Olaparib and Entinostat in Patients With Recurrent, Platinum-Refractory, Resistant Ovarian, Primary Peritoneal, Fallopian Tube Cancers
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|ClinicalTrials.gov Identifier: NCT03924245|
Recruitment Status : Suspended (Pending site logistics)
First Posted : April 23, 2019
Last Update Posted : May 14, 2020
|Condition or disease||Intervention/treatment||Phase|
|Fallopian Tube Cancer Fallopian Tube Carcinosarcoma Fallopian Tube Clear Cell Adenocarcinoma Fallopian Tube Endometrioid Adenocarcinoma High Grade Fallopian Tube Serous Adenocarcinoma High Grade Ovarian Serous Adenocarcinoma Ovarian Carcinosarcoma Ovarian Clear Cell Adenocarcinoma Ovarian Endometrioid Adenocarcinoma Primary Peritoneal Serous Adenocarcinoma Recurrent Endometrial Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma||Drug: Entinostat Drug: Olaparib||Phase 1 Phase 2|
I. Determine the maximum tolerated dose (MTD) for the combination of olaparib and entinostat in the treatment of recurrent, platinum-refractory or resistant high-grade serous carcinoma of the ovary, fallopian tube or peritoneum. (Phase I) II. Determine the objective response rate in patients with recurrent, platinum-refractory or resistant, homologous repair proficient (HRP) high-grade carcinoma of the ovary, fallopian tube or peritoneum treated with the combination of olaparib and entinostat at the recommended phase 2 dose, as determined in phase I of this trial. (Phase II)
I. Assess the safety and tolerability of the combination of olaparib and entinostat in patients with recurrent, platinum-refractory or resistant high-grade serous carcinoma of the ovary, fallopian tube, or peritoneum. (Phase I) II. Further assess the nature and degree of toxicity of olaparib and entinostat in this cohort of patients. (Phase II) III. Determine the clinical benefit rate (CBR) (complete response [CR] + partial response [PR] + stable disease [SD]) as assessed at the time of best response to therapy). (Phase II) IV. Determine the progression free (PFS) and overall survival (OS). (Phase II) V. Determine the duration of response (DoR). (Phase II)
I. Assess the correlation between the Myriad myChoice homologous recombination pathway deficiency (HRD) score and the response to treatment.
II. Assess the degree of deoxyribonucleic acid (DNA) damage in circulating tumor cells and tumor biopsies (optional) after cycle 2 and at the end of treatment by phosphorylated (p)HAX2 and PAR and correlate with the response to treatment.
III. Assess baseline cyclin E amplification in ovarian tumors by fluorescence in situ hybridization (FISH) and correlate with response to treatment.
IV. Assess the expression of ki67/mib1 as a marker of cell proliferation in circulating tumor cells and in tumor biopsy specimens (optional) after cycle 2 of therapy and at the end of treatment and correlate with response to treatment.
V. Measure cyclin E1, CDK2, E2F1, and BRD expression by immunohistochemistry in circulating tumor cells and in tumor biopsy specimens (optional) after cycle 2 of therapy and at the end of treatment and correlate with response to treatment.
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Patients receive entinostat orally (PO) 1 week before starting combination therapy (day -7). Patients then receive entinostat PO on days 1, 8, 15, and 22, and olaparib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression and unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||73 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of Olaparib With Entinostat in the Treatment of Recurrent, Platinum-Refractory or Resistant, Homologous Recombination Repair Proficient Ovarian, Primary Peritoneal, and Fallopian Tube Cancers|
|Actual Study Start Date :||September 18, 2019|
|Estimated Primary Completion Date :||September 2023|
|Estimated Study Completion Date :||September 2025|
Experimental: Treatment (entinostat, olaparib)
Patients receive entinostat PO 1 week before starting combination therapy (day -7). Patients then receive entinostat PO on days 1, 8, 15, and 22, olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression and unacceptable toxicity
Given by mouth
Given by mouth
- Maximum tolerated dose (phase I) [ Time Frame: 28 days ]
- Objective response rate (phase II) [ Time Frame: Approximately 60 days ]
- Clinical benefit rate [ Time Frame: 3 years ]
- Best overall response [ Time Frame: 3 years ]
- Progression free survival [ Time Frame: 3 years ]
- Overall survival [ Time Frame: 3 years ]
- Duration of response [ Time Frame: 3 years ]
- Incidence of adverse events per national Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [ Time Frame: Up to 30 days after treatment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03924245
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Marta Crispens, MD||Vanderbilt Medical Center|