I-SPY 2 TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer
This study is currently recruiting participants.
Verified March 2013 by Foundation for the National Institutes of Health
Sponsor:
Foundation for the National Institutes of Health
Information provided by (Responsible Party):
Foundation for the National Institutes of Health
ClinicalTrials.gov Identifier:
NCT01042379
First received: December 31, 2009
Last updated: March 14, 2013
Last verified: March 2013
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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 Drug: MK-2206 with or without Trastuzumab Drug: AMG 386 and Trastuzumab Drug: T-DM1 and Pertuzumab Drug: Pertuzumab and Trastuzumab |
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:
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 qd 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
|
|
Experimental: MK-2206 with or without Trastuzumab
Novel investigational agent
|
Drug: 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
|
|
Experimental: AMG 386 and Trastuzumab
Novel Investigational Agent
|
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
|
|
Experimental: T-DM1 and Pertuzumab
Novel Investigational Agent
|
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
|
|
Experimental: Pertuzumab and Trastuzumab
Novel Investigational Agent
|
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
|
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 | Recruiting |
| Birmingham, Alabama, United States, 35294 | |
| Contact: Valerie Caterinicchia, RN, BSN 205-934-5367 val7@uab.edu | |
| Principal Investigator: Andres Forero, MD | |
| United States, Arizona | |
| Mayo Clinic - Scottsdale | Active, not recruiting |
| Scottsdale, Arizona, United States, 85259 | |
| University of Arizona | Recruiting |
| Tucson, Arizona, United States, 85724 | |
| Contact: Amy S Bauland 520-694-0859 abauland@azcc.arizona.edu | |
| Principal Investigator: Rebecca Viscusi, 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: Tessa Mcspadden 720-848-0609 tessa.mcspadden@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: Claudine Isaacs, MD | |
| United States, Georgia | |
| Emory University | Active, not recruiting |
| Atlanta, Georgia, United States, 30322 | |
| United States, Illinois | |
| University of Chicago | Recruiting |
| Chicago, Illinois, United States, 60453 | |
| Contact: Jean Gibson 773-834-2167 jgibson@medicine.bsd.uchicago.edu | |
| Principal Investigator: Rita Nanda, 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 | Active, not recruiting |
| Westwood, Kansas, United States, 66205 | |
| United States, Minnesota | |
| University of Minnesota | Recruiting |
| Minneapolis, Minnesota, United States, 55455 | |
| Contact: Charlotte Smith 612-625-9498 Smit4652@umn.edu | |
| Principal Investigator: Doug Yee, 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 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: Cara Dunlap, RN 713-745-8748 CLDunlap@mdanderson.org | |
| Principal Investigator: Stacy Moulder, MD, MSCI | |
| 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: Barry Boatman, RN 206-215-3086 CancerResearch@swedish.org | |
| Principal Investigator: Hank Kaplan, MD | |
| Principal Investigator: Erin Ellis, MD | |
| University of Washington | 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:
Publications:
| 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: | March 14, 2013 |
| 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 |
Trastuzumab Hypoglycemic Agents Physiological Effects of Drugs Pharmacologic Actions Antineoplastic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 22, 2013