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

Purpose

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.

Conditions

  • 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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Standard Therapy 		Paclitaxel, Herceptin followed by Doxorubicin and Cyclophosphamide treatment depending on HR/HER-2 status.
  • 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 names:
    • Paclitaxel (Taxol); Doxorubicin (Adriamycin)
Experimental
AMG 386 with or without Trastuzumab 		Arm is closed.
  • Drug: AMG 386 with or without Trastuzumab
    Arm is closed.
    Other names:
    • AMG 386 (Trebananib); (Trastuzumab) Herceptin
  • Drug: AMG 386 and Trastuzumab
    Arm is closed.
    Other names:
    • AMG 386 (Trebananib); Trastuzumab (Herceptin)
Other
AMG 479 plus Metformin 		Arm is closed.
  • Drug: AMG 479 (Ganitumab) plus Metformin
    Arm is closed.
    Other names:
    • Ganitumab
Experimental
MK-2206 with or without Trastuzumab 		Arm is closed.
  • Drug: MK-2206 with or without Trastuzumab
    Arm is closed.
    Other names:
    • (Trastuzumab) Herceptin
Experimental
T-DM1 and Pertuzumab 		Arm is closed.
  • Drug: T-DM1 and Pertuzumab
    Arm is closed.
    Other names:
    • T-DM1 (Trastuzumab emtansine); Pertuzumab (Perjeta)
Active Comparator
Pertuzumab and Trastuzumab 		Novel Control Investigational Agent. Arm is closed.
  • 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 names:
    • Pertuzumab (Perjeta); Trastuzumab (Herceptin)
Experimental
Ganetespib 		Arm is closed.
  • Drug: Ganetespib
    Arm is closed.
Other
ABT-888 		Arm is closed.
  • Drug: ABT-888
    Arm is closed.
    Other names:
    • Veliparib
Other
Neratinib 		Arm is closed.
  • Drug: Neratinib
    Arm is closed.
Experimental
PLX3397 		Arm is closed.
  • Drug: PLX3397
    Arm is closed.
Experimental
Pembrolizumab 4 cycle 		Arm is closed.
  • Drug: Pembrolizumab - 4 cycle
    Arm is closed.
Experimental
Talazoparib plus Irinotecan 		Arm is closed.
  • Drug: Talazoparib plus Irinotecan
    Arm is closed.
Experimental
Patritumab with or without Trastuzumab 		Arm is closed.
  • Drug: Patritumab and Trastuzumab
    Arm is closed.
Experimental
Pembrolizumab 8 cycle 		Arm is closed.
  • Drug: Pembrolizumab - 8 cycle
    Arm is closed.
Experimental
SGN-LIV1A 		Arm is closed.
  • Drug: SGN-LIV1A
    Arm is closed. SGN-LIV1A: 2.5 mg/kg IV cycles 1,4,7,10 Doxorubicin + Cyclophosphamide: Cycles 13-16
Experimental
Durvalumab plus Olaparib 		Arm is closed.
  • Drug: Durvalumab plus Olaparib
    Arm is closed.
Experimental
SD-101 + Pembrolizumab 		Arm is closed.
  • Drug: SD-101 + Pembrolizumab
    Arm is closed. 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
Experimental
Tucatinib 		Arm is closed.
  • Drug: Tucatinib plus trastuzumab and pertuzumab
    Arm is closed. 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
Experimental
Cemiplimab 		Novel Investigational Agent. Arm is closed.
  • 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: ARX788 + Cemiplimab
    ARX788, 1.5 mg/kg Q3W, IV for 12 weeks Cemiplimab, 350 mg Q3W, IV for 12 weeks
  • Drug: VV1 + Cemiplimab
    VV1, 3x10^9 TCID50 once (day-8), Intra-tumoral injection Cemiplimab, 350 mg Q3W, IV for 12 weeks
    Other names:
    • VOYAGER V1™
    • VSV-IFNβ-NIS
  • Drug: Sarilumab + Cemiplimab + Paclitaxel
    Sarilumab: 200mg Subcutaneous injection Q2W for 12 weeks Cemiplimab: 350mg IV Q3W for 12 weeks Paclitaxel: 80 mg/m2 IV QW for 12 weeks
Experimental
Cemiplimab plus REGN3767 		Novel Investigational Agent. Arm is closed.
  • 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
Experimental
Trilaciclib with or without trastuzumab + pertuzumab 		Novel Investigational Agent. Arm is closed.
  • 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 names:
    • Trilaciclib (G1T28); Pertuzumab (Perjeta); Trastuzumab (Herceptin)
Experimental
SYD985 ([vic-]trastuzumab duocarmazine) 		Novel Investigational Agent. Arm is closed.
  • 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
Experimental
Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) + Carboplatin with or without trastuzumab 		Novel Investigational Agent. Arm is closed.
  • 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 names:
    • Oral Paclitaxel + Encequidar (Oraxol); Dostarlimab (TSR-042); Trastuzumab (Herceptin)
Experimental
Oral Paclitaxel + Encequidar + Dostarlimab (TSR-042) with or without trastuzumab 		Novel Investigational Agent. Arm is closed.
  • 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 names:
    • Oral Paclitaxel + Encequidar (Oraxol); Dostarlimab (TSR-042); Trastuzumab (Herceptin)
Experimental
Endocrine Optimization Pilot: Amcenestrant Monotherapy 		Novel Investigational Agent. Arm is closed.
  • Drug: Amcenestrant
    Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks
    Other names:
    • SAR439859
Experimental
Endocrine Optimization Pilot: Amcenestrant + Abemaciclib 		Novel Investigational Agent. Arm is closed.
  • Drug: Amcenestrant + Abemaciclib
    Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks Abemaciclib (Verzenio), 150mg BID, p.o., for 24 weeks
    Other names:
    • Amcenestrant (SAR439859), Abemaciclib (Verzenio)
Experimental
Endocrine Optimization Pilot: Amcenestrant + Letrozole 		Novel Investigational Agent. Arm is closed.
  • Drug: Amcenestrant + Letrozole
    Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks Letrozole (Femara), 2.5mg QD, p.o., for 24 weeks
    Other names:
    • Amcenestrant (SAR439859), Letrozole (Femara)
Experimental
ARX788 in Block A and followed by SOC in Block B 		Novel investigational Agent followed by SOC
  • Drug: ARX788
    ARX788, 1.5 mg/kg Q3W, IV for 12 weeks
Experimental
ARX788 + Cemiplimab in Block A and followed by SOC in Block B 		Novel investigational Agent followed by SOC. Arm is closed.
  • Drug: ARX788 + Cemiplimab
    ARX788, 1.5 mg/kg Q3W, IV for 12 weeks Cemiplimab, 350 mg Q3W, IV for 12 weeks
Experimental
VSV-IFNβ-NIS (VOYAGER V1™; VV1) + Cemiplimab in Block A and followed by SOC in block B 		Novel investigational Agent followed by SOC
  • Drug: VV1 + Cemiplimab
    VV1, 3x10^9 TCID50 once (day-8), Intra-tumoral injection Cemiplimab, 350 mg Q3W, IV for 12 weeks
    Other names:
    • VOYAGER V1™
    • VSV-IFNβ-NIS
Experimental
Datopotamab Deruxtecan in Block A and followed by SOC in block B 		Novel investigational Agent followed by SOC
  • Drug: Datopotamab deruxtecan
    Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks
    Other names:
    • Dato-DXd
Experimental
Datopotamab Deruxtecan + Durvalumab in Block A and followed by SOC in block B 		Novel investigational Agent followed by SOC
  • Drug: Datopotamab deruxtecan + Durvalumab
    Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks Durvalumab, 1120 mg Q3W, IV for 12 weeks
    Other names:
    • Dato-DXd
Experimental
Zanidatamab in Block A and followed by SOC in block B 		Novel investigational Agent followed by SOC
  • Drug: Zanidatamab
    Zanidatamab: Flat dose of 1,200mg Q2W for 12 weeks
Experimental
Endocrine Optimization Pilot: Lasofoxifene 		Novel investigational Agent
  • Drug: Lasofoxifene
    Lasofoxifene: 5.0 mg QD, p.o., for 24 weeks
Experimental
Endocrine Optimization Pilot: (Z)-Endoxifen 		Novel investigational Agent
  • Drug: Z-endoxifen
    Z-endoxifen: 10 mg QD, p.o., for 24 weeks
  • Drug: Endoxifen + Abemaciclib
    Z-endoxifen: 80 mg QD, p.o., for 24 weeks Abemaciclib: 150 mg BID, p.o, for 20 weeks
Experimental
Endocrine Optimization Pilot: ARV-471 		Novel investigational Agent
  • Drug: ARV-471
    ARV-471: 200 mg QD, p.o, for 24 weeks
  • Drug: ARV-471 + Letrozole
    ARV-471: 200 mg QD, p.o, for 24 weeks Letrozole: 2.5 mg QD, p.o, for 24 weeks
  • Drug: ARV-471 + Abemaciclib
    ARV-471: 200 mg QD, p.o, for 24 weeks Abemaciclib: 150 mg BID, p.o, for 24 weeks
Experimental
Endocrine Optimization Pilot: ARV-471 + Letrozole 		Novel investigational Agent
  • Drug: ARV-471 + Letrozole
    ARV-471: 200 mg QD, p.o, for 24 weeks Letrozole: 2.5 mg QD, p.o, for 24 weeks
Experimental
Endocrine Optimization Pilot: ARV-471 + Abemaciclib 		Novel investigational Agent
  • Drug: ARV-471 + Abemaciclib
    ARV-471: 200 mg QD, p.o, for 24 weeks Abemaciclib: 150 mg BID, p.o, for 24 weeks
Experimental
Endocrine Optimization Pilot: (Z)-Endoxifen + Abemaciclib 		Novel investigational Agent
  • Drug: Endoxifen + Abemaciclib
    Z-endoxifen: 80 mg QD, p.o., for 24 weeks Abemaciclib: 150 mg BID, p.o, for 20 weeks
Experimental
Rilvegostomig + TDXd in Block A and followed by SOC in Block B 		Novel investigational Agent
  • Drug: Rilvegostomig + TDXd
    Rilvegostomig: 750mg IV Q3W for 12 weeks TDXd: 5.4 mg/kg IV Q3W for 12 weeks
Experimental
DAN222 + Niraparib in Block A and followed by SOC in Block B 		Novel investigational Agent
  • Drug: Dan222 + Niraparib
    DAN222: 8mg/m2 IV QW for 12 weeks Niraparib: 200mg QD p.p., 12 weeks
Experimental
Sarilumab + Cemiplimab + Paclitaxel in Block B followed by SOC Block C 		Novel investigational Agent
  • Drug: Sarilumab + Cemiplimab + Paclitaxel
    Sarilumab: 200mg Subcutaneous injection Q2W for 12 weeks Cemiplimab: 350mg IV Q3W for 12 weeks Paclitaxel: 80 mg/m2 IV QW for 12 weeks

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35294

More Details

Status
Recruiting
Sponsor
QuantumLeap Healthcare Collaborative

Study Contact

Won Chang
(855) 866-0505
w.chang@quantumleaphealth.org

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.