This early phase I trial studies how well olaparib works in treating patients with newly diagnosed BRCA-mutant ovarian, primary peritoneal, or fallopian cancer before surgery. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To determine the feasibility of daily olaparib given in the neoadjuvant setting in women with primary advanced high grade non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer. SECONDARY OBJECTIVES: I. Estimate efficacy of olaparib given in the neoadjuvant setting using response rate (by Response Evaluation Criteria in Solid Tumors \[RECIST\] in subjects with measurable disease). II. Estimate proportion of subjects able to proceed immediately to interval tumor reductive surgery (without chemotherapy). III. Determine progression-free survival (PFS). IV. Determine complete pathologic response rate at the time of surgery. V. Determine the toxicity of daily olaparib given in the neoadjuvant setting. VI. Evaluate the toxicity of chemotherapy given after neoadjuvant olaparib. VII. Measure longitudinal symptom burden of study subjects treated with neoadjuvant olaparib and chemotherapy after olaparib. EXPLORATORY OBJECTIVES: I. Explore deoxyribonucleic acid (DNA) copy number and level of ribonucleic acid (RNA) and protein expression in homologous recombination-related pathways before and after treatment with olaparib in women with primary advanced high grade non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer. II. Correlate molecular results to clinical endpoints including response and survival. OUTLINE: Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. After treatment, patients either undergo surgery then receive standard chemotherapy for up to 4 cycles or receive standard chemotherapy within 14 days for up to 4 cycles then undergo surgery in the absence of disease progression or unacceptable toxicity at the discretion of the treating physician. After completion of study treatment, patients are followed up at 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Given standard chemotherapy
Given PO
Undergo surgery
M D Anderson Cancer Center
Houston, Texas, United States
Feasibility of olaparib
Feasibility defined by number of subjects who are able to receive two cycles of PARP inhibition without unacceptable toxicity or disease progression (new disease or increase of CA125 from baseline \> 50%). Will be analyzed using descriptive statistics. Will be estimated using a 90% credible interval
Time frame: Up to 1 year
Response rate
For categorical endpoints, standard descriptive statistics, including frequency table and exact 95% confidence intervals will be computed using the Clopper-Pearson method.
Time frame: U to 1 year
Complete pathologic response
For categorical endpoints, standard descriptive statistics, including frequency table and exact 95% confidence intervals will be computed using the Clopper-Pearson method.
Time frame: For up to 1 year
Incidence of adverse events
For categorical endpoints, standard descriptive statistics, including frequency table and exact 95% confidence intervals will be computed using the Clopper-Pearson method.
Time frame: For up to 1 year
Symptom burden and health status
Will be assessed by the MD Anderson Symptom Inventory (MDASI) ."For categorical endpoints, standard descriptive statistics, including frequency table and exact 95% confidence intervals will be computed using the Clopper-Pearson method.
Time frame: For up to 1 year
Progression-free survival
Summarized using descriptive statistics, including Kaplan-Meier curve and estimates.
Time frame: Up to 1 year
Symptom burden and health status
Will be assessed by EuroQol 5-dimension. For categorical endpoints, standard descriptive statistics, including frequency table and exact 95% confidence intervals will be computed using the Clopper-Pearson method.
Time frame: For up to 1 year
Symptom burden and health status
Will be assessed by 5-level (EQ-5D-5L) instruments. For categorical endpoints, standard descriptive statistics, including frequency table and exact 95% confidence intervals will be computed using the Clopper-Pearson method.
Time frame: For up to 1 year
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