Clinical trial NCT01042379: I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer
Official title: I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Neoplasms
Breast Cancer
Breast Tumors
Angiosarcoma
TNBC - Triple-Negative Breast Cancer
HER2-positive Breast Cancer
HER2-negative Breast Cancer
Hormone Receptor Positive Tumor
Hormone Receptor Negative Tumor
Early-stage Breast Cancer
Locally Advanced Breast Cancer
Keywords: Neoadjuvant
Breast
Cancer
Neoplasm
Adaptive
pCR
Pathologic Complete Response
Biomarkers signature
MRI Volume
Endocrine Therapy
Chemotherapy
Immunotherapy
Lead sponsor: QuantumLeap Healthcare Collaborative
Sponsor class: OTHER
First posted: 2010-01-05
Enrollment: 5000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: I-SPY2 will assess the efficacy of novel drugs in sequence with standard chemotherapy. The goal is identify treatment strategies for subsets on the basis of molecular characteristics (biomarker signatures) of their disease with high estimated pCR rate. As described for previous adaptive trials, novel regimens with sufficiently high activities alone and contribute to treatment strategies that show a high Bayesian predictive probability of being more effective than the dynamic control will graduate from the trial with their corresponding biomarker signature(s). Treatment strategies 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.

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

Primary outcomes:
measure: 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.
timeFrame: Post surgery based on upto 36-week treatment
Secondary outcomes:
measure: Establishing predictive and prognostic indices based on qualification and exploratory markers to predict pCR and residual cancer burden (RCB).
timeFrame: Blood and Tissue Collection: Baseline, Post-Randomization, Pre-AC, Pre- and Post-Surgery
measure: To determine three- and five-year relapse-free survival (RFS) and OS among the treatment arms.
timeFrame: Three- and Five-Year Post-surgery Follow-up
measure: To determine incidence of adverse events (AEs), serious adverse events (SAEs), and laboratory abnormalities of each investigational agent tested.
timeFrame: Post-Randomization, Pre-AC, Pre-Surgery, Post-Surgery upto One Year during follow-up
measure: MRI Volume
timeFrame: Four time points during the on-study phase: Baseline, Post-randomization, Pre-AC treatment and Pre-Surgery
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic - Scottsdale
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Newport Beach
country: United States
facility: HOAG Memorial Hospital Presbyterian
state: California
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF)
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Loyola University
state: Illinois
city: Westwood
country: United States
facility: University of Kansas
state: Kansas
city: Lansing
country: United States
facility: Herbert-Herman Cancer Center, Sparrow Hospital
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center / NYU Langone Health
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Wilmot Cancer Institute
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Comprehensive Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science Institute (OHSU)
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania (U Penn)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University Pittsburgh Medical Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Clinical Research
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas, Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas, M.D. Anderson Cancer Center
state: Texas
city: Falls Church
country: United States
facility: Inova Health System
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of California, San Francisco
name: Laura Esserman, MD, MBA
role: PRINCIPAL_INVESTIGATOR
References:
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