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

Study ID

Cancer Related

Healthy Volunteers

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • Zale Lipshy University Hospital
  • Parkland Health & Hospital System

J Susan Armstrong

Principal Investigator
Barbara Haley, M.D.

Official Title

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

Brief Overview

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.


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.

Participant 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

- 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

- 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,

- 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