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. |
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Condition | Breast Neoplasms Breast Cancer Breast Tumors |
Intervention | 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 | Phase 2 |
Sponsor | QuantumLeap Healthcare Collaborative |
Responsible Party | QuantumLeap Healthcare Collaborative |
ClinicalTrials.gov Identifier | NCT01042379 |
First Received | December 31, 2009 |
Last Updated | February 20, 2014 |
Last verified | February 2014 |
Tracking Information[ + expand ][ + ]
First Received Date | December 31, 2009 |
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Last Updated Date | February 20, 2014 |
Start Date | March 2010 |
Estimated Primary Completion Date | November 2014 |
Current 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] |
Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
Brief Title | I-SPY 2 TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer |
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Official Title | I-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 Type | Interventional |
Study Phase | Phase 2 |
Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment |
Condition |
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Intervention | 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: 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) |
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Recruitment Information[ + expand ][ + ]
Recruitment Status | Recruiting |
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Estimated Enrollment | 800 |
Estimated Completion Date | November 2014 |
Estimated Primary Completion Date | February 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 |
Gender | Female |
Ages | 18 Years |
Accepts Healthy Volunteers | No |
Contacts | Contact: Meredith Buxton, MPhil, MPH 415-353-7357 meredith.buxton@ucsfmedctr.org |
Location Countries | United States |
Administrative Information[ + expand ][ + ]
NCT Number | NCT01042379 |
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Other Study ID Numbers | 097517 |
Has Data Monitoring Committee | Yes |
Information Provided By | QuantumLeap Healthcare Collaborative |
Study Sponsor | QuantumLeap Healthcare Collaborative |
Collaborators | Not Provided |
Investigators | Principal Investigator: Laura Esserman, MD, MBA University of California, San Francisco (UCSF) |
Verification Date | February 2014 |
Locations[ + expand ][ + ]
University of Alabama at Birmingham | Birmingham, Alabama, United States, 35294 Contact: Valerie Caterinicchia, RN, BSN | 205-934-5367 | val7@uab.eduPrincipal Investigator: Andres Forero, MD Recruiting |
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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.eduPrincipal 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.eduPrincipal Investigator: Anne Wallace, MD Recruiting |
University of Southern California | Los Angeles, California, United States, 90033 Contact: Debu Tripathy, MD | 323-865-3900 | Tripathy@usc.eduPrincipal Investigator: Debasish Tripathy, MD Recruiting |
University of California San Francisco (UCSF) | San Francisco, California, United States, 94115 | 877-827-3222Principal Investigator: Amy Jo Chien, MD Recruiting |
University of Colorado | Aurora, Colorado, United States, 80045 Contact: Tessa Mcspadden | 720-848-0609 | tessa.mcspadden@ucdenver.eduPrincipal 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.eduPrincipal 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.eduPrincipal Investigator: Rita Nanda, MD Recruiting |
Loyola University | Maywood, Illinois, United States, 60153 Contact: Kathy Czaplicki | 708-327-3322 | kczapli@lumc.eduPrincipal 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.eduPrincipal Investigator: Doug Yee, MD Recruiting |
Mayo Clinic | Rochester, Minnesota, United States, 55905 | 507-538-7623Principal 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.eduPrincipal 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.eduPrincipal 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.eduPrincipal 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.orgPrincipal Investigator: Stacy Moulder, MD, MSCI Recruiting |
Inova Health System | Falls Church, Virginia, United States, 22042 Contact: Alyssa Bruflodt | 703-776-3565 | Alyssa.Bruflodt@inova.orgPrincipal Investigator: Kirsten Edmiston, MD, FACS Recruiting |
Swedish Cancer Institute | Seattle, Washington, United States, 98104 Contact: Barry Boatman, RN | 206-215-3086 | CancerResearch@swedish.orgPrincipal Investigator: Hank Kaplan, MD Recruiting |
University of Washington | Seattle, Washington, United States, 98115 Principal Investigator: Larissa Korde, MD, MPHRecruiting |