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.
Triple Negative Breast Cancer
Stage IV Breast Cancer
Metastatic Breast Cancer
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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: Interim analysis will be conducted after 11 patients have been accrued and completed in each arm. Final analysis will be at the conclusion of the study: about 2 years. ] [ Designated as safety issue: No ]The primary endpoint of this trial is the objective response rate as measured by complete responses and partial responses for the combination of tigatuzumab and Abraxane or Abraxane alone in patients with metastatic triple negative breast cancer. This information will be used to generate hypotheses for further trials.
- Characterization of the safety profile and treatment tolerance [ Time Frame: An interim safety analysis will be done for the first 6 patients enrolled in the combination group. The study will be on hold at that time. Final toxicity and safety evaluation will be at the conclusion of the study: about 2 years. ] [ Designated as safety issue: Yes ]The trial will allow for further characterization of the safety profile and treatment tolerance of tigatuzumab in combination with Abraxane.
- Determine progression free survival [ Time Frame: ~2 years ] [ Designated as safety issue: No ]The study will allow determination of progression free survival for both groups.
- Correlate the gene expression profile and the proliferation/apoptotic markers with disease responses observed from both groups of the study. [ Time Frame: ~2 years ] [ Designated as safety issue: No ]Correlate the pre-treatment tumor gene expression profile, DR5/DDX3/IAP profile, and proliferation/apoptotic with the objective response rate and progression free survival observed in both groups.
- Correlate circulating tumor cells with the objective response rate and the progression free survival observed in both groups. [ Time Frame: ~2 years ] [ Designated as safety issue: No ]Correlate serial measures of circulating tumor cells with the objective response rate and progression free survival observed in both groups. Changes will also be observed in apoptosis marker staining in the circulating tumor cells and correlation will be made to the corresponding serum levels.
- Characterize the immune response to tigatuzumab [ Time Frame: ~2 years ] [ Designated as safety issue: No ]Characterize patient immune response to tigatuzumab when administered in combination with Abraxane.
- Evaluate the pharmacokinetics of the combined drugs (UAB only) [ Time Frame: ~2 years ] [ Designated as safety issue: No ]Determine the pharmacokinetics of tigatuzumab and Abraxane when given in combination. (This will be done only at UAB.)
|Study Start Date:||March 2011|
|Estimated Study Completion Date:||May 2017|
|Estimated Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
Experimental: Combination Abraxane and Tigatuzumab
Patients will receive Abraxane at 100 mg/m2 X 3 doses on Days 1, 8, and 15 at 28-day intervals in combination with 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.
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. Treatment may continue without interruption in patients with complete response (CR), partial response (PR), or stable disease (SD) until there is progression of the disease or unacceptable toxicity. Patients will have the option to crossover to the combination arm based upon the pre-clinical data.
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
The study is an open-label randomized, multi-institutional, phase II clinical trial of Abraxane in combination with tigatuzumab or Abraxane as a single agent in patients with TNBC. Randomization (2:1) will be made from these two categories: TBNC patients with no prior chemotherapy for metastatic disease or TBNC patients with prior taxane (except Abraxane) therapy for metastatic disease. Patients randomized to Abraxane alone may be allowed to cross over to the combination of Abraxane + tigatuzumab if there is disease progression.
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, 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|