NCT06393751

Testing the Addition of ASTX660 (Tolinapant) to the Usual Chemotherapy Treatment (Paclitaxel With or Without Bevacizumab) in Patients With Recurrent Ovarian Cancer

A Randomized Phase 1/2 Trial Evaluating the Addition of Tolinapant to Weekly Paclitaxel With or Without Bevacizumab in Patients With Recurrent Epithelial Ovarian Cancer

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial tests the safety, best dose and effectiveness of adding tolinapant (ASTX660) to paclitaxel with or without bevacizumab in treating patients with ovarian cancer that has come back after a period of improvement (recurrent). Tolinapant may stop the growth of tumor cells by blocking proteins, such as XIAP and cIAP1, that promote the growth of tumor cells and increase resistance to chemotherapy. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to the tumor. This may slow the growth and spread of tumor cells. Adding ASTX660 to paclitaxel with or without bevacizumab may be safe, tolerable and/or effective in treating patients with recurrent ovarian cancer.

Detailed description

PRIMARY OBJECTIVES: I. To assess the safety and tolerability of adding ASTX660 (tolinapant) to a regimen of weekly paclitaxel with bevacizumab. (Phase I) II. To determine the recommended phase 2 dose (RP2D) for the combination of ASTX660 (tolinapant) and weekly paclitaxel with bevacizumab. (Phase I) III. To assess the efficacy of adding ASTX660 (tolinapant) to weekly paclitaxel, with or without bevacizumab (investigator choice), as measured by progression free survival (PFS). (Phase II) SECONDARY OBJECTIVES: I. To assess the objective response rate (ORR) of the addition of ASTX660 (tolinapant) to weekly paclitaxel with or without bevacizumab as compared to weekly paclitaxel with or without bevacizumab. II. To assess overall survival. EXPLORATORY OBJECTIVE: I. To explore whether lack of cIAP1 expression results in no benefit for the addition of ASTX660 (tolinapant) to weekly paclitaxel +/- bevacizumab. OUTLINE: This is a phase I, dose escalation study of ASTX660 and paclitaxel with or without bevacizumab followed by a dose expansion study. The phase II study will follow completion of the phase I study. PHASE I: Patients receive paclitaxel intravenously (IV) on days 1, 8 and 15, bevacizumab IV on days 1 and 15, and ASTX660 orally (PO) on days 1-7 and 15-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, computed tomography (CT) and magnetic resonance imaging (MRI) throughout the study. PHASE II: Patients are randomized to 1 of 2 arms. ARM I (CONTROL): Patients receive paclitaxel IV on days 1, 8, and 15 of each cycle. Patients may also receive bevacizumab IV on days 1 and 15 of each cycle per provider. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT and MRI throughout the study. ARM II (EXPERIMENTAL): Patients receive paclitaxel IV on days 1, 8, and 15 and ASTX660 PO on days 1-7 and 15-21 of each cycle. Patients may also receive bevacizumab IV on days 1 and 15 of each cycle per provider. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT and MRI throughout the study. After completion of study treatment, patients are followed up every 3 months for 2 years then every 6 months for 3 years.

Conditions

• Platinum-Refractory Fallopian Tube Carcinoma
• Platinum-Refractory Ovarian Carcinoma
• Platinum-Refractory Primary Peritoneal Carcinoma
• Recurrent Fallopian Tube Adenocarcinoma
• Recurrent Fallopian Tube Carcinosarcoma
• Recurrent Fallopian Tube Clear Cell Adenocarcinoma
• Recurrent Fallopian Tube High Grade Serous Adenocarcinoma
• Recurrent Fallopian Tube Undifferentiated Carcinoma
• Recurrent High Grade Endometrioid Adenocarcinoma
• Recurrent Ovarian Adenocarcinoma
• Recurrent Ovarian Carcinosarcoma
• Recurrent Ovarian Clear Cell Adenocarcinoma
• Recurrent Ovarian High Grade Serous Adenocarcinoma
• Recurrent Ovarian Seromucinous Carcinoma
• Recurrent Ovarian Undifferentiated Carcinoma
• Recurrent Platinum-Resistant Fallopian Tube Carcinoma
• Recurrent Platinum-Resistant Ovarian Carcinoma
• Recurrent Platinum-Resistant Primary Peritoneal Carcinoma
• Recurrent Primary Peritoneal Adenocarcinoma
• Recurrent Primary Peritoneal Carcinosarcoma
• Recurrent Primary Peritoneal Clear Cell Adenocarcinoma
• Recurrent Primary Peritoneal High Grade Serous Adenocarcinoma
• Recurrent Primary Peritoneal Undifferentiated Carcinoma

Interventions

Type	Name	Description
BIOLOGICAL	Bevacizumab	Given IV
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
DRUG	Paclitaxel	Given IV
DRUG	Tolinapant	Given PO

Timeline

• Start date: 2025-10-31
• Primary completion: 2028-02-09
• Completion: 2028-02-09
• First posted: 2024-05-01
• Last updated: 2025-06-03

Regulatory

• FDA-regulated drug study