NCT01042379

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

Official Title:

I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)

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.

Eligibility

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

Disease(s) and\or Condition(s)

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

Primary Purpose
  • TREATMENT
Intervention/Treatment
    • Type: DRUG
    • Name: Standard Therapy
    • Description: 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
    • Arm Group Labels: Standard Therapy
    • Type: DRUG
    • Name: AMG 386 with or without Trastuzumab
    • Description: Arm is closed.
    • Arm Group Labels: AMG 386 with or without Trastuzumab
    • Type: DRUG
    • Name: AMG 479 (Ganitumab) plus Metformin
    • Description: Arm is closed.
    • Arm Group Labels: AMG 479 plus Metformin
    • Type: DRUG
    • Name: MK-2206 with or without Trastuzumab
    • Description: Arm is closed.
    • Arm Group Labels: MK-2206 with or without Trastuzumab
    • Type: DRUG
    • Name: AMG 386 and Trastuzumab
    • Description: Arm is closed.
    • Arm Group Labels: AMG 386 with or without Trastuzumab
    • Type: DRUG
    • Name: T-DM1 and Pertuzumab
    • Description: Arm is closed.
    • Arm Group Labels: T-DM1 and Pertuzumab
    • Type: DRUG
    • Name: Pertuzumab and Trastuzumab
    • Description: 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
    • Arm Group Labels: Pertuzumab and Trastuzumab
    • Type: DRUG
    • Name: Ganetespib
    • Description: Arm is closed.
    • Arm Group Labels: Ganetespib
    • Type: DRUG
    • Name: ABT-888
    • Description: Arm is closed.
    • Arm Group Labels: ABT-888
    • Type: DRUG
    • Name: Neratinib
    • Description: Arm is closed.
    • Arm Group Labels: Neratinib
    • Type: DRUG
    • Name: PLX3397
    • Description: Arm is closed.
    • Arm Group Labels: PLX3397
    • Type: DRUG
    • Name: Pembrolizumab - 4 cycle
    • Description: Arm is closed.
    • Arm Group Labels: Pembrolizumab 4 cycle
    • Type: DRUG
    • Name: Talazoparib plus Irinotecan
    • Description: Arm is closed.
    • Arm Group Labels: Talazoparib plus Irinotecan
    • Type: DRUG
    • Name: Patritumab and Trastuzumab
    • Description: Arm is closed.
    • Arm Group Labels: Patritumab with or without Trastuzumab
    • Type: DRUG
    • Name: Pembrolizumab - 8 cycle
    • Description: Arm is closed.
    • Arm Group Labels: Pembrolizumab 8 cycle
    • Type: DRUG
    • Name: SGN-LIV1A
    • Description: Arm is closed. SGN-LIV1A: 2.5 mg/kg IV cycles 1,4,7,10 Doxorubicin + Cyclophosphamide: Cycles 13-16
    • Arm Group Labels: SGN-LIV1A
    • Type: DRUG
    • Name: Durvalumab plus Olaparib
    • Description: Arm is closed.
    • Arm Group Labels: Durvalumab plus Olaparib
    • Type:
    • Name:
    • Description:
    • Arm Group Labels:
    • Type: DRUG
    • Name: Tucatinib plus trastuzumab and pertuzumab
    • Description: 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
    • Arm Group Labels: Tucatinib
    • Type: DRUG
    • Name: Cemiplimab
    • Description: 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
    • Arm Group Labels: Cemiplimab
    • Type: DRUG
    • Name: Cemiplimab plus REGN3767
    • Description: 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
    • Arm Group Labels: Cemiplimab plus REGN3767
    • Type:
    • Name:
    • Description:
    • Arm Group Labels:
    • Type: DRUG
    • Name: SYD985 ([vic-]trastuzumab duocarmazine)
    • Description: 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
    • Arm Group Labels: SYD985 ([vic-]trastuzumab duocarmazine)
    • Type:
    • Name:
    • Description:
    • Arm Group Labels:
    • Type:
    • Name:
    • Description:
    • Arm Group Labels:
    • Type: DRUG
    • Name: Amcenestrant
    • Description: Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks
    • Arm Group Labels: Endocrine Optimization Pilot: Amcenestrant Monotherapy
    • Type: DRUG
    • Name: Amcenestrant + Abemaciclib
    • Description: Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks Abemaciclib (Verzenio), 150mg BID, p.o., for 24 weeks
    • Arm Group Labels: Endocrine Optimization Pilot: Amcenestrant + Abemaciclib
    • Type: DRUG
    • Name: Amcenestrant + Letrozole
    • Description: Amcenestrant (SAR439859), 200mg QD, p.o., for 24 weeks Letrozole (Femara), 2.5mg QD, p.o., for 24 weeks
    • Arm Group Labels: Endocrine Optimization Pilot: Amcenestrant + Letrozole
    • Type: DRUG
    • Name: ARX788
    • Description: ARX788, 1.5 mg/kg Q3W, IV for 12 weeks
    • Arm Group Labels: ARX788 in Block A and followed by SOC in Block B
    • Type: DRUG
    • Name: ARX788 + Cemiplimab
    • Description: ARX788, 1.5 mg/kg Q3W, IV for 12 weeks Cemiplimab, 350 mg Q3W, IV for 12 weeks
    • Arm Group Labels: ARX788 + Cemiplimab in Block A and followed by SOC in Block B
    • Type: DRUG
    • Name: VV1 + Cemiplimab
    • Description: VV1, 3x10\^9 TCID50 once (day-8), Intra-tumoral injection Cemiplimab, 350 mg Q3W, IV for 12 weeks
    • Arm Group Labels: VSV-IFNβ-NIS (VOYAGER V1™; VV1) + Cemiplimab in Block A and followed by SOC in block B
    • Type: DRUG
    • Name: Datopotamab deruxtecan
    • Description: Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks
    • Arm Group Labels: Datopotamab Deruxtecan in Block A and followed by SOC in block B
    • Type: DRUG
    • Name: Datopotamab deruxtecan + Durvalumab
    • Description: Dato-DXd, 6 mg/kg Q3W, IV for 12 weeks Durvalumab, 1120 mg Q3W, IV for 12 weeks
    • Arm Group Labels: Datopotamab Deruxtecan + Durvalumab in Block A and followed by SOC in block B
    • Type: DRUG
    • Name: Zanidatamab
    • Description: Zanidatamab: Flat dose of 1,200mg Q2W for 12 weeks
    • Arm Group Labels: Zanidatamab in Block A and followed by SOC in block B
    • Type: DRUG
    • Name: Lasofoxifene
    • Description: Lasofoxifene: 5.0 mg QD, p.o., for 24 weeks
    • Arm Group Labels: Endocrine Optimization Pilot: Lasofoxifene
    • Type: DRUG
    • Name: Z-endoxifen
    • Description: Z-endoxifen: 10 mg QD, p.o., for 24 weeks
    • Arm Group Labels: Endocrine Optimization Pilot: (Z)-Endoxifen
    • Type: DRUG
    • Name: ARV-471
    • Description: ARV-471: 200 mg QD, p.o, for 24 weeks
    • Arm Group Labels: Endocrine Optimization Pilot: ARV-471
    • Type: DRUG
    • Name: ARV-471 + Letrozole
    • Description: ARV-471: 200 mg QD, p.o, for 24 weeks Letrozole: 2.5 mg QD, p.o, for 24 weeks
    • Arm Group Labels: Endocrine Optimization Pilot: ARV-471 + Letrozole
Sponsor
  • QuantumLeap Healthcare Collaborative