This phase I/II trial studies how well birinapant and carboplatin work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back. Drugs used in chemotherapy, such as birinapant and carboplatin work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
PRIMARY OBJECTIVES: I. To assess whether addition of birinapant to carboplatin therapy can reduce the percentage of platinum resistant tumor initiating cells by 50% compared to pre-therapy biopsies in participants with recurrent high grade serous ovarian carcinomas (HGSOC) whose tumors score positive in the in vitro organoid bioassay test. II. Assess target engagement by comparing levels of cellular inhibitor of apoptosis protein (cIAP) and percentage of apoptotic cells in pre-versus post therapy tumor biopsies (obtained after three cycles of treatment). SECONDARY OBJECTIVES: I. To see if there is an increase in progression free survival of participants treated with co-therapy (birinapant/carboplatin) compared with historic controls. TERTIARY OBJECTIVES: I. Develop a companion diagnostic test by correlating clinical response seen in participants with two biomarker assays developed in our laboratory. 1. Measuring levels of cIAP protein by western blot in tumor biopsies obtained from participants prior to start of therapy. 2. Measuring percentage of cIAP positive cells by immunohistochemistry in tumor biopsies obtained from participants prior to start of therapy. OUTLINE: Patients receive birinapant intravenously (IV) over 30 minutes on days 1 and 8, and carboplatin IV over 30 minutes to 1 hour on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 2 years from Course 1, Day 1.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
Change in percentage of cancer initiating cells
Will be measured using a 3-dimensional organoid assay; population analysis using flow cytometry to measure the overall percentage of platinum resistant tumor initiating cells and by immunohistochemistry. Percent cellular inhibitor of apoptosis (cIAP) positive and amount of cIAP protein will be computed using either the non parametric Wilcoxon signed rank test or the paired t test if the data follow a normal distribution. Full summary statistics including the mean and median difference and the corresponding 95% confidence bounds will be reported. We will report scatter plots and the non parametric Spearman correlation coefficients among these four measures of platinum resistant tumor initiating cells pre-therapy as well as the post- minus pre-treatment difference.
Time frame: Baseline up to 2 years
Pharmacodynamic analysis of cellular inhibitor of apoptosis (cIAP) protein
Will measure the level of cIAP protein in pre- versus (vs). post-therapy tumors, measured by quantitative western blot, compared to a purified cIAP standard of known amount loaded on the same gel. Percent cIAP positive and amount of cIAP protein will be computed using either the non parametric Wilcoxon signed rank test or the paired t test if the data follow a normal distribution. Full summary statistics including the mean and median difference and the corresponding 95% confidence bounds will be reported. We will report scatter plots and the non parametric Spearman correlation coefficients among these four measures of platinum resistant tumor initiating cells pre-therapy as well as the post- minus pre-treatment difference.
Time frame: Baseline up to 2 years
Progression free survival (PFS) assessed using imaging (multiparametric magnetic resonance imaging [MRI] (primary modality of imaging) of computed tomography (CT) and the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
The secondary analysis in each group will be comparison of PFS to known historical PFS. The PFS curve will be estimated using the Kaplan-Meier method and the sample PFS curve will be compared to the known historical population curve using the one sample log rank test.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Correlative studies
Time frame: Start of therapy and progression of disease or death whichever comes first, assessed up to 2 years