Bevacizumab and/or Niraparib in Patients With Recurrent Endometrial and/or Ovarian Cancer With ARID1A Mutation

NCT05523440 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: OU-SCC-ARID1A
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this research study is to test the proportion of tumor response to the combination treatment with niraparib and bevacizumab and see what effects (good and bad) this combination treatment has on patients with recurrent endometrial or ovarian cancer with ARID1A mutation.

Conditions

Recurrent Endometrial Carcinoma; Recurrent Ovarian Carcinoma; ARID1A Gene Mutation

Keywords

Niraparib; Bevacizumab; Endometrial Cancer; Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• Proportion of patients with objective response rate with recurrent endometrial cancer with mutated ARID1A

  To estimate the proportion of patients with objective tumor response (complete or partial), to the combination treatment of niraparib and bevacizumab and to monotherapy niraparib.

  3 years

• Proportion of patients with objective response rate with recurrent ovarian cancer with mutated ARID1A

  To estimate the proportion of patients with objective tumor response (complete or partial), to the combination treatment of niraparib and bevacizumab and to monotherapy niraparib.

  3 years

Secondary Outcomes (3)

• Incidence of Adverse Events

  3 years

• Duration of Response

  3 years

• Progression Free Survival

  3 years

Study Arms (2)

Arm 1: Niraparib

ACTIVE COMPARATOR

Niraparib (200mg or 300 mg based on body weight and blood platelet count), oral, once daily.

Drug: Niraparib

Arm 2: Niraparib and Bevacizumab

EXPERIMENTAL

Niraparib (200mg or 300 mg based on body weight and blood platelet count), oral, once daily. Bevacizumab (15 mg/kg, IV on day 1 of each cycle).

Drug: Bevacizumab; Drug: Niraparib

Interventions

Bevacizumab DRUG

Bevacizumab infusion.

Also known as: Avastin

Arm 2: Niraparib and Bevacizumab

Niraparib DRUG

Niraparib oral capsule.

Also known as: Zejula

Arm 1: Niraparib; Arm 2: Niraparib and Bevacizumab

Eligibility Criteria

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

You may qualify if:

• Female subjects ≥ 18 years of age.
• Histologically confirmed progressive or recurrent endometrial cancer or ovarian cancer with previously identified ARID1A tumor mutations.
• a. Any ARID1A mutation is eligible and any CLIA Next generation sequencing test is allowable for eligibility.
• Archival tumor tissue specimen available. Histological tissue specimen (tissue block or 8-10 unstained slides) must be available (specimen can be the sample at diagnosis or taken at relapse). Otherwise, patient must agree to have tumor biopsy to obtain sufficient tissue for histological assessment. If unable to be safely biopsied and patient desires enrollment, may be enrolled per MM discretion.
• A subset of patients (15 ovarian samples and 15 endometrial samples) should agree to have optional tumor biopsy for translational studies assessment. If unable to be safely biopsied and patient desires enrollment, may be enrolled per medical monitor discretion. Tissue collection for the optional translational biopsies will continue until a total of 30 viable samples have been collected (15 endometrial and 15 ovarian). Patient agrees to have blood draw at pre-treatment and post-treatment (end of study) for translational studies assessment.
• Patients who have progressed after ≥1 prior platinum containing 5.2 regimen.
• Patient must agree to have blood draw at pre- and post-treatment for correlative studies.
• Measurable disease by RECIST criteria v1.1.
• ECOG performance status 0 or 1.
• Patients should have no major existing co-morbidities or medical conditions that will preclude therapy in the view of the principal investigator.
• Life expectancy \> 12 weeks.
• Adequate bone marrow, hepatic and renal function as defined by the following values within 14 days prior to starting treatment:
• Hemoglobin \>9 g/dL Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
• Platelet count ≥ 100 x 109/L with no platelet transfusion in the past 28 days.
• Creatinine clearance ≥50 mL/min (estimated using Cockcroft-Gault equation).

You may not qualify if:

• Patients with localized advanced disease without other measurable lesion and could be treated with curative intent.
• Other malignancy within the last 5 years that would be expected to impact on overall survival. Prior malignancy with no expected impact on overall survival are allowed.
• Patients with myelodysplastic syndrome/acute myeloid leukemia history or with features suggestive of MDS/AML.
• Patients receiving radiotherapy within 2 weeks prior to study treatment.
• Major surgery within 4 weeks of starting study treatment.
• Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
• Any previous treatment with PARP inhibitor, including niraparib.
• Clinically significant (e.g. active) cardiovascular disease, uncontrolled high blood pressure. Uncontrolled high blood pressure defined as values ≥160/100 or symptomatic, refer to CTCAE.
• Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub- Arachnoids Hemorrhage (SAH) within 6 months prior to study treatment.
• Patients with increased risk of bleeding or history or evidence of hemorrhagic disorders within 6 months prior to study treatment.
• Resting ECG with QTc \> 470 msec on 2 or more time points within a 24-hour period or family history of long QT syndrome
• Persistent toxicities (Common Terminology Criteria for Adverse Event (CTCAE) \> grade 2) caused by previous cancer therapy, excluding alopecia.
• Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
• Pregnant or lactating woman.

Sponsors & Collaborators

• University of Oklahoma: lead
• GlaxoSmithKline: collaborator
• University of Virginia: collaborator

Study Sites (2)

University of Oklahoma Health Sciences Center, Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22903, United States

Location

Related Publications (1)

• Gaitskell K, Rogozinska E, Platt S, Chen Y, Abd El Aziz M, Tattersall A, Morrison J. Angiogenesis inhibitors for the treatment of epithelial ovarian cancer. Cochrane Database Syst Rev. 2023 Apr 18;4(4):CD007930. doi: 10.1002/14651858.CD007930.pub3.

  PMID: 37185961 DERIVED

MeSH Terms

Conditions

Endometrial Neoplasms; Ovarian Neoplasms

Interventions

Bevacizumab; niraparib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lauren Dockery, MD

  Stephenson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2022
• First Posted: August 31, 2022
• Study Start: February 15, 2023
• Primary Completion: January 8, 2025
• Study Completion: January 8, 2025
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)