Birinapant for Advanced Ovarian, Fallopian Tube, and Peritoneal Cancer
- Birinapant is an experimental cancer treatment drug. It removes certain proteins in cells, which helps to kill the cells. The drug is more likely to cause the death of cancer cells than normal cells because cancer cells have more of these proteins. Studies suggest that it can help treat ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. Researchers want to see how well Birinapant works against the three types of cancer.
- To test the effectiveness of Birinapant for ovarian, primary peritoneal, or fallopian tube cancer.
- Women at least 18 years of age who have ovarian, primary peritoneal, or fallopian tube cancer that has not responded to standard treatment.
- Participants will be screened with a physical exam and medical history. Blood and urine samples will also be collected. Tumor tissue samples may be collected before treatment. Imaging studies will also be performed.
- Participants will have an infusion of Birinapant once per week for 3 weeks in a row, followed by a break for a week on the fourth week. This 4-week schedule is one cycle of treatment.
- Treatment will be monitored with frequent blood tests and imaging studies.
- Another optional tumor biopsy will be collected 6 weeks after the start of treatment.
- Treatment will continue as long as the cancer does not grow and the side effects are not severe.
|Epithelial Ovarian Cancer Peritoneal Neoplasms Fallopian Tube Neoplasms||Drug: Birinapant (TL32711)||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase II Open Label Non-Randomized Single Agent Study of the SMAC (Second Mitochondrial-Derived Activator of Caspases)-Mimetic Birinapant (TL32711; NSC 756502) in Relapsed Platinum Resistant or Refractory Epithelial Ovarian Cancer, Primary Peritoneal|
- Objective Response (Complete Response (CR) or Partial Response (PR) Defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Criteria) or Disease Stabilization for Greater Than 6 Months [ Time Frame: 6 months ]Per the RECIST criteria, CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
- Number of Participants With Adverse Events [ Time Frame: 8 months ]Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
- Mean Plasma Concentration-Time Curve of Birinapant [ Time Frame: 30, 60, 120, 180 minutes after administration of first dose of Birinapant ]Measurement of the plasma concentration of the Birinapant over time. It is used to characterize drug absorption. The single values were analyzed with liquid chromatography/tandem mass spectrometry via a proprietary methodology (TetraLogic Pharma,Malvern, Pa). The values were grouped and averaged for each of the patients to obtain the mean value for each time point.
- Birinapant Concentration in Tumor Tissue [ Time Frame: Prior to treatment and 12 to 22 hours following Cycle 2 Day 15 ]Levels of Birinapant were measured in core needle biopsies of tumor that had been frozen at the time of acquisition.
- Calculated Volume of Distribution of Birinapant at Steady State (Vss) in Tumor Tissue [ Time Frame: 0-24hr ]Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
- Calculated Volume of Distribution of Birinapant at Steady State (Vss) in Plasma [ Time Frame: 0-24hr ]Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
- Ratio of Phosphorylated NF-kappaB-p65 Protein to Total NF-kappaBp65 Protein in Tumor Biopsy Samples [ Time Frame: 0-6 weeks ]Proteins were measured using capillary western blot and ratio was calculated between phosphorylated and total NF-kappaB p65. Core 1 tumor samples and peripheral blood mononuclear cells (PBMCs) from each time point were lysed in T-PER buffer (Thermo Scientific) for protein quantification by an automated capillary electrophoresis immunoassay system (Simple Western). The tumor protein lysate (40-60 ng) or PBMC protein lysate (16-77 ng) was analyzed according to the manufacturer's instructions (ProteinSimple, Santa Clara, Calif).
- Coexpression of Cleaved Caspase 3 and Gamma-H2AX in Fixed Specimens [ Time Frame: Pre treatment and post treatment of Birinapant, approximately 0-6 weeks ]Tumor biopsies were measured for cleaved caspase 3 and gamma-H2A.X by immunofluorescence microscopy. Fold change was calculated by comparing the post-treatment measurements to the pre-treatment levels.
- Total Clearance of Birinapant After Administration [ Time Frame: 0-24hr ]Clearance is a quantitative measure of the rate at which a drug substance is removed from the body.
|Actual Study Start Date:||August 15, 2012|
|Study Completion Date:||April 30, 2014|
|Primary Completion Date:||December 9, 2013 (Final data collection date for primary outcome measure)|
Experimental: Birinapant for Advanced Ovarian,Fallopian Tube & Peritoneal Ca
Drug: Birinapant (TL32711)
47mg/m^2 intravenous (IV) on days 1, 8 and 15 of each 28 day cycle
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01681368
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Christina M Annunziata, M.D.||National Cancer Institute (NCI)|