Pembrolizumab, Bevacizumab, and Cyclophosphamide in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
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|ClinicalTrials.gov Identifier: NCT02853318|
Recruitment Status : Completed
First Posted : August 2, 2016
Results First Posted : November 6, 2020
Last Update Posted : October 6, 2021
|Condition or disease||Intervention/treatment||Phase|
|Fallopian Tube Clear Cell Adenocarcinoma Fallopian Tube Endometrioid Adenocarcinoma Fallopian Tube Mucinous Adenocarcinoma Fallopian Tube Serous Adenocarcinoma Ovarian Clear Cell Adenocarcinoma Ovarian Endometrioid Adenocarcinoma Ovarian Mucinous Adenocarcinoma Ovarian Serous Adenocarcinoma Primary Peritoneal Serous Adenocarcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Undifferentiated Fallopian Tube Carcinoma Undifferentiated Ovarian Carcinoma||Biological: Bevacizumab Drug: Cyclophosphamide Other: Laboratory Biomarker Analysis Biological: Pembrolizumab||Phase 2|
I. To evaluate improvement in progression-free survival for patients treated with anti-programmed cell death 1 (anti-PD1) pembrolizumab in combination with intravenous (IV) bevacizumab and oral metronomic cyclophosphamide as compared to patients treated with other second line chemotherapeutic agents.
I. To obtain pilot data on clinical response rates using both Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and immune related response criteria (irRECIST).
II. To obtain data on changes in tumor microenvironment prior to and subsequent to therapy and, to screen for potential biomarkers to predict clinical benefit.
III. To determine the safety and tolerability of the treatment combination in the study population.
IV. To evaluate overall survival in patients treated with anti-PD1 pembrolizumab in combination with IV bevacizumab and oral metronomic cyclophosphamide.
V. To assess the impact of the combination of anti-PD1 pembrolizumab, IV bevacizumab and oral metronomic cyclophosphamide on anti-tumor immune responses in ovarian cancer.
Patients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1 and cyclophosphamide orally (PO) once daily (QD) on days 1-21. Treatment repeats every 3 weeks for up to 12 months (or 17 courses) in the absence of disease progression or unacceptable toxicity. Patients without evidence of disease progression may continue treatment in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, then every 3 months for 1 year, and every 12 weeks and 6 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Evaluation of Pembrolizumab in Combination With IV Bevacizumab and Oral Metronomic Cyclophosphamide in the Treatment of Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer|
|Actual Study Start Date :||September 1, 2016|
|Actual Primary Completion Date :||June 27, 2019|
|Actual Study Completion Date :||June 30, 2021|
Experimental: Treatment (pembrolizumab, bevacizumab, cyclophosphamide)
Patients receive pembrolizumab IV over 30 minutes and bevacizumab IV over 30-90 minutes on day 1 and cyclophosphamide PO QD on days 1-21. Treatment repeats every 3 weeks for up to 17 courses in the absence of disease progression or unacceptable toxicity. Patients without evidence of disease progression may continue treatment in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events [ Time Frame: Up to 1 year ]The highest observed adverse event will be tabulated by grade across all dose levels and cycles.
- Progression-free Survival (PFS) [ Time Frame: Time from the start of the study treatment until PFS event, assessed up to 1 year after the last subject enrolls ]Will be summarized using standard Kaplan-Meier methods, with estimates of median survival and given survival rates will be obtained with 90% confidence intervals.
- Duration of Overall Survival [ Time Frame: Up to 1 year after enrollment of the last subject ]Will be summarized using standard Kaplan-Meier methods, with estimates of median survival and given survival rates will be obtained with 90% confidence intervals.
- An Anti-tumor Immune Response in Circulation and Tumor Tissue [ Time Frame: Up to 1 year ]Assessed with immunohistochemistry (IHC), Nannostring, Flow Cytometry and Luminex assay.
- Objective Tumor Response Assessed by Modified RECIST Version 1.1 Criteria [ Time Frame: Up to 6 months after enrollment start of treatment ]
Frequency of response will be summarized with a 90% confidence interval.
An objective response is defined as a CR or PR, while a non-responder is defined as a SD or PD.
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): NCT02853318
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Principal Investigator:||Emese Zsiros||Roswell Park Cancer Institute|