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Platinum-Refractory Fallopian Tube CarcinomaPhase 1/2NCT06393751

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

A Phase 1/2 study testing Bevacizumab, Biospecimen Collection and Computed Tomography in people with Platinum-Refractory Fallopian Tube Carcinoma and Platinum-Refractory Ovarian Carcinoma, run by National Cancer Institute (NCI).

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Bevacizumab, Biospecimen Collection and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
31 Oct 2025to 9 Feb 2028
Phase
Phase 1/2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 32Show fewer
  • 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:
  • Adjuvant/neoadjuvant therapy is counted as only 1 regimen in the absence of intervening progression.
  • Maintenance therapy (e.g., bevacizumab, poly adenosine diphosphate-ribose polymerase [PARP] inhibitor will be considered part of the preceding line of therapy [i.e., not counted independently])
  • Therapy changed due to toxicity in the absence of progression will be considered part of the same line (i.e., not counted independently)
  • Hormonal therapy will not be counted as a separate line of therapy
  • Age ≥ 18
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3
  • Platelets ≥ 100,000 cells/mm^3
  • Hemoglobin ≥ 8 g/dl
  • Creatinine ≤ institutional upper limit of normal (ULN), OR calculated creatinine clearance (CrCL) of ≥ 50 mL/min by the Cockcroft-Gault formula
  • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x ULN may be enrolled)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN
  • Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
  • No active infection requiring parental antibiotics
  • No evidence of intra-abdominal abscess, abdominal/pelvic fistula, gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or with drainage gastrostomy tube required. NOTE: required interval since last bowel obstruction: 30 day minimum for incomplete obstruction, resolved with conservative means; 6 months for fistula

Who cannot join

  • 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)

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Bevacizumab, Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging, Paclitaxel

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabBiological

    Also called ABP 215, ABP-215, ABP215, Alymsys

    Given IV

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • TolinapantDrug

    Also called ASTX 660, ASTX660, XIAP/cIAP1 Antagonist ASTX660

    Given PO

Study groups in NCT06393751
Study groupRoleWhat they receive
Phase I (paclitaxel, tolinapant, bevacizumab)ExperimentalPatients 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.
Receives: Biological: Bevacizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel; Drug: Tolinapant
Phase II, Arm I (paclitaxel, bevacizumab)Active comparatorPatients 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.
Receives: Biological: Bevacizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel
Phase II, Arm II (paclitaxel, tolinapant, bevacizumab)ExperimentalPatients 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.
Receives: Biological: Bevacizumab; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel; Drug: Tolinapant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: At 28 days

  2. 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.

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

Secondary outcomes (4)

  1. Incidence of adverse events (AEs)

    AEs will be defined as any untoward medical occurrence associated wtih the use of a drug in humans, whether or not considered drug related. AEs will be graded using NCI CTCAE v5.0. All AEs will be summarized.

    Measured: Up to 30 days after last dose of study treatment

  2. Overall survival (OS)

    OS will be defined as the time from randomization to death from any cause. The OS treatment hypothesis will be based on a logrank test, stratified by the factors specified at randomization. Comparisons of the OS distributions by treatment arm will be described using Kaplan-Meier methods. Treatment hazard ratio estimates and their 95% confidence intervals will be estimated using a multivariable proportional hazards model specified with main effects for the randomization treatment assignment and stratified by the factors declared at randomization.

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

  3. Objective response rate (ORR)

    ORR will be defined as the binomial proportion of evaluable patients with a best overall response of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors. The ORR estimates by treatment arm will be supported by their 2-sided, 95% Wilson-Score confidence intervals. The relative odds of response in the experimental arm will be estimated using a multivariable logistic regression model specified with main effects for the treatment groups and stratified by the stratification factors reported at baseline.

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

  4. Duration of response (DOR)

    DOR will be defined as the time from first documentation of either PR or CR until disease progression or death, whichever is observed first. Treatment group differences in response duration will be graphed using Kaplan-Meier methods and compared using logrank tests, stratified by the factors declared at randomization. The relative hazards of progression or death in each group will be estimated using similarly stratified proportional hazards regression model specified with main effects for the treatment indicator.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 May 2024
  2. Study start31 Oct 2025 (estimated)
  3. Primary completion9 Feb 2028 (estimated)
  4. Study completion9 Feb 2028 (estimated)

Why it stopped: Other - Protocol moved to Withdrawn

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06393751
Sponsor's protocol ID
NCI-2024-03344
Other IDs
NCI-2024-03344, NRG-GY034, NRG-GY034, U10CA180868
Status last verified
Jun 2025
First submitted
30 Apr 2024
Last updated
3 Jun 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

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