Working… Menu

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

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. Identifier: NCT01042379
Recruitment Status : Recruiting
First Posted : January 5, 2010
Last Update Posted : May 16, 2019
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment 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 Drug: Durvalumab plus Olaparib Drug: SD-101 + Pembrolizumab Drug: Tucatinib Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1920 participants
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)
Study Start Date : March 2010
Estimated Primary Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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.

Arm is closed.
Drug: ABT-888
Arm is closed.
Other Name: Veliparib

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
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

Experimental: SGN-LIV1A
Novel Investigational Agent
SGN-LIV1A: 2.5 mg/kg IV cycles 1,4,7,10 Doxorubicin + Cyclophosphamide: Cycles 13-16

Experimental: Durvalumab plus Olaparib
Novel Investigational Agent
Drug: Durvalumab plus Olaparib
Durvalumab: 1500 mg IV cycles 1, 5 and 9 Olaparib: 200mg cycles 1-11, daily Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16

Experimental: SD-101 + Pembrolizumab
Novel Investigational Agent
Drug: SD-101 + Pembrolizumab
SD-101: 2 mg/ml cycles 1,2,3,4,7,10 Pembrolizumab: 200mg cycles 1,4,7,10 Paclitaxel: 80 mg/m2 IV cycles 1-12 Doxorubicin + Cyclophosphamide: Cycles 13-16

Experimental: Tucatinib
Novel Investigational Agent
Drug: Tucatinib
Tucatinib: 300mg BID cycles 1-12 Trastuzumab: 4 mg/kg (loading dose) cycle 1, 2 mg/kg (thereafter) cycles 2-12 Pertuzumab: 840 mg (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

Primary Outcome Measures :
  1. 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 :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. MRI Volume [ Time Frame: Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery ]

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.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
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

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 identifier (NCT number): NCT01042379

Layout table for location contacts
Contact: Ruby Singhrao, MS, CCRP 415-353-4171
Contact: Smita Asare

  Hide Study Locations
Layout table for location information
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Valerie Caterinicchia, RN, BSN    205-934-5367   
Principal Investigator: Andres Forero, MD         
United States, Arizona
Mayo Clinic - Scottsdale Active, not recruiting
Scottsdale, Arizona, United States, 85259
University of Arizona Active, not recruiting
Tucson, Arizona, United States, 85724
United States, California
University of California San Diego Recruiting
La Jolla, California, United States, 92093-0698
Contact: Michael Krak    858-534-5532   
Contact    858-822-5354   
Principal Investigator: Anne Wallace, MD         
University of Southern California Active, not recruiting
Los Angeles, California, United States, 90033
University of California San Francisco (UCSF) Recruiting
San Francisco, California, United States, 94115
Contact    877-827-3222      
Principal Investigator: Amy Jo Chien, MD         
United States, Colorado
University of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Tessa Mcspadden    720-848-0609   
Principal Investigator: Anthony Elias, MD         
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06510
Contact: Trisha Burello, MS    203-737-2848   
Sub-Investigator: Tara Snaft, MD         
Sub-Investigator: Lajos Pusztai, MD         
United States, District of Columbia
Georgetown University Medical Center Recruiting
Washington, District of Columbia, United States, 20007
Contact: Minetta Liu, MD    202-444-3677   
Principal Investigator: Claudine Isaacs, MD         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Katrina Dawson, BS, CCRP    813-745-5975   
Principal Investigator: Susan Minton, MD         
United States, Georgia
Emory University Active, not recruiting
Atlanta, Georgia, United States, 30322
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Vanessa Falero    404-727-3449   
Principal Investigator: Jane Meisel, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60453
Contact: Simona Olberkyte    773-834-9774   
Principal Investigator: Rita Nanda, MD         
Loyola University Recruiting
Maywood, Illinois, United States, 60153
Contact: Kathy Czaplicki    708-327-3322   
Principal Investigator: Kathy Albain, MD         
United States, Kansas
University of Kansas Active, not recruiting
Westwood, Kansas, United States, 66205
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Anne Janisch, RN MSN    612-626-5369   
Principal Investigator: Doug Yee, MD         
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact    507-538-7623      
Principal Investigator: Judy C Boughey, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States
Contact: Leslie Segal, MPH    212-304-6346   
Sub-Investigator: Kevin Kalinsky, MD         
United States, North Carolina
Wake Forest Baptist Comprehensive Cancer Center Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Angela Howell, MD    336-716-5440   
Principal Investigator: Alexandra Thomas, MD         
United States, Oregon
Oregon Health & Science Institute (OHSU) Recruiting
Portland, Oregon, United States, 97239
Contact: Jenna Bucher, BS    503-418-9736   
Principal Investigator: Kathleen Y Kemmer, MD         
United States, Pennsylvania
University of Pennsylvania (U Penn) Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Lauren Bayne    215-349-5398   
Principal Investigator: Amy Clark, MD         
United States, Texas
University of Texas, Southwestern Medical Center Active, not recruiting
Dallas, Texas, United States, 75390-9155
University of Texas, M.D. Anderson Cancer Center Active, not recruiting
Houston, Texas, United States, 77230-1439
United States, Virginia
Inova Health System Active, not recruiting
Falls Church, Virginia, United States, 22042
United States, Washington
Swedish Cancer Institute Active, not recruiting
Seattle, Washington, United States, 98104
University of Washington Active, not recruiting
Seattle, Washington, United States, 98115
Sponsors and Collaborators
QuantumLeap Healthcare Collaborative
Layout table for investigator information
Principal Investigator: Laura Esserman, MD, MBA University of California, San Francisco

Additional Information:
Publications of Results:

Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):

Layout table for additonal information
Responsible Party: QuantumLeap Healthcare Collaborative Identifier: NCT01042379     History of Changes
Other Study ID Numbers: 097517
First Posted: January 5, 2010    Key Record Dates
Last Update Posted: May 16, 2019
Last Verified: May 2019
Keywords provided by QuantumLeap Healthcare Collaborative:
Pathologic Complete Response
Biomarkers signature
MRI Volume
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Ado-trastuzumab emtansine
Albumin-Bound Paclitaxel
Liposomal doxorubicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs
Immunosuppressive Agents