Repurposing Atovaquone for the Treatment of Platinum-Resistant Ovarian Cancer

Phase 2

Recruiting

• Conditions: Ovarian High Grade Serous Adenocarcinoma; Platinum-Resistant Ovarian Carcinoma
• Interventions: Drug: Atovaquone; Procedure: Biopsy; Procedure: Computed Tomography; Procedure: Paracentesis

• Registration Number: NCT05998135
• Lead Sponsor: Emory University

Brief Summary

This phase II trial test tests how well repurposing atovaquone works in treating patients with platinum-resistant ovarian cancer. Atovaquone is used for the treatment or prevention of certain infections. Atovaquone is in a class of medications called antiprotozoal agents. It works by stopping the growth of certain types of protozoa that can cause pneumonia. Giving atovaquone may be effective in treating platinum-resistant ovarian cancer and result in improved outcomes compared to standard chemotherapy regimens.

Detailed Description

PRIMARY OBJECTIVE:

I. To determine progression free survival of twenty-eight patients with platinum-resistant ovarian cancer treated with atovaquone.

SECONDARY OBJECTIVES:

I. To determine clinical benefit rate (complete response, partial response or stable disease) at six months.

II. To determine overall survival. III. To quantitate the on-target STAT3 inhibitory effect of atovaquone on STAT3-dependent gene transcription.

IV. To quantitate changes of the tumor immune infiltrate by inhibition of STAT3 with atovaquone.

OUTLINE:

Patients receive atovaquone orally (PO) on study. Patients also undergo computed tomography (CT) and biopsy or paracentesis throughout the study.

After completion of study treatment, patients are followed up for 30 days and then every 6 month thereafter.

Study Timeline

• Study First Submitted: 2023-08-11
• Study First Submitted QC: 2023-08-11
• Study First Posted: 2023-08-18
• Study Start: 2023-11-09
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-06
• Last Update Posted: 2024-08-07
• Primary Completion: 2025-06-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 28

Inclusion Criteria

• Patients with platinum-resistant, high-grade serous ovarian cancer, defined as disease progression within six months of completion of their last platinum-based chemotherapy
• Patients must maintain Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• There will be no limitations on number of prior lines of therapy
• Trial is open to non-English speaking patients
• Trial is open to patients referred from community practice

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Exclusion Criteria

• Patients who are < 18 years old
• Patients who are pregnant or breastfeeding (due to cancer of their reproductive organs, patients enrolled in the trial are unable to conceive)
• Patients who are incarcerated
• Patients who are unable to provide consent / lack decision-making capacity

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (atovaquone)	Biopsy	Patients receive atovaquone PO on study. Patients also undergo CT and biopsy or paracentesis throughout the study.
Treatment (atovaquone)	Computed Tomography	Patients receive atovaquone PO on study. Patients also undergo CT and biopsy or paracentesis throughout the study.
Treatment (atovaquone)	Paracentesis	Patients receive atovaquone PO on study. Patients also undergo CT and biopsy or paracentesis throughout the study.
Treatment (atovaquone)	Atovaquone	Patients receive atovaquone PO on study. Patients also undergo CT and biopsy or paracentesis throughout the study.

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	From initiation of atovaquone to progression or death, assessed up to 1 year	Will be estimated using the Kaplan-Meier method, and a 95% confidence interval for median PFS will be estimated using the Brookmeyer-Crowley approach.

Secondary Outcome Measures

Name	Time	Method
Clinical benefit rate	At 6 months	Clinical benefit rate is defined as complete response, partial response, and/or stable disease at six months. Clinical response will be assessed every 6 weeks for the first 24 months and every 12 weeks thereafter using Response Evaluation Criteria in Solid Tumors 1.1 criteria. Will be estimated as a proportion, with an exact 95% confidence interval estimated using the Clopper-Pearson method.
Overall survival (OS)	From diagnosis to death from any cause, where patients who are alive will be censored at last follow-up date, assessed up to 1 year	OS will be estimated using the Kaplan-Meier method, and median survival will be calculated. A 95% confidence interval will be estimated using the Brookmeyer-Crowley approach.
Incidence of adverse events	Up to 30 days	Safety will be determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Frequencies and percentages will be used to summarize safety events.

Trial Locations

Locations (1)

Emory University Hospital/Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States