Condition or disease | Intervention/treatment | Phase |
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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 |
PRIMARY OBJECTIVES:
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)
SECONDARY OBJECTIVES:
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)
EXPLORATORY OBJECTIVES:
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 |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Arm | Intervention/treatment |
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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
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Drug: Entinostat
Given by mouth
Drug: Olaparib Given by mouth
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Gender Based Eligibility: | Yes |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
Estimated creatinine clearance = (140-age [years]) x weight (kg) (x 0.85) serum creatinine (mg/dL) x 72
Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. Postmenopausal is defined as:
The patient must provide separate informed consent to obtain the optional tumor biopsy.
If a patient declines to participate in the optional tissue biopsy, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study.
Exclusion Criteria:
Contact: Vanderbilt-Ingram Service for Timely Access | 800-811-8480 | cip@vanderbilt.edu |
United States, Tennessee | |
Vanderbilt-Ingram Cancer Center | Recruiting |
Nashville, Tennessee, United States, 37232 | |
Contact: Vanderbilt-Ingram Service Vanderbilt-Ingram Service 800-811-8480 cip@vanderbilt.edu | |
Principal Investigator: Marta Crispesn, MD |
Principal Investigator: | Marta Crispens, MD | Vanderbilt Medical Center |
Tracking Information | |||||||
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First Submitted Date ICMJE | April 18, 2019 | ||||||
First Posted Date ICMJE | April 23, 2019 | ||||||
Last Update Posted Date | June 5, 2020 | ||||||
Actual Study Start Date ICMJE | September 18, 2019 | ||||||
Estimated Primary Completion Date | September 2023 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Olaparib and Entinostat in Patients With Recurrent, Platinum-Refractory, Resistant Ovarian, Primary Peritoneal, Fallopian Tube Cancers | ||||||
Official Title ICMJE | 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 | ||||||
Brief Summary | This phase I/II trial studies the side effects and best dose of olaparib and entinostat and to see how well they work in treating patients with ovarian, primary peritoneal, or fallopian tube cancers that have come back or do not respond to platinum-based chemotherapy. Olaparib and entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. | ||||||
Detailed Description |
PRIMARY OBJECTIVES: 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) SECONDARY OBJECTIVES: 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) EXPLORATORY OBJECTIVES: 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. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | 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
Interventions:
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Recruiting | ||||||
Estimated Enrollment ICMJE |
73 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | September 2025 | ||||||
Estimated Primary Completion Date | September 2023 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Estimated creatinine clearance = (140-age [years]) x weight (kg) (x 0.85) serum creatinine (mg/dL) x 72
The patient must provide separate informed consent to obtain the optional tumor biopsy. If a patient declines to participate in the optional tissue biopsy, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study. Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03924245 | ||||||
Other Study ID Numbers ICMJE | VICC GYN 1842 NCI-2019-02322 ( Registry Identifier: NCI, Clinical Trials Reporting Program ) |
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Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Marta Crispens, MD, Vanderbilt-Ingram Cancer Center | ||||||
Study Sponsor ICMJE | Vanderbilt-Ingram Cancer Center | ||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Vanderbilt-Ingram Cancer Center | ||||||
Verification Date | June 2020 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |