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
Fallopian Tube Neoplasms
Drug: Birinapant (TL32711)
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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|
- Clinical benefit defined as objective response (CR or PR defined by RECIST version 1.1 criteria) or disease stabilization for greater than 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Overall survival, safety and tolerability of single agent birinapant [ Time Frame: end of treatment ] [ Designated as safety issue: Yes ]
- Correlation of a gene index score based on the ratio of cFLIPl/cFLIPs and RIPK1 (and others candidate genes) with response to single agent birinapant [ Time Frame: end of treatment ] [ Designated as safety issue: No ]
- Relationship of serum and tumor levels of TNF alpha and TRAIL pre- and post- treatment with single agent birinapant [ Time Frame: end of treatment ] [ Designated as safety issue: No ]
- Pharmacodynamic changes in levels of the apoptosis/NFB pathway proteins cIAP1, cIAP2, cleaved PARP, cFLIP, RIPK1, activated caspase-8 and cleaved caspase 3 in paired pre and post-treatment tumor specimens and PBMCs [ Time Frame: end of treatment ] [ Designated as safety issue: No ]
- Correlation of clinical outcome with changes in the quantity of pre and post-treatment levels of cIAP1, cIAP2, PARP, c-FLIP, RIP1K, cleaved caspase-3 and and activated caspase-8 [ Time Frame: end of treatment ] [ Designated as safety issue: No ]
- Assessment of T-cell deficiency as a consequence of T-cell apoptosis induced by birinapant [ Time Frame: end of treatment ] [ Designated as safety issue: No ]
- Pharmacokinetics of birinapant in plasma and tumor tissues (if sufficient material) and to establish PK/PD correlations between drug exposure and efficacy/safety [ Time Frame: end of treatment ] [ Designated as safety issue: Yes ]
|Study Start Date:||August 2012|
|Study Completion Date:||April 2014|
|Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Drug: Birinapant (TL32711)
47mg/m2 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)|