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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by QuantumLeap Healthcare Collaborative
Information provided by (Responsible Party):
QuantumLeap Healthcare Collaborative
ClinicalTrials.gov Identifier:
First received: December 31, 2009
Last updated: February 20, 2014
Last verified: February 2014

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
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
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • MRV [ Time Frame: Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 800
Study Start Date: March 2010
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: February 2014 (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
Experimental: AMG 386
Novel investigational agent
Drug: AMG 386
15 mg/kg IV every week during 12 weekly treatment cycles post-randomization
Experimental: AMG 479 (Ganitumab) plus Metformin
Novel investigational agent
Drug: AMG 479 (Ganitumab) plus Metformin
AMG 479 (Ganitumab) 12 mg/kg IV every 2 weeks during 12 week treatment cycle post-randomization; Metformin: 850 mg po every week during 12 weekly treatment cycles post-randomization
Other Name: Ganitumab
Experimental: MK-2206 with or without Trastuzumab
Novel investigational agent
Drug: MK-2206 with or without Trastuzumab
MK-2206: 135 mg every week during 12 weekly treatment cycles post-randomization; Trastuzumab: 4 mg/kg (loading dose) week 1 and 2 mg/kg weekly (weeks 2-12) post-randomization
Experimental: AMG 386 and Trastuzumab
Novel Investigational Agent
Drug: AMG 386 and Trastuzumab
AMG 386: 15 mg/kg IV every week during 12 weekly treatment cycles post-randomization; Trastuzumab: 4 mg/kg (loading dose) week 1 and 2 mg/kg weekly (weeks 2-12) post-randomization
Experimental: T-DM1 and Pertuzumab
Novel Investigational Agent
Drug: T-DM1 and Pertuzumab
T-DM1: 3.6 mg/kg IV every 2 weeks (weeks 1, 4, 7, 10) post-randomization; Pertuzumab: 840 mg IV (loading dose) week 1 and 420 mg every 3 weeks (weeks 4, 7, 10) post-randomization
Experimental: Pertuzumab and Trastuzumab
Novel 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

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 are graduated or dropped.


Ages Eligible for Study:   18 Years and older
Genders 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01042379

Contact: Meredith Buxton, MPhil, MPH 415-353-7357 meredith.buxton@ucsfmedctr.org

United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Valerie Caterinicchia, RN, BSN    205-934-5367    val7@uab.edu   
Principal Investigator: Andres Forero, MD         
United States, Arizona
Mayo Clinic - Scottsdale Active, not recruiting
Scottsdale, Arizona, United States, 85259
University of Arizona Recruiting
Tucson, Arizona, United States, 85724
Contact: Amy S Bauland    520-694-0859    abauland@azcc.arizona.edu   
Principal Investigator: Rebecca Viscusi, MD         
United States, California
University of California San Diego Recruiting
La Jolla, California, United States, 92093-0698
Contact: Cynthia Meyer    858-822-6575    cjmeyer@ucsd.edu   
Contact    858-822-5354    CancerCTO@ucsd.edu   
Principal Investigator: Anne Wallace, MD         
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Contact: Debu Tripathy, MD    323-865-3900    Tripathy@usc.edu   
Contact: Kristy Watkins, RN    323-865-0452    Watkins_K@ccnt.usc.edu   
Principal Investigator: Debasish Tripathy, MD         
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    tessa.mcspadden@ucdenver.edu   
Principal Investigator: Anthony Elias, 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    Liumc@georgetown.edu   
Principal Investigator: Claudine Isaacs, MD         
United States, Georgia
Emory University Active, not recruiting
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60453
Contact: Jean Gibson    773-834-2167    jgibson@medicine.bsd.uchicago.edu   
Principal Investigator: Rita Nanda, MD         
Loyola University Recruiting
Maywood, Illinois, United States, 60153
Contact: Kathy Czaplicki    708-327-3322    kczapli@lumc.edu   
Contact: Agnes Natonton    708-327-2237    anatont@lumc.edu   
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: Charlotte Smith    612-625-9498    Smit4652@umn.edu   
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, Oregon
Oregon Health & Science Institute (OHSU) Recruiting
Portland, Oregon, United States, 97239
Contact: Deirdre Nauman, BSN,CCRP    503-494-3078    naumand@ohsu.edu   
Principal Investigator: Stephen Y Chui, MD         
United States, Pennsylvania
University of Pennsylvania (U Penn) Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Luke Velders    215-615-6821    Luke.Velders@uphs.upenn.edu   
Principal Investigator: Angela DeMichele, MD         
United States, Texas
University of Texas, Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390-9155
Contact: Barabara Staves, BS    214-648-1988    barbara.staves@utsouthwestern.edu   
Contact: Vanessa Tagoe, MA, CCRC    214-648-7020    Vanessa.Tagoe@utsouthwestern.edu   
Principal Investigator: David Euhus, MD         
University of Texas, M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77230-1439
Contact: Cara Dunlap, RN    713-745-8748    CLDunlap@mdanderson.org   
Principal Investigator: Stacy Moulder, MD, MSCI         
United States, Virginia
Inova Health System Recruiting
Falls Church, Virginia, United States, 22042
Contact: Alyssa Bruflodt    703-776-3565    Alyssa.Bruflodt@inova.org   
Principal Investigator: Kirsten Edmiston, MD, FACS         
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 98104
Contact: Barry Boatman, RN    206-215-3086    CancerResearch@swedish.org   
Principal Investigator: Hank Kaplan, MD         
Principal Investigator: Erin Ellis, MD         
University of Washington Recruiting
Seattle, Washington, United States, 98115
Principal Investigator: Larissa Korde, MD, MPH         
Sponsors and Collaborators
QuantumLeap Healthcare Collaborative
Principal Investigator: Laura Esserman, MD, MBA University of California, San Francisco (UCSF)
  More Information

Additional Information:
Responsible Party: QuantumLeap Healthcare Collaborative
ClinicalTrials.gov Identifier: NCT01042379     History of Changes
Other Study ID Numbers: 097517
Study First Received: December 31, 2009
Last Updated: February 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by QuantumLeap Healthcare Collaborative:
Pathologic Complete Response
Biomarkers signature

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 16, 2014