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I-SPY 2 TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer (I-SPY 2)

This study is currently recruiting participants.
Verified October 2017 by QuantumLeap Healthcare Collaborative
Sponsor:
ClinicalTrials.gov Identifier:
NCT01042379
First Posted: January 5, 2010
Last Update Posted: October 20, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
QuantumLeap Healthcare Collaborative
  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.

Condition Intervention Phase
Breast Neoplasms Breast Cancer Breast Tumors Drug: Standard Therapy Drug: AMG 386 with or without Trastuzumab Drug: AMG 479 (Ganitumab) plus Metformin Drug: MK-2206 with or without Trastuzumab Drug: AMG 386 and Trastuzumab Drug: T-DM1 and Pertuzumab Drug: Pertuzumab and Trastuzumab Drug: Ganetespib Drug: ABT-888 Drug: Neratinib Drug: PLX3397 Drug: Pembrolizumab - 4 cycle Drug: Talazoparib plus Irinotecan Drug: Patritumab and Trastuzumab Drug: Pembrolizumab - 8 cycle Drug: SGN-LIV1A Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: I-SPY 2 Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)

Resource links provided by NLM:


Further study details as provided by QuantumLeap Healthcare Collaborative:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 1920
Study Start Date: March 2010
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: AMG 386 (Trebananib); (Trastuzumab) Herceptin
Drug: AMG 386 and Trastuzumab
Arm is closed.
Other Name: AMG 386 (Trebananib); Trastuzumab (Herceptin)
AMG 479 plus Metformin
Arm is closed.
Drug: AMG 479 (Ganitumab) plus Metformin
Arm is closed.
Other Name: Ganitumab
Experimental: MK-2206 with or without Trastuzumab
Arm is closed.
Drug: MK-2206 with or without Trastuzumab
Arm is closed.
Other Name: (Trastuzumab) Herceptin
Experimental: T-DM1 and Pertuzumab
Arm is closed.
Drug: T-DM1 and Pertuzumab
Arm is closed.
Other Name: T-DM1 (Trastuzumab emtansine); Pertuzumab (Perjeta)
Active Comparator: Pertuzumab and Trastuzumab
Novel Control Investigational Agent
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)
Experimental: Ganetespib
Arm is closed.
Drug: Ganetespib
Arm is closed.
ABT-888
Arm is closed.
Drug: ABT-888
Arm is closed.
Other Name: Veliparib
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
Novel Investigational Agent
Drug: Patritumab and Trastuzumab
Patritumab: 18 mg/kg loading of patritumab (cycle 1) followed by 9 mg/kg thereafter (cycles 4, 7, 10) post-randomization; Trastuzumab: 4 mg/kg (loading dose) cycle 1 and 2 mg/kg cycles (weeks 2-12) post-randomization Doxorubicin + Cyclophosphamide: Cycles 13-16
Experimental: Pembrolizumab 8 cycle
Novel Investigational Agent
Drug: Pembrolizumab - 8 cycle
Pembrolizumab: 200mg IV cycles 1,4,7,10,13,14,15,16 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16
Experimental: SGN-LIV1A
Novel Investigational Agent
Drug: SGN-LIV1A
SGN-LIV1A: 2.5 mg/kg IV cycles 1,4,7,10 Doxorubicin + Cyclophosphamide: Cycles 13-16

Detailed Description:
I-SPY 2 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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01042379


Contacts
Contact: Ruby Singhrao, MS, CCRP 415-353-4171 ruby.singhrao@ucsf.edu
Contact: Smita Asare smita.asare@ispy2.org

  Show 24 Study Locations
Sponsors and Collaborators
QuantumLeap Healthcare Collaborative
Investigators
Principal Investigator: Laura Esserman, MD, MBA University of California, San Francisco (UCSF)
  More Information

Additional Information:
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: QuantumLeap Healthcare Collaborative
ClinicalTrials.gov Identifier: NCT01042379     History of Changes
Other Study ID Numbers: 097517
First Submitted: December 31, 2009
First Posted: January 5, 2010
Last Update Posted: October 20, 2017
Last Verified: October 2017

Keywords provided by QuantumLeap Healthcare Collaborative:
I-SPY 2
Neoadjuvant
Breast
Cancer
Neoplasm
Adaptive
pCR
Pathologic Complete Response
Biomarkers signature
MRI Volume

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Irinotecan
Ado-trastuzumab emtansine
Liposomal doxorubicin
Pembrolizumab
Pertuzumab
Veliparib
Trebananib
Talazoparib
Albumin-Bound Paclitaxel
Cyclophosphamide
Doxorubicin
Trastuzumab
Metformin
Antibodies, Monoclonal
Immunoconjugates
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs
Immunosuppressive Agents