Trials / Active Not Recruiting

Active Not RecruitingNCT02839707

Pegylated Liposomal Doxorubicin Hydrochloride With Atezolizumab and/or Bevacizumab in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

A Randomized, Phase II/III Study of Pegylated Liposomal Doxorubicin and CTEP-Supplied Atezolizumab Versus Pegylated Liposomal Doxorubicin, CTEP-Supplied Bevacizumab and CTEP-Supplied Atezolizumab Versus Pegylated Liposomal Doxorubicin and CTEP-Supplied Bevacizumab in Platinum Resistant Ovarian Cancer

Status: Active Not Recruiting
Phase: Phase 2 / Phase 3
Study type: Interventional
Enrollment: 444 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: Female
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase II/III trial studies how well pegylated liposomal doxorubicin hydrochloride with atezolizumab and/or bevacizumab work in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that has come back (recurrent). Chemotherapy drugs, such as pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, 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. It is not yet known which combination will work better in treating patients with ovarian, fallopian tube, or primary peritoneal cancer.

Detailed description

PRIMARY OBJECTIVES: I. Estimate the probability of a dose limiting toxicity (DLT) following cycle 1 of experimental regimens (pegylated liposomal doxorubicin hydrochloride \[pegylated liposomal doxorubicin\] \[PLD\] and atezolizumab and PLD/bevacizumab and atezolizumab). (Safety lead-in) II. Estimate and compare the hazard of first progression or death (progression free survival \[PFS\]) of each experimental regimen relative to the reference regimen, PLD and bevacizumab. (Phase II study) III. Estimate and compare the hazard of death and the hazard of first progression or death (PFS) of the experimental regimen relative to the reference regimen. (Phase III) (24-FEB-2021) SECONDARY OBJECTIVES: I. Estimate and compare the probabilities of response (objective response rate \[ORR\], either partial or complete response) defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria on each study regimen. (Phase II study) (24-FEB-2021) II. Estimate the frequency and severity of adverse events as classified and graded with Common Terminology Criteria for Adverse Events (CTCAE) in those patients who initiate their randomly assigned study treatment. (Phase II study) (03/19/2018) III. Estimate and compare ORR in each treatment group. (Phase III study) IV. Estimate the frequency and severity of adverse events in those patients who initiate their randomly assigned study treatment. (Phase III study) V. Estimate and compare mean patient reported outcome scores (PROs) as measured by National Comprehensive Cancer Network (NCCN)-Functional Assessment of Cancer Therapy (FACT) ovarian symptom index (NFOSI)-18 disease-related symptoms (DRS). (Phase III study) VI. Estimate and compare the treatment groups on the basis of the PROs: treatment side effects (TSE), function/well-being (FWB), fatigue (Functional Assessment of Chronic Illness Therapy \[FACIT\]-fatigue subscale) and abdominal discomfort (FACT/Gynecologic Oncology Group \[GOG\]-abdominal discomfort \[AD\] subscale). (Phase III study) (10/16/2017) TRANSLATIONAL SCIENCE OBJECTIVES: I. To determine whether biomarker levels in pre-treatment tissue, and pre- or on-treatment peripheral blood, and stool specimens are associated with ORR, PFS and/or overall survival (OS). II. Estimate pre-treatment PD-L1 expression on tumor cells measured by quantitative immunohistochemistry (IHC), and determine whether it is associated with the duration of PFS or overall survival. (Integrated Biomarker) III. Analysis of T cell receptor (TCR) repertoires by deep sequencing of peripheral blood samples. (Exploratory Biomarkers \[10/16/2017\]) IV. Tumor "immunogenicity" as determined by the neo-antigen landscape and characterization of the tumor microenvironment using next-generation sequencing, including but not limited to whole exome sequencing and/or RNA sequencing. (Exploratory Biomarkers \[10/16/2017\]) V. Microbiome analysis via stool sampling. (Exploratory Biomarkers \[10/16/2017\]) VI. To determine whether changes in quantitative biomarker parameters after the first 6 and 12 weeks of therapy predict ORR, PFS and/or OS. OUTLINE: Patients will be randomized to 1 of 3 arms. ARM I: Patients receive pegylated liposomal doxorubicin hydrochloride intravenously (IV) over 60 minutes on day 1 and atezolizumab IV over 30-60 minutes on days 1 and 15. (Closed to accrual as of February 09, 2021) ARM II: Patients receive pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1, bevacizumab IV over 30-90 minutes on days 1 and 15, and atezolizumab IV over 30-60 minutes on days 1 and 15. Patients also undergo computed tomography (CT) on study. ARM III: Patients receive pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 and bevacizumab IV over 30-90 minutes on days 1 and 15. Patients also undergo CT on study. In all arms, cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 2 years, and then every 6 months for up to 3 years.

Conditions

Interventions

Type	Name	Description
DRUG	Atezolizumab	Given IV
BIOLOGICAL	Bevacizumab	Given IV
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Pegylated Liposomal Doxorubicin Hydrochloride	Given IV
OTHER	Quality-of-Life Assessment	Ancillary studies

Timeline

Start date: 2017-06-23
Primary completion: 2023-05-09
Completion: 2026-03-31
First posted: 2016-07-21
Last updated: 2026-04-13
Results posted: 2025-03-04

Locations

922 sites across 2 countries: United States, Puerto Rico

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT02839707. Inclusion in this directory is not an endorsement.