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

NCT06393751 | Withdrawn Phase 1 FDA Drug

• 3 other identifiers: NCI-2024-03344NRG-GY034U10CA180868
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

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

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicity (Phase I)

  Assessed using the Bayesian Optimal Interval design. Toxicity will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.

  At 28 days

• Progression free survival (PFS) (Phase II)

  The primary hypothesis test will be based on a logrank test, stratified on factors declared at randomization. The PFS hazard ratio will be estimated by Cox regression, stratified by factors declared at randomization. The treatment hazard ratio estimates and their 95% confidence intervals will be estimated using proportional hazards models specified to be consistent with the logrank tests.

  At randomization to progressive disease or death, assessed up to 5 years after completion of study treatment

Secondary Outcomes (4)

• Incidence of adverse events (AEs)

  Up to 30 days after last dose of study treatment

• Overall survival (OS)

  At randomization to death, assessed up to 5 years after completion of study treatment

• Objective response rate (ORR)

  At start of treatment to disease progression/recurrence, assessed up to 5 years after completion of treatment

• Duration of response (DOR)

  At first response to progression or death, assessed up to 5 years after completion of study treatment

Other Outcomes (4)

• Lack of cIAP1 expression

  Up to 5 years after completion of study treatment

• ORR (Phase I/Ib)

  Up to 5 years after completion of study treatment

• PFS (Phase I/Ib)

  Up to 6 months after starting treatment

Study Arms (3)

Phase I (paclitaxel, tolinapant, bevacizumab)

EXPERIMENTAL

Patients receive paclitaxel IV on days 1, 8 and 15, bevacizumab IV on days 1 and 15, and ASTX660 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, CT and MRI throughout the study.

Biological: Bevacizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel; Drug: Tolinapant

Phase II, Arm I (paclitaxel, bevacizumab)

ACTIVE COMPARATOR

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.

Biological: Bevacizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel

Phase II, Arm II (paclitaxel, tolinapant, bevacizumab)

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.

Biological: Bevacizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel; Drug: Tolinapant

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: ABP 215, ABP-215, ABP215, Alymsys, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF Monoclonal Antibody SIBP04, Anti-VEGF rhuMAb, Avastin, Avzivi, Aybintio, BAT 1706, BAT-1706, BAT1706, BAT1706 Biosimilar, Bevacizumab awwb, Bevacizumab Biosimilar ABP 215, Bevacizumab Biosimilar BAT1706, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MB02, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar Mvasi, Bevacizumab Biosimilar MYL-1402O, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar QL1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, Bevacizumab Biosimilar Zirabev, Bevacizumab-adcd, Bevacizumab-awwb, Bevacizumab-aybi, Bevacizumab-bvzr, Bevacizumab-equi, Bevacizumab-maly, Bevacizumab-onbe, Bevacizumab-tnjn, BP102, BP102 Biosimilar, CT P16, CT-P16, CTP16, Equidacent, FKB 238, FKB-238, FKB238, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, MB 02, MB-02, MB02, Mvasi, MYL-1402O, Onbevzi, Oyavas, PF 06439535, PF-06439535, PF06439535, QL1101, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501, SIBP 04, SIBP-04, SIBP04, Vegzelma, Zirabev

Phase I (paclitaxel, tolinapant, bevacizumab); Phase II, Arm I (paclitaxel, bevacizumab); Phase II, Arm II (paclitaxel, tolinapant, bevacizumab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Phase I (paclitaxel, tolinapant, bevacizumab); Phase II, Arm I (paclitaxel, bevacizumab); Phase II, Arm II (paclitaxel, tolinapant, bevacizumab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Phase I (paclitaxel, tolinapant, bevacizumab); Phase II, Arm I (paclitaxel, bevacizumab); Phase II, Arm II (paclitaxel, tolinapant, bevacizumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Phase I (paclitaxel, tolinapant, bevacizumab); Phase II, Arm I (paclitaxel, bevacizumab); Phase II, Arm II (paclitaxel, tolinapant, bevacizumab)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Phase I (paclitaxel, tolinapant, bevacizumab); Phase II, Arm I (paclitaxel, bevacizumab); Phase II, Arm II (paclitaxel, tolinapant, bevacizumab)

Tolinapant DRUG

Given PO

Also known as: ASTX 660, ASTX660, XIAP/cIAP1 Antagonist ASTX660

Phase I (paclitaxel, tolinapant, bevacizumab); Phase II, Arm II (paclitaxel, tolinapant, bevacizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically (histologically or cytologically) proven diagnosis of high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. Required: submission of pathology report
• Patients with the following histologic cell types are eligible:
• High grade serous
• Endometrioid, grade 3
• Clear cell
• Undifferentiated
• Mixed epithelial
• Carcinosarcoma
• Adenocarcinoma, not otherwise specified (NOS)
• Patients must be considered to have platinum-resistant or platinum-refractory recurrent ovarian cancer to be enrolled in this trial
• Platinum-resistant disease is defined as progression within \< 6 months from completion of platinum-based therapy. The date should be calculated from the last administered dose of platinum therapy
• Platinum-refractory disease is defined as progression within 30 days of completing the last dose of platinum during initial therapy. The date should be calculated from the last administered dose of platinum therapy
• Patients must have evaluable disease or measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured by CT or MRI. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI. Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation
• Patients with treated brain metastases are eligible if follow up brain imaging after central nervous system (CNS) directed therapy shows no evidence of progression
• Patients must have received ≥ 1 platinum-based therapy and not more than 5 prior lines of therapies. Notes:

You may not qualify if:

• Patients who have received prior weekly paclitaxel in a platinum-resistant setting
• Major surgical procedure within 28 days prior to registration, or anticipation of need for major surgical procedure during the study. Note: Placement of a vascular access device, thoracentesis, and/or paracentesis will not be considered major surgery
• Women who are pregnant or are unwilling to discontinue nursing
• Evidence of bleeding diathesis or clinically significant coagulopathy within the past 3 months. Patients are not excluded for past or current use of anticoagulation
• Uncontrolled hypertension (systolic blood pressure \[SBP\] \> 150 and/or diastolic blood pressure \[DBP\] \> 90)
• Patients currently taking and unwilling/unable to discontinue the use of drugs that are known to inhibit or induce P-glycoprotein (gp)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Specimen Handling; Magnetic Resonance Spectroscopy; Paclitaxel; Taxes; ASTX-660

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Kristen P Zeligs

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2024
• First Posted: May 1, 2024
• Study Start: October 31, 2025
• Primary Completion (Estimated): February 9, 2028
• Study Completion (Estimated): February 9, 2028
• Last Updated: June 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share