Trial Title:
Testing the Addition of ASTX660 (Tolinapant) to the Usual Chemotherapy Treatment (Paclitaxel With or Without Bevacizumab) in Patients With Recurrent Ovarian Cancer
NCT ID:
NCT06393751
Condition:
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
Conditions: Official terms:
Carcinoma
Adenocarcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Cystadenocarcinoma, Serous
Fallopian Tube Neoplasms
Carcinoma, Endometrioid
Carcinosarcoma
Mixed Tumor, Mullerian
Adenocarcinoma, Clear Cell
Recurrence
Paclitaxel
Bevacizumab
Albumin-Bound Paclitaxel
Antineoplastic Agents, Immunological
Endothelial Growth Factors
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunoglobulin G
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Bevacizumab
Description:
Given IV
Arm group label:
Phase I (paclitaxel, tolinapant, bevacizumab)
Arm group label:
Phase II, Arm I (paclitaxel, bevacizumab)
Arm group label:
Phase II, Arm II (paclitaxel, tolinapant, bevacizumab)
Other name:
ABP 215
Other name:
ABP-215
Other name:
ABP215
Other name:
Alymsys
Other name:
Anti-VEGF
Other name:
Anti-VEGF Humanized Monoclonal Antibody
Other name:
Anti-VEGF Monoclonal Antibody SIBP04
Other name:
Anti-VEGF rhuMAb
Other name:
Avastin
Other name:
Aybintio
Other name:
BAT 1706
Other name:
BAT-1706
Other name:
BAT1706
Other name:
BAT1706 Biosimilar
Other name:
Bevacizumab awwb
Other name:
Bevacizumab Biosimilar ABP 215
Other name:
Bevacizumab Biosimilar BAT1706
Other name:
Bevacizumab Biosimilar BEVZ92
Other name:
Bevacizumab Biosimilar BI 695502
Other name:
Bevacizumab Biosimilar CBT 124
Other name:
Bevacizumab Biosimilar CT-P16
Other name:
Bevacizumab Biosimilar FKB238
Other name:
Bevacizumab Biosimilar GB-222
Other name:
Bevacizumab Biosimilar HD204
Other name:
Bevacizumab Biosimilar HLX04
Other name:
Bevacizumab Biosimilar IBI305
Other name:
Bevacizumab Biosimilar LY01008
Other name:
Bevacizumab Biosimilar MIL60
Other name:
Bevacizumab Biosimilar Mvasi
Other name:
Bevacizumab Biosimilar MYL-1402O
Other name:
Bevacizumab Biosimilar QL 1101
Other name:
Bevacizumab Biosimilar QL1101
Other name:
Bevacizumab Biosimilar RPH-001
Other name:
Bevacizumab Biosimilar SCT501
Other name:
Bevacizumab Biosimilar Zirabev
Other name:
Bevacizumab-adcd
Other name:
Bevacizumab-awwb
Other name:
Bevacizumab-aybi
Other name:
Bevacizumab-bvzr
Other name:
Bevacizumab-equi
Other name:
Bevacizumab-maly
Other name:
Bevacizumab-onbe
Other name:
BP102
Other name:
BP102 Biosimilar
Other name:
CT P16
Other name:
CT-P16
Other name:
CTP16
Other name:
Equidacent
Other name:
HD204
Other name:
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
Other name:
Mvasi
Other name:
MYL-1402O
Other name:
Onbevzi
Other name:
QL1101
Other name:
Recombinant Humanized Anti-VEGF Monoclonal Antibody
Other name:
rhuMab-VEGF
Other name:
SCT501
Other name:
SIBP 04
Other name:
SIBP-04
Other name:
SIBP04
Other name:
Vegzelma
Other name:
Zirabev
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Phase I (paclitaxel, tolinapant, bevacizumab)
Arm group label:
Phase II, Arm I (paclitaxel, bevacizumab)
Arm group label:
Phase II, Arm II (paclitaxel, tolinapant, bevacizumab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Phase I (paclitaxel, tolinapant, bevacizumab)
Arm group label:
Phase II, Arm I (paclitaxel, bevacizumab)
Arm group label:
Phase II, Arm II (paclitaxel, tolinapant, bevacizumab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Phase I (paclitaxel, tolinapant, bevacizumab)
Arm group label:
Phase II, Arm I (paclitaxel, bevacizumab)
Arm group label:
Phase II, Arm II (paclitaxel, tolinapant, bevacizumab)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
Given IV
Arm group label:
Phase I (paclitaxel, tolinapant, bevacizumab)
Arm group label:
Phase II, Arm I (paclitaxel, bevacizumab)
Arm group label:
Phase II, Arm II (paclitaxel, tolinapant, bevacizumab)
Other name:
Anzatax
Other name:
Asotax
Other name:
Bristaxol
Other name:
Praxel
Other name:
Taxol
Other name:
Taxol Konzentrat
Intervention type:
Drug
Intervention name:
Tolinapant
Description:
Given PO
Arm group label:
Phase I (paclitaxel, tolinapant, bevacizumab)
Arm group label:
Phase II, Arm II (paclitaxel, tolinapant, bevacizumab)
Other name:
ASTX 660
Other name:
ASTX660
Other name:
XIAP/cIAP1 Antagonist ASTX660
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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:
- 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
Exclusion Criteria:
- 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)
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
May 2, 2025
Completion date:
February 9, 2028
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06393751
