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

Status: Active


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 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

Locations & Contacts


University of Alabama at Birmingham Cancer Center
Status: Active
Contact: Valerie Caterinicchia
Phone: 205-934-5367
Email: val7@uab.edu


Los Angeles
USC / Norris Comprehensive Cancer Center
Status: Active
Name Not Available
San Diego
University of California San Diego
Status: Active
Contact: Michael Krak
Phone: 858-534-5532
Email: mkrak@ucsd.edu
San Francisco
UCSF Medical Center-Mount Zion
Status: Active
Contact: Amy Jo Chien
Phone: 877-827-3222


University of Colorado Hospital
Status: Temporarily closed to accrual
Contact: Tessa McSpadden
Phone: 720-848-0609
Email: tessa.mcspadden@ucdenver.edu


New Haven
Yale University
Status: Active
Contact: Trisha Burrello
Phone: 203-737-2848
Email: trisha.burrello@yale.edu

District of Columbia

MedStar Georgetown University Hospital
Status: Active
Name Not Available


Moffitt Cancer Center
Status: Active
Name Not Available


Emory University Hospital / Winship Cancer Institute
Status: Active
Name Not Available


University of Chicago Comprehensive Cancer Center
Status: Active
Contact: Simona Olberkyte
Phone: 773-834-9774
Email: solberkyte@medicine.bsd.uchicago.edu


University of Minnesota / Masonic Cancer Center
Status: Active
Name Not Available
Mayo Clinic
Status: Active
Contact: Judy C. Szemere Boughey
Phone: 507-538-7623

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Name Not Available

North Carolina

Wake Forest University Health Sciences
Status: Active
Name Not Available


OHSU Knight Cancer Institute
Status: Active
Contact: Jenna Bucher
Phone: 503-418-9736
Email: bucherj@ohsu.edu


University of Pennsylvania / Abramson Cancer Center
Status: Active
Contact: Lauren Bayne
Phone: 215-349-5398
Email: lauren.bayne@uphs.upenn.edu

Trial Objectives and Outline

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.

Trial Phase & Type

Trial Phase

Phase II

Trial Type


Lead Organization

Lead Organization
QuantumLeap Healthcare Collaborative

Trial IDs

Primary ID 097517
Secondary IDs NCI-2015-00014
Clinicaltrials.gov ID NCT01042379