclophosphamide: Cycles 13-16; Doxorubicin: 60 mg/m2 IV Every 2 or 3 weeks for 4 cycles; Cyclophosphamide: 600 mg/m2 IV Every 2 or 3 weeks for 4 cycles
  • Drug: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab

    For HER2+ Dostarlimab (TSR-042), 500 mg, IV, q3wks for wk 1, 4, 7, 10 Trastuzumab, 4 mg/kg cycle 1, then 2 mg/kg cycles 2-12 q1wk, IV, for wk1-12 Oral paclitaxel, 205 mg/m2, oral, daily for Three (3) days in a row each week for weeks 1-12 Oral encequidar, 15 mg, oral, daily for Three (3) days in a row each week for weeks 1-12 Carboplatin, AUC 1.5, IV, q1wk from wk1-12 Followed by Doxorubicin: 60 mg/m2, IV, every 2 or 3 weeks for 4 cycles Cyclophosphamide: 600 mg/m2, IV, every 2 or 3 weeks for 4 cycle

    For HER2- Dostarlimab (TSR-042), 500 mg, IV, q3wks for wk 1, 4, 7, 10 Oral paclitaxel, 205 mg/m2, oral, daily for Three (3) days in a row each week for weeks 1-12 Oral encequidar, 15 mg, oral, daily for Three (3) days in a row each week for weeks 1-12 Carboplatin, AUC 1.5, IV, q1wk from wk1-12 Followed by Doxorubicin: 60 mg/m2, IV, every 2 or 3 weeks for 4 cycles Cyclophosphamide: 600 mg/m2, IV, every 2 or 3 weeks for 4 cycle

    Other Name: Oral Paclitaxel + Encequidar (Oraxol); Dostarlimab (TSR-042); Trastuzumab (Herceptin)
  • Drug: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab

    For HER2+ Dostarlimab (TSR-042), 500 mg, IV, q3wks for wk 1, 4, 7, 10 Trastuzumab, 4 mg/kg cycle 1, then 2 mg/kg cycles 2-12 q1wk, IV, for wk1-12 Oral paclitaxel, 205 mg/m2, oral, daily for Three (3) days in a row each week for weeks 1-12 Oral encequidar, 15 mg, oral, daily for Three (3) days in a row each week for weeks 1-12 Followed by Doxorubicin: 60 mg/m2, IV, every 2 or 3 weeks for 4 cycles Cyclophosphamide: 600 mg/m2, IV, every 2 or 3 weeks for 4 cycle

    For HER2- Dostarlimab (TSR-042), 500 mg, IV, q3wks for wk 1, 4, 7, 10 Oral paclitaxel, 205 mg/m2, oral, daily for Three (3) days in a row each week for weeks 1-12 Oral encequidar, 15 mg, oral, daily for Three (3) days in a row each week for weeks 1-12 Followed by Doxorubicin: 60 mg/m2, IV, every 2 or 3 weeks for 4 cycles Cyclophosphamide: 600 mg/m2, IV, every 2 or 3 weeks for 4 cycle

    Other Name: Oral Paclitaxel + Encequidar (Oraxol); Dostarlimab (TSR-042); Trastuzumab (Herceptin)
Study Arms  ICMJE
  • Active Comparator: Standard Therapy
    Paclitaxel, Herceptin followed by Doxorubicin and Cyclophosphamide treatment depending on HR/HER-2 status.
    Intervention: Drug: Standard Therapy
  • Experimental: AMG 386 with or without Trastuzumab
    Arm is closed.
    Interventions:
    • Drug: AMG 386 with or without Trastuzumab
    • Drug: AMG 386 and Trastuzumab
  • AMG 479 plus Metformin
    Arm is closed.
    Intervention: Drug: AMG 479 (Ganitumab) plus Metformin
  • Experimental: MK-2206 with or without Trastuzumab
    Arm is closed.
    Intervention: Drug: MK-2206 with or without Trastuzumab
  • Experimental: T-DM1 and Pertuzumab
    Arm is closed.
    Intervention: Drug: T-DM1 and Pertuzumab
  • Active Comparator: Pertuzumab and Trastuzumab
    Novel Control Investigational Agent
    Intervention: Drug: Pertuzumab and Trastuzumab
  • Experimental: Ganetespib
    Arm is closed.
    Intervention: Drug: Ganetespib
  • ABT-888
    Arm is closed.
    Intervention: Drug: ABT-888
  • Neratinib
    Arm is closed.
    Intervention: Drug: Neratinib
  • Experimental: PLX3397
    Arm is closed.
    Intervention: Drug: PLX3397
  • Experimental: Pembrolizumab 4 cycle
    Arm is closed.
    Intervention: Drug: Pembrolizumab - 4 cycle
  • Experimental: Talazoparib plus Irinotecan
    Arm is closed.
    Intervention: Drug: Talazoparib plus Irinotecan
  • Experimental: Patritumab with or without Trastuzumab
    Arm is closed.
    Intervention: Drug: Patritumab and Trastuzumab
  • Experimental: Pembrolizumab 8 cycle
    Arm is closed.
    Intervention: Drug: Pembrolizumab - 8 cycle
  • Experimental: SGN-LIV1A
    Novel Investigational Agent
    Intervention: Drug: SGN-LIV1A
  • Experimental: Durvalumab plus Olaparib
    Arm is closed.
    Intervention: Drug: Durvalumab plus Olaparib
  • Experimental: SD-101 + Pembrolizumab
    Novel Investigational Agent
    Intervention: Drug: SD-101 + Pembrolizumab
  • Experimental: Tucatinib
    Novel Investigational Agent
    Intervention: Drug: Tucatinib plus trastuzumab and pertuzumab
  • Experimental: Cemiplimab
    Novel Investigational Agent
    Intervention: Drug: Cemiplimab
  • Experimental: Cemiplimab plus REGN3767
    Novel Investigational Agent
    Intervention: Drug: Cemiplimab plus REGN3767
  • Experimental: Trilaciclib with or without trastuzumab + pertuzumab
    Novel Investigational Agent
    Intervention: Drug: Trilaciclib with or without trastuzumab + pertuzumab
  • Experimental: SYD985 ([vic-]trastuzumab duocarmazine)
    Novel Investigational Agent
    Intervention: Drug: SYD985 ([vic-]trastuzumab duocarmazine)
  • Experimental: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab
    Novel Investigational Agent
    Intervention: Drug: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab
  • Experimental: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab
    Novel Investigational Agent
    Intervention: Drug: Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 6, 2020)
4000
Original Estimated Enrollment  ICMJE
 (submitted: January 4, 2010)
800
Estimated Study Completion Date  ICMJE December 2026
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Meera Bose 415-514-6878 ispyadmin@ucsf.edu
Contact: Smita Asare smita.asare@ispy2.org
Listed Location Countries  ICMJE United States
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT01042379
Other Study ID Numbers  ICMJE 097517
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party QuantumLeap Healthcare Collaborative
Study Sponsor  ICMJE QuantumLeap Healthcare Collaborative
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Laura Esserman, MD, MBA University of California, San Francisco
PRS Account QuantumLeap Healthcare Collaborative
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP