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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

ConditionsFallopian Tube CarcinosarcomaFallopian Tube Clear Cell AdenocarcinomaFallopian Tube Endometrioid AdenocarcinomaFallopian Tube Serous AdenocarcinomaOvarian CarcinosarcomaOvarian Clear Cell AdenocarcinomaOvarian Endometrioid AdenocarcinomaOvarian Serous AdenocarcinomaPrimary Peritoneal CarcinosarcomaPrimary Peritoneal Clear Cell AdenocarcinomaPrimary Peritoneal Endometrioid AdenocarcinomaPrimary Peritoneal Serous AdenocarcinomaRecurrent Fallopian Tube CarcinomaRecurrent Ovarian CarcinomaRecurrent Primary Peritoneal Carcinoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorRoswell Park Cancer Institute

About this trial

This phase II trial studies the effect of APL-2 when given in combination with either pembrolizumab or pembrolizumab and bevacizumab compared with bevacizumab alone in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent) and a buildup of fluid and cancer cells (malignant effusion). APL-2 may limit tumor progression, decrease malignant effusion production, and improve the immune system's response against cancer cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Giving APL-2 together with either pembrolizumab or pembrolizumab and bevacizumab may work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer and malignant effusion compared to bevacizumab alone.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age >= 18 years of age on day of signing informed consent

Recurrent epithelial ovarian/fallopian tube or primary peritoneal cancer (serous, clear cell, endometrioid, mixed or poorly differentiated or carcinosarcoma) based on imaging or synchronous primary ovarian and uterine cancer patients with any of the histology subtypes mentioned above regardless of platinum sensitivity, prior stage or number of prior treatment lines

Symptomatic ascites or pleural effusion or both requiring >= 1 drainage within 4-weeks of study entry or has a peritoneal/pleural drainage catheter in place to control symptoms

Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

Disqualifiers

Is currently receiving any additional cancer therapy or participating or used an investigational drug or device within 3 weeks of the first dose of treatment

Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment or, is taking any other medication that might affect immune function

Has active autoimmune disease that has required systemic treatment in the past 3 months (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment

Has an active infection requiring systemic therapy

Trial design

Design model

Parallel

Treatments tested in this trial

  • Bevacizumab

    Biological/Vaccine

    Given IV

  • Biopsy

    Procedure/Surgery

    Undergo tumor biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Pegcetacoplan

    Drug

    Given IV and SC

  • Pembrolizumab

    Biological/Vaccine

    Given IV

  • Questionnaire Administration

    Other intervention

    Ancillary studies

Treatment groups

60 Participants
are divided into 5 treatment groups
Group A: Cohort 2A-1 (pegcetacoplan, pembrolizumab)Experimental treatment 5 interventions
Group B: Cohort 2A-2 (pegcetacoplan, pembrolizumab, bevacizumab)Experimental treatment 6 interventions
Group C: Cohort 2B-1 (pegcetacoplan, pembrolizumab)Experimental treatment 5 interventions
Group D: Cohort 2B-2 (pegcetacoplan, pembrolizumab, bevacizumab)Experimental treatment 6 interventions
Group E: Cohort 2B-3 (bevacizumab)Experimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Incidence of adverse events (Phase 2a)

Toxicities and adverse events (as per Common Terminology Criteria for Adverse Events version 5.0) will be summarized by cohort and grade using frequencies and relative frequencies.

Time frame
Up to 30 days after last dose
2

Accumulation of effusion (Phase 2b)

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.

Time frame
Up to 3 years

Secondary outcomes

1

Overall survival

Will be summarized by cohort using standard Kaplan-Meier methods. As an exploratory analysis, the two dosing cohorts (cohorts A and B) may be compared to the control cohort (cohort C) compared using one-sided log-rank tests.

Time frame
From treatment until death or last follow-up, assessed up to 3 years
2

Progression free survival (PFS)

Will be summarized by cohort using standard Kaplan-Meier methods, where estimates of median PFS are obtained with 90% confidence intervals. As an exploratory analysis, the two dosing cohorts (cohorts A and B) may be compared to the control cohort (cohort C) compared using one-sided log-rank tests.

Time frame
From treatment initiation until disease progression, death, or last disease assessment (censored), assessed up to 3 years
3

Best response

Will be summarized by cohort using frequencies and relative frequencies.

Time frame
Up to 3 years
4

Overall response rate

Defined as the proportion of patients who have a partial or complete response to therapy. Will be estimated by cohort using 95% confidence intervals obtained by Jeffrey's prior method.

Time frame
Up to 3 years

Other outcomes

1

APL-2 pharmacokinetics (PK)/pharmacodynamics (PD) and immunological

APL-2 measures and immune markers will be summarized by cohort and time-point using the appropriate descriptive statistics. Each measure will be model as a function of cohort, time, their two-way interaction, and a random subject effect using a linear mixed model. Comparisons between cohorts within timepoint or between timepoints within cohort will be made using tests about the appropriate contrasts of model estimates. All model assumptions will be evaluated graphically, and transformations will be applied as appropriate.

Time frame
Baseline, day 1 of cycles 2, 3, and 7, and at end of treatment

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Roswell Park Cancer Institute

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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