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

Overview[ - collapse ][ - ]

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.
ConditionBreast Neoplasms
Breast Cancer
Breast Tumors
InterventionDrug: Standard Therapy
Drug: AMG 386
Drug: AMG 479 (Ganitumab) plus Metformin
Drug: MK-2206 with or without Trastuzumab
Drug: AMG 386 and Trastuzumab
Drug: T-DM1 and Pertuzumab
Drug: Pertuzumab and Trastuzumab
PhasePhase 2
SponsorQuantumLeap Healthcare Collaborative
Responsible PartyQuantumLeap Healthcare Collaborative
ClinicalTrials.gov IdentifierNCT01042379
First ReceivedDecember 31, 2009
Last UpdatedFebruary 20, 2014
Last verifiedFebruary 2014

Tracking Information[ + expand ][ + ]

First Received DateDecember 31, 2009
Last Updated DateFebruary 20, 2014
Start DateMarch 2010
Estimated Primary Completion DateNovember 2014
Current Primary Outcome MeasuresDetermine 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]
Current 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]

Descriptive Information[ + expand ][ + ]

Brief TitleI-SPY 2 TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer
Official TitleI-SPY 2 Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)
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-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.
Study TypeInterventional
Study PhasePhase 2
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Breast Neoplasms
  • Breast Cancer
  • Breast Tumors
InterventionDrug: 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: 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 Names:
GanitumabDrug: MK-2206 with or without Trastuzumab
MK-2206: 135 mg every week during 12 weekly treatment cycles post-randomization; Trastuzumab: 4 mg/kg (loading dose) week 1 and 2 mg/kg weekly (weeks 2-12) post-randomization
Drug: AMG 386 and Trastuzumab
AMG 386: 15 mg/kg IV every week during 12 weekly treatment cycles post-randomization; Trastuzumab: 4 mg/kg (loading dose) week 1 and 2 mg/kg weekly (weeks 2-12) post-randomization
Drug: T-DM1 and Pertuzumab
T-DM1: 3.6 mg/kg IV every 2 weeks (weeks 1, 4, 7, 10) post-randomization; Pertuzumab: 840 mg IV (loading dose) week 1 and 420 mg every 3 weeks (weeks 4, 7, 10) post-randomization
Drug: Pertuzumab and Trastuzumab
Pertuzumab: 840 mg IV (loading dose) week 1 and 420 mg every 3 weeks (weeks 4, 7, 10) post-randomization; Trastuzumab: 4 mg/kg (loading dose) week 1 and 2 mg/kg weekly (weeks 2-12) post-randomization
Study Arm (s)
  • 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: AMG 479 (Ganitumab) plus Metformin
    Novel investigational agent
  • Experimental: MK-2206 with or without Trastuzumab
    Novel investigational agent
  • Experimental: AMG 386 and Trastuzumab
    Novel Investigational Agent
  • Experimental: T-DM1 and Pertuzumab
    Novel Investigational Agent
  • Experimental: Pertuzumab and Trastuzumab
    Novel Investigational Agent

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment800
Estimated Completion DateNovember 2014
Estimated Primary Completion DateFebruary 2014
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
GenderFemale
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Meredith Buxton, MPhil, MPH
415-353-7357
meredith.buxton@ucsfmedctr.org
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01042379
Other Study ID Numbers097517
Has Data Monitoring CommitteeYes
Information Provided ByQuantumLeap Healthcare Collaborative
Study SponsorQuantumLeap Healthcare Collaborative
CollaboratorsNot Provided
Investigators Principal Investigator: Laura Esserman, MD, MBA University of California, San Francisco (UCSF)
Verification DateFebruary 2014

Locations[ + expand ][ + ]

University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
Contact: Valerie Caterinicchia, RN, BSN | 205-934-5367 | val7@uab.edu
Principal Investigator: Andres Forero, MD
Recruiting
Mayo Clinic - Scottsdale
Scottsdale, Arizona, United States, 85259
Active, not recruiting
University of Arizona
Tucson, Arizona, United States, 85724
Contact: Amy S Bauland | 520-694-0859 | abauland@azcc.arizona.edu
Principal Investigator: Rebecca Viscusi, MD
Recruiting
University of California San Diego
La Jolla, California, United States, 92093-0698
Contact: Cynthia Meyer | 858-822-6575 | cjmeyer@ucsd.edu
Principal Investigator: Anne Wallace, MD
Recruiting
University of Southern California
Los Angeles, California, United States, 90033
Contact: Debu Tripathy, MD | 323-865-3900 | Tripathy@usc.edu
Principal Investigator: Debasish Tripathy, MD
Recruiting
University of California San Francisco (UCSF)
San Francisco, California, United States, 94115
| 877-827-3222
Principal Investigator: Amy Jo Chien, MD
Recruiting
University of Colorado
Aurora, Colorado, United States, 80045
Contact: Tessa Mcspadden | 720-848-0609 | tessa.mcspadden@ucdenver.edu
Principal Investigator: Anthony Elias, MD
Recruiting
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
Contact: Minetta Liu, MD | 202-444-3677 | Liumc@georgetown.edu
Principal Investigator: Claudine Isaacs, MD
Recruiting
Emory University
Atlanta, Georgia, United States, 30322
Active, not recruiting
University of Chicago
Chicago, Illinois, United States, 60453
Contact: Jean Gibson | 773-834-2167 | jgibson@medicine.bsd.uchicago.edu
Principal Investigator: Rita Nanda, MD
Recruiting
Loyola University
Maywood, Illinois, United States, 60153
Contact: Kathy Czaplicki | 708-327-3322 | kczapli@lumc.edu
Principal Investigator: Kathy Albain, MD
Recruiting
University of Kansas
Westwood, Kansas, United States, 66205
Active, not recruiting
University of Minnesota
Minneapolis, Minnesota, United States, 55455
Contact: Charlotte Smith | 612-625-9498 | Smit4652@umn.edu
Principal Investigator: Doug Yee, MD
Recruiting
Mayo Clinic
Rochester, Minnesota, United States, 55905
| 507-538-7623
Principal Investigator: Judy C Boughey, MD
Recruiting
Oregon Health & Science Institute (OHSU)
Portland, Oregon, United States, 97239
Contact: Deirdre Nauman, BSN,CCRP | 503-494-3078 | naumand@ohsu.edu
Principal Investigator: Stephen Y Chui, MD
Recruiting
University of Pennsylvania (U Penn)
Philadelphia, Pennsylvania, United States, 19104
Contact: Luke Velders | 215-615-6821 | Luke.Velders@uphs.upenn.edu
Principal Investigator: Angela DeMichele, MD
Recruiting
University of Texas, Southwestern Medical Center
Dallas, Texas, United States, 75390-9155
Contact: Barabara Staves, BS | 214-648-1988 | barbara.staves@utsouthwestern.edu
Principal Investigator: David Euhus, MD
Recruiting
University of Texas, M.D. Anderson Cancer Center
Houston, Texas, United States, 77230-1439
Contact: Cara Dunlap, RN | 713-745-8748 | CLDunlap@mdanderson.org
Principal Investigator: Stacy Moulder, MD, MSCI
Recruiting
Inova Health System
Falls Church, Virginia, United States, 22042
Contact: Alyssa Bruflodt | 703-776-3565 | Alyssa.Bruflodt@inova.org
Principal Investigator: Kirsten Edmiston, MD, FACS
Recruiting
Swedish Cancer Institute
Seattle, Washington, United States, 98104
Contact: Barry Boatman, RN | 206-215-3086 | CancerResearch@swedish.org
Principal Investigator: Hank Kaplan, MD
Recruiting
University of Washington
Seattle, Washington, United States, 98115
Principal Investigator: Larissa Korde, MD, MPH
Recruiting