Condition or disease | Intervention/treatment | Phase |
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Fallopian Tube Carcinosarcoma Fallopian Tube Adenocarcinoma Fallopian Tube Serous Adenocarcinoma Ovarian Carcinosarcoma Ovarian Clear Cell Adenocarcinoma Ovarian Endometrioid Adenocarcinoma Ovarian Serous Adenocarcinoma Primary Peritoneal Adenocarcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma | Biological: Bevacizumab Biological: Pegcetacoplan Biological: Pembrolizumab Other: Quality-of-Life Assessment Other: Questionnaire Administration | Phase 2 |
PRIMARY OBJECTIVES:
I. Determine the safety of APL-2 (Pegcetacoplan) alone and in combination with pembrolizumab, and APL-2 in combination with both bevacizumab and pembrolizumab in patients with recurrent ovarian cancer with symptomatic malignant effusion II. Effect of therapy on of malignant effusion measured by total volume of effusion drained every 3 weeks (patient diary and/or drained volume).
SECONDARY OBJECTIVES:
I. Determine progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and overall survival (OS) II. Changes in quality of life measures during the clinical trial
This is a single center, randomized, Phase 2 clinical trial of APL-2 in combination with Pembrolizumab or in combination with Bevacizumab and Pembrolizumab vs. Bevacizumab alone in patients with recurrent ovarian/fallopian tube/primary peritoneal cancer and persistent malignant effusions.
A safety-lead in cohort of 3-5 patients, (patients will receive APL-2 alone for 2 weeks prior to adding pembrolizumab or pembrolizumab and bevacizumab) will be recruited to assess the safety of APL-2 alone, determine PK/PD levels is serum and malignant effusion and to test the short-term single-agent APL-2 effects on malignant effusion. If no concerning treatment limiting toxicity signal is seen, the randomized expansion cohorts (2B) are allowed to start. Patients will be randomized to 1 of 3 cohorts (2 experimental arms and 1 standard of care control arm).
COHORT 2B-1: APL-2 (Pegcetacoplan) and pembrolizumab (experimental arm)
COHORT 2B-2: Pegcetacoplan, pembrolizumab and bevacizumab (experimental arm)
COHORT 2B-3: Bevacizumab only (control arm)
Treatment repeats every 3 weeks and treatment will continue until disease progression, patient withdrawal or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks thereafter up to 3 years.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 40 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Randomized Phase 2 Trial of APL-2 With Pembrolizumab vs. APL-2 With Pembrolizumab and Bevacizumab vs. Bevacizumab Alone in Patients With Recurrent Ovarian Cancer and Persistent Malignant Effusion |
Estimated Study Start Date : | December 1, 2021 |
Estimated Primary Completion Date : | December 1, 2024 |
Estimated Study Completion Date : | December 1, 2025 |
Arm | Intervention/treatment |
---|---|
Experimental: Cohort 2B-1 (pegcetacoplan, pembrolizumab) |
Biological: Pegcetacoplan
Given IV (only for loading dose) and SC
Other Names:
Biological: Pembrolizumab Given IV
Other Names:
Other: Questionnaire Administration Ancillary studies
|
Experimental: Cohort 2B-2 (pegcetacoplan, pembrolizumab, bevacizumab) |
Biological: Bevacizumab
Given IV
Other Names:
Biological: Pegcetacoplan Given IV (only for loading dose) and SC
Other Names:
Biological: Pembrolizumab Given IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment
Other: Questionnaire Administration Ancillary studies
|
Experimental: Cohort 2B-3 (bevacizumab) |
Biological: Bevacizumab
Given IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment
Other: Questionnaire Administration Ancillary studies
|
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, New York | |
Roswell Park Cancer Institute | |
Buffalo, New York, United States, 14263 | |
Contact: Emese Zsiros 716-845-8337 Emese.Zsiros@roswellpark.org | |
Principal Investigator: Emese Zsiros |
Principal Investigator: | Emese Zsiros | Roswell Park Cancer Institute |
Tracking Information | |||||||
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First Submitted Date ICMJE | May 27, 2021 | ||||||
First Posted Date ICMJE | June 9, 2021 | ||||||
Last Update Posted Date | November 11, 2021 | ||||||
Estimated Study Start Date ICMJE | December 1, 2021 | ||||||
Estimated Primary Completion Date | December 1, 2024 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Accumulation of effusion (Phase 2b) [ Time Frame: Up to 3 years ] Will determine the effect of therapy on accumulation of effusion measured by total volume removed every 3 weeks. The change in accumulation of effusion (relative to pre-treatment) will be modeled as a function of cohort, time-point, their two-way interaction, baseline levels, and a random subject effect using a linear mixed model. The change will be compared: a) over-time within each cohort, and b) between the control cohort (cohort C) and each dosing cohort (cohorts A and B) using two-sided Bonferroni or Dunnet adjusted tests about the appropriate contrasts of model estimates. The model assumptions will be evaluated graphically, and transformations will be applied as appropriate.
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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 | APL-2 and Pembrolizumab Versus APL-2, Pembrolizumab and Bevacizumab Versus Bevacizumab Alone for the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer and Malignant Effusion | ||||||
Official Title ICMJE | Randomized Phase 2 Trial of APL-2 With Pembrolizumab vs. APL-2 With Pembrolizumab and Bevacizumab vs. Bevacizumab Alone in Patients With Recurrent Ovarian Cancer and Persistent Malignant Effusion | ||||||
Brief Summary | This phase randomized phase 2 clinical trial to study the safety and effect of C3 complement inhibitor APL-2 (Pegcetacoplan) alone and in combination with Pembrolizumab, as well as APL-2 in combination with both Bevacizumab and Pembrolizumab in patients with recurrent ovarian, fallopian tube or primary peritoneal cancer with symptomatic malignant effusion (ascites or pleural effusion). APL-2 (Pegcetacoplan) is the lead drug in the class of compstatins, which are synthetic peptides that bind to C3 and inhibit the classical and alternative pathway C3 convertase formation required for complement activation. The rationale for using APL-2 in recurrent ovarian, fallopian tube and primary peritoneal cancer with recurrent malignant effusion is two-fold: (1) to decrease the immune system suppressing neutrophil cell accumulation in tumor tissue thereby making immune check point blockade more effective; and (2) to prevent generation of anaphylatoxins (C3a, C4a, and C5a) that increase vessel permeability and lead to malignant fluid accumulation. The current standard for palliation of ascites and/or pleural effusions in recurrent ovarian/fallopian tube/primary peritoneal cancer involves the use of bevacizumab alone or combined with a chemotherapy drug as well as repeated drainage of the fluid. | ||||||
Detailed Description |
PRIMARY OBJECTIVES: I. Determine the safety of APL-2 (Pegcetacoplan) alone and in combination with pembrolizumab, and APL-2 in combination with both bevacizumab and pembrolizumab in patients with recurrent ovarian cancer with symptomatic malignant effusion II. Effect of therapy on of malignant effusion measured by total volume of effusion drained every 3 weeks (patient diary and/or drained volume). SECONDARY OBJECTIVES: I. Determine progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and overall survival (OS) II. Changes in quality of life measures during the clinical trial This is a single center, randomized, Phase 2 clinical trial of APL-2 in combination with Pembrolizumab or in combination with Bevacizumab and Pembrolizumab vs. Bevacizumab alone in patients with recurrent ovarian/fallopian tube/primary peritoneal cancer and persistent malignant effusions. A safety-lead in cohort of 3-5 patients, (patients will receive APL-2 alone for 2 weeks prior to adding pembrolizumab or pembrolizumab and bevacizumab) will be recruited to assess the safety of APL-2 alone, determine PK/PD levels is serum and malignant effusion and to test the short-term single-agent APL-2 effects on malignant effusion. If no concerning treatment limiting toxicity signal is seen, the randomized expansion cohorts (2B) are allowed to start. Patients will be randomized to 1 of 3 cohorts (2 experimental arms and 1 standard of care control arm). COHORT 2B-1: APL-2 (Pegcetacoplan) and pembrolizumab (experimental arm) COHORT 2B-2: Pegcetacoplan, pembrolizumab and bevacizumab (experimental arm) COHORT 2B-3: Bevacizumab only (control arm) Treatment repeats every 3 weeks and treatment will continue until disease progression, patient withdrawal or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks thereafter up to 3 years. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 2 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel 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 |
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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 | Not yet recruiting | ||||||
Estimated Enrollment ICMJE |
40 | ||||||
Original Estimated Enrollment ICMJE |
50 | ||||||
Estimated Study Completion Date ICMJE | December 1, 2025 | ||||||
Estimated Primary Completion Date | December 1, 2024 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
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 | |||||||
Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT04919629 | ||||||
Other Study ID Numbers ICMJE | I 798120 NCI-2021-04265 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) I 798120 ( Other Identifier: Roswell Park Cancer Institute ) |
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Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||||
Responsible Party | Roswell Park Cancer Institute | ||||||
Study Sponsor ICMJE | Roswell Park Cancer Institute | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE |
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PRS Account | Roswell Park Cancer Institute | ||||||
Verification Date | November 2021 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |