This pilot early phase I trial studies talazoparib to determine if certain characteristics of the deoxyribonucleic acid (DNA) affect how the disease responds to therapy in patients with ovarian, fallopian tube, or primary peritoneal cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment (advanced). Studying samples of tissue in the laboratory from patients receiving talazoparib may help doctors learn more about the effects of talazoparib on cells and may help doctors understand how well patients respond to treatment.
PRIMARY OBJECTIVES: I. To explore basal levels and effects of talazoparib (BMN 673) on DNA copy number, loss of heterozygosity and mutation, and level of ribonucleic acid (RNA) and protein expression (together described as "molecular results") in homologous recombination-related pathways before and after treatment in women with primary advanced high grade serous ovarian, fallopian tube, or primary peritoneal cancer. SECONDARY OBJECTIVES: I. To correlate molecular results to clinical endpoints including response and survival. II. To correlate molecular results to pathologic endpoints including tumor volume and apoptosis. III. To compare DNA copy number and level of RNA and protein expression in homologous recombination-related pathways in tissue from patients treated with BMN 673 to those untreated with BMN 673 in the preoperative period. IV. To determine the toxicity of daily BMN 673 given preoperatively, with a focus on postoperative wound healing. V. To determine feasibility of daily BMN 673 given preoperatively. OUTLINE: Patients receive talazoparib orally (PO) once daily (QD) for up to 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
4
Correlative studies
BMN673 given at a dose of 1 mg orally once daily. Participants begin taking BMN 673 tablets by mouth every day, starting on the day of scheduled laparoscopy. Participants take the study drug for at least 7 days before scheduled tumor reduction surgery.
M D Anderson Cancer Center
Houston, Texas, United States
The Woman's Hospital of Texas
Houston, Texas, United States
MD Anderson Regional Care Center-Katy
Houston, Texas, United States
MD Anderson Regional Care Center-Bay Area
Nassau Bay, Texas, United States
MD Anderson Regional Care Center-Sugar Land
Sugar Land, Texas, United States
MD Anderson Regional Care Center-The Woodlands
The Woodlands, Texas, United States
Change in deoxyribonucleic acid (DNA) copy number
Will use descriptive statistics and graphical methods to summarize the change in DNA copy number. Will summarize these changes for untreated patients. Will use a paired t-test to test that mean changes are different from 0. Will test median changes with a Wilcoxon signed-rank test. Will use a 2-sample t-test to compare mean changes between treated and untreated patients. Will compare median changes between treated and untreated patients with a Wilcoxon rank sum test.
Time frame: Baseline to the day of tumor reductive surgery
Change in ribonucleic acid (RNA) protein expression
Will use descriptive statistics and graphical methods to summarize the change in RNA protein expression. Will summarize these changes for untreated patients. Will use a paired t-test to test that mean changes are different from 0. Will test median changes with a Wilcoxon signed-rank test. Will use a 2-sample t-test to compare mean changes between treated and untreated patients. Will compare median changes between treated and untreated patients with a Wilcoxon rank sum test. Will use McNemar's test to compare the changes based on homologous recombination deficiency (HRD) assay results.
Time frame: Baseline to the day of tumor reductive surgery
Overall survival
Will use Cox proportional hazards regression methods to model overall survival as a function of DNA copy number, changes in RNA protein expression, and HRD assay result.
Time frame: Up to 3 years
Tumor response
Will use logistic regression methods to model tumor response as a function of changes in DNA copy number, changes in RNA protein expression, and HRD assay result.
Time frame: Up to 30 days
Tumor volume
Will use linear regression methods to model tumor volume as a function of changes in DNA copy number, changes in RNA protein expression, and HRD assay result.
Time frame: Up to 30 days
Apoptosis
Will use linear regression methods to model apoptosis as a function of changes in DNA copy number, changes in RNA protein expression, and HRD assay result.
Time frame: Up to 30 days
Completion Rate of BMN 673 to determine feasibility
Treatment with BMN 673 considered feasible if 70% of patients complete all planned doses of talazoparib and post-operative chemotherapy.
Time frame: Up to 30 days
Incidence of adverse events
Will tabulate toxicities by grade and relationship to treatment.
Time frame: Up to 30 days
Proportion of patients that exhibit an increase (or decrease) in RNA protein expression greater than 50%
Will use Fisher's exact test to compare treated and untreated patients with respect to the proportion of patients that exhibit an increase (or decrease) in RNA protein expression. Will compare the mean change in RNA protein expression between those patients with and without a HRD on assay at baseline using a 2-sample t-test. Will compare the median changes between these 2 groups of patients with a Wilcoxon rank sum test. Will compare these 2 groups of patients with respect to HRD assay result using Fisher's exact test.
Time frame: Baseline to the day of tumor reductive surgery
Change in DNA copy number
Will use Fisher's exact test to compare treated and untreated patients with respect to the increase (or decrease) in DNA copy number. Will compare the mean change in DNA copy number between those patients with and without a HRD on assay at baseline using a 2-sample t-test. Will compare the median changes between these 2 groups of patients with a Wilcoxon rank sum test. Will compare these 2 groups of patients with respect to HRD assay result using Fisher's exact test.
Time frame: Baseline to the day of tumor reductive surgery
Change in RNA protein expression
Will use Fisher's exact test to compare treated and untreated patients with respect to the increase (or decrease) in RNA protein expression. Will compare the mean change in RNA protein expression between those patients with and without a HRD on assay at baseline using a 2-sample t-test. Will compare the median changes between these 2 groups of patients with a Wilcoxon rank sum test. Will compare these 2 groups of patients with respect to HRD assay result using Fisher's exact test.
Time frame: Baseline to the day of tumor reductive surgery
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