Abraxane With or Without Tigatuzumab in Patients With Metastatic, Triple Negative Breast Cancer
Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer deaths in American women. Metastatic disease including metastatic breast cancer unfortunately remains incurable. One reason is due to the inability to develop specific therapies for specific cancer subsets.
The use of modern genomic techniques has significantly enhanced our recent understanding of breast cancer biology. Five distinct breast cancer subsets have been recognized, one of which is basal-like breast cancer. Basal-like breast cancer is typically estrogen receptor (ER) negative, progesterone receptor (PR) negative and human epidermal growth factor receptor 2 (HER-2-Neu) negative. This is referred to as triple negative breast cancer or TBNC. TBNC represents a significant proportion of breast cancer patients (10-20%) and has a poor prognosis with no targeted approach to therapy as of yet.
Tigatuzumab is a humanized monoclonal antibody targeting a death receptor on the breast cancer cells. Previous studies have shown that combining antibodies with selected chemotherapy agents have induced tumor cell death. The hypothesis of this study is to use tigatuzumab and combine it with Abraxane to serve as a targeting agent in metastatic TBNC patients.
|Breast Cancer Triple Negative Breast Cancer Stage IV Breast Cancer Metastatic Breast Cancer||Drug: Abraxane alone Drug: Abraxane + Tigatuzumab||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||An Open Label, Randomized, Phase II Trial of Abraxane (Paclitaxel Albumin-Bound Particles for Injectable Suspension), With or Without Tigatuzumab (a Humanized Monoclonal Antibody Targeting Death Receptor 5) in Patients With Metastatic, Triple Negative (ER, PR, and HER-2 Negative) Breast Cancer|
- Objective Response Rate [ Time Frame: Baseline to 6 months ]Patient response rates will be measured by the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI. Responses include the following: Complete Response (CR) disappearance of all target lesions; Partial Response (PR) at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) best response from the start of treatment until disease progression.
- Number of Participants With Serious Adverse Events [ Time Frame: Baseline to 6 months ]Patients will be assessed throughout the study for Grade 4 or 5 toxicities utilizing the Common Toxicity Criteria for Adverse Events (CTCAE) v4.0.
- Progression-free Survival [ Time Frame: Baseline through 24 months ]Progression is defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
|Study Start Date:||March 2011|
|Study Completion Date:||June 2017|
|Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Experimental: Abraxane + Tigatuzumab
Patients will receive Abraxane at 100 mg/m2 X 3 doses on Days 1, 8, and 15 at 28-day intervals and tigatuzumab to be administered as a 10 mg/kg loading dose followed by 5 mg/kg for the first cycle and then every other week on Days 1 and 15 for subsequent cycles. Patients will be evaluated for response every 8 weeks. Patients with disease progression will be taken off the study.
Drug: Abraxane + Tigatuzumab
Tigatuzumab will be administered as a loading dose of 10 mg/kg on Day 1, then 5 mg/kg on Day 15 and then every other week on Days 1 and 15 of subsequent cycles. It will be given as an IV infusion over 60 minutes or less. No dose reductions will be allowed. Tigatuzumab will be administered in combination with the Abraxane according to the intervention described for it.
Other Name: Tigatuzumab, CS-1008
Experimental: Abraxane alone
Patients will receive Abraxane at 100 mg/m2 weekly X 3 doses on Days 1, 8, and 15 at 28-day intervals. Patients will have the option to crossover to the combination arm based upon the pre-clinical data.
Drug: Abraxane alone
100 mg/m2 weekly X 3 doses (Days 1, 8, 15) at 28-day intervals until disease progression or unacceptable toxicity. Abraxane will be administered on an outpatient basis by an IV infusion over 30 minutes. Patients will be evaluated for response every 2 cycles (every 8 weeks).
Other Name: Abraxane, also ABI-007
Please refer to this study by its ClinicalTrials.gov identifier: NCT01307891
|United States, Alabama|
|University of Alabama at Birmingham (UAB)|
|Birmingham, Alabama, United States, 35294|
|United States, District of Columbia|
|Georgetown University Medical Center|
|Washington, D.C., District of Columbia, United States, 20007|
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|United States, Indiana|
|Indiana University Melvin and Bren Simon Cancer Center|
|Indianapolis, Indiana, United States, 46202|
|United States, Massachusetts|
|Dana Farber Cancer Center Institute|
|Boston, Massachusetts, United States, 02215|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, North Carolina|
|University of North Carolina|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37232|
|United States, Texas|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Andres Forero, M.D.||University of Alabama at Birmingham|