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

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.

Study Type: Interventional

Study Design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Study Primary Completion Date: February 2014

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.

Intervention(s) in this Clinical Trial

• Drug: Figitumumab
  • 20 mg/kg IV every 3 weeks during the 12 weekly treatment cycles post-randomization
• Drug: Neratinib
  • 240 mg po every week during the 12 weekly treatment cycles post-randomization
• Drug: ABT-888
  • ABT-888: 50 mg po bid during the 12 weekly treatment cycles post-randomization Carboplatin: AUC 6 IV every three weeks for four weeks during the 12 weekly treatment cycles post-randomization
• 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
• Drug: AMG 386
  • 15 mg/kg IV every week during 12 weekly treatment cycles post-randomization
• Drug: Conatumumab
  • 10 mg/kg IV every other week during 12 weekly treatment cycles post-randomization

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Figitumumab
  • Novel investigational agent
• Experimental: Neratinib
  • Novel investigational agent
• Experimental: ABT-888
  • Novel investigational agent
• Active Comparator: Standard Therapy
  • Paclitaxel, Herceptin followed by Doxorubicin and Cyclophosphamide treatment depending on HR/HER-2 status.
• Experimental: AMG 386
  • Novel investigational agent
• Experimental: Conatumumab
  • Novel investigational agent

Primary 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
    Safety Issue?: No

Secondary 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
    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
    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
    Safety Issue?: Yes
• MRV
  • Time Frame: Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery
    Safety Issue?: 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

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Foundation for the National Institutes of Health

Overall Clinical Trial Officials and Contacts

Laura Esserman, MD, MBA Principal Investigator University of California, San Francisco (UCSF)  

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

Information obtained from ClinicalTrials.gov on September 01, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01042379

Study ID Number: 097517

ClinicalTrials.gov Identifier: NCT01042379

Health Authority: United States: Food and Drug Administration

I-SPY 2 TRIAL Website