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

Sponsor:	Foundation for the National Institutes of Health
Information provided by (Responsible Party):	Foundation for the National Institutes of Health
ClinicalTrials.gov Identifier:	NCT01042379

Purpose

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: Neratinib Drug: ABT-888 Drug: Standard Therapy Drug: AMG 386 Drug: AMG 479 (Ganitumab) plus Metformin	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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Metformin Metformin hydrochloride

U.S. FDA Resources

Further study details as provided by Foundation for the National Institutes of Health:

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
Experimental: Neratinib Novel investigational agent	Drug: Neratinib 240 mg po every week during the 12 weekly treatment cycles post-randomization
Experimental: ABT-888 Novel investigational agent	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
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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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

Contacts

Contact: Meredith Buxton, MPhil, MPH	415-353-7357	meredith.buxton@ucsfmedctr.org
Contact: Donya Bagheri, MS, DABT	650-691-4400 ext 116	dbagheri@ccsainc.com

Locations

United States, Alabama
University of Alabama at Birmingham	Not yet recruiting
Birmingham, Alabama, United States, 35294
Principal Investigator: Andres Forero, MD
United States, Arizona
Mayo Clinic - Scottsdale	Recruiting
Scottsdale, Arizona, United States, 85259
Contact 507-538-7623
Principal Investigator: Donald Northfelt, MD
University of Arizona	Recruiting
Tucson, Arizona, United States, 85724
Contact: Amy S Bauland 520-694-0859 abauland@azcc.arizona.edu
Principal Investigator: Julie Lang, 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: Caroline Jamison 720-848-3428 Caroline.Jamison@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: Minetta Liu, MD
United States, Georgia
Emory University	Recruiting
Atlanta, Georgia, United States, 30322
Contact: Latisha Pace 404-778-1559 lrpace@emory.edu
Principal Investigator: William C Wood, MD
United States, Illinois
University of Chicago	Recruiting
Chicago, Illinois, United States, 60453
Contact 773-834-7424
Principal Investigator: Olufunmilayo Olopade, 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	Recruiting
Westwood, Kansas, United States, 66205
Contact: Cinda Lyon, RN 913-588-2567 clyon@kumc.edu
Principal Investigator: Qamar Khan, MD
United States, Minnesota
University of Minnesota	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Charlotte Smith 612-625-9498 Smit4652@umn.edu
Principal Investigator: Tufia Haddad, 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, OCN 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: Lajos Pusztai, MD 713-792-2817
Principal Investigator: Lajos Pusztai, MD
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: Yolanda Seegmiller 206-215-5962 Yolonda.Seegmiller@Swedish.org
Contact: Heather Sloan 206-386-3650 Heather.Sloan@Swedish.org
Principal Investigator: Hank Kaplan, MD
University of Washington	Not yet recruiting
Seattle, Washington, United States, 98115
Principal Investigator: Larissa Korde, MD, MPH

Sponsors and Collaborators

Foundation for the National Institutes of Health

Investigators

Principal Investigator:

Laura Esserman, MD, MBA

University of California, San Francisco (UCSF)

More Information

Additional Information:

I-SPY 2 TRIAL Website This link exits the ClinicalTrials.gov site

Publications:

Barker AD, Sigman CC, Kelloff GJ, Hylton NM, Berry DA, Esserman LJ. I-SPY 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy. Clin Pharmacol Ther. 2009 Jul;86(1):97-100. Epub 2009 May 13.

Responsible Party:	Foundation for the National Institutes of Health
ClinicalTrials.gov Identifier:	NCT01042379 History of Changes
Other Study ID Numbers:	097517
Study First Received:	December 31, 2009
Last Updated:	December 21, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Foundation for the National Institutes of Health:

I-SPY 2
Neoadjuvant
Breast
Cancer
Neoplasm
Adaptive

pCR
Pathologic Complete Response
MRV
Biomarkers signature
MRI

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases

Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2012