Using Genetic Profile to Determine the Treatment for Patients With Ovarian Cancer Who Previously Received a PARP-inhibitor

NCT05065021 | Unknown Phase 2 DMC

• 2 other identifiers: Re-VOLVE21-5915
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to see how useful it is to look at biomarkers in the blood and tumor tissue of participants with ovarian, fallopian tube or primary peritoneal cancer who have previously received treatment with a drug called a PARP inhibitor, and using the results to determine the best treatment for these participants. Biomarkers are molecules such as genes (molecules that contain instructions for the development and function of cells in the body) and proteins that may be used to see how well a body responds to certain treatments.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer; High Grade Serous Cancer; High Grade Endometrioid Cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of participants that achieve biomarker-guided treatment

  3 years

• Response rate percentage

  3 years

Secondary Outcomes (15)

• Overall response rate for Cohort A

  3 years

• Overall response rate for Cohort B

  3 years

• Overall response rate for initial cohort/Cohort C

  3 years

• Progression-free survival rate for initial cohort/Cohort C

  3 years

• Progression-free survival rate for initial cohort/Cohort A

  3 years

Study Arms (3)

Initial/Cohort C

EXPERIMENTAL

Niraparib by mouth (orally), once a day, every day. Bevacizumab, by vein (intravenously), once every 3 weeks for up to 1 year, then every 6 weeks.

Drug: Niraparib; Drug: Bevacizumab

Cohort A

EXPERIMENTAL

Niraparib by mouth (orally), once a day, every day. Bevacizumab, by vein (intravenously), once every 3 weeks for up to 1 year, then every 6 weeks. Dostarlimab, by vein (intravenously), once every 3 weeks for 4 doses, then every 6 weeks afterwards.

Drug: Niraparib; Drug: Dostarlimab; Drug: Bevacizumab

Cohort B

EXPERIMENTAL

Paclitaxel, by vein (intravenously), once a week. Bevacizumab, by vein (intravenously), once every 3 weeks for up to 1 year, then every 6 weeks. Dostarlimab, by vein (intravenously), once every 3 weeks for 4 doses, then every 6 weeks afterwards.

Drug: Dostarlimab; Drug: Bevacizumab; Drug: Paclitaxel

Interventions

Niraparib DRUG

Niraparib works by blocking poly(ADP-ribose) polymerases (PARP) 1 and PARP 2 from working. PARP 1 and PARP 2 are proteins that are involved in cell growth, cell survival, and cell death, including cancer cells. It is believed that blocking PARP1 and PARP 2 from working will slow or stop the growth of cancer cells.

Also known as: ZEJULA

Cohort A; Initial/Cohort C

Dostarlimab DRUG

Dostarlimab is a monoclonal antibody. Antibodies are proteins that are naturally found in the blood stream that fight infections. A monoclonal antibody is a special kind of antibody that is created in a laboratory that seeks out specific proteins in the body that may be involved in cancers to stop tumor growth. Dostarlimab attaches to PD-1 and inhibits the interaction of PD-L1 and PD-L2 with PD-1.

Cohort A; Cohort B

Bevacizumab DRUG

Bevacizumab is a chemotherapy drug commonly used for the treatment of various cancers.

Cohort A; Cohort B; Initial/Cohort C

Paclitaxel DRUG

Paclitaxel is a chemotherapy drug commonly used for the treatment of various cancers.

Cohort B

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Histologically confirmed ovarian, fallopian tube or primary peritoneal cancer, high grade serous or high grade endometrioid histology subtype.
• Patients must have relapsed disease, either platinum-sensitive, resistant or refractory, with no limit to number of lines of prior systemic therapy.
• Radiographically documented disease progression within 28 days of registration.
• Patient must have measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Progression on any prior Poly (ADP-ribose) polymerase (PARP) inhibitor therapy, with no limit to number of prior lines of PARP inhibitors.
• Patients must have adequate bone marrow, renal and hepatic function within 7 days of registration
• Left ventricular ejection fraction (LVEF) \> 50% by echocardiograms or multigated acquisition (MUGA) scan within 28 days of registration.
• Patients are willing to undergo tumor biopsy pre-treatment (tissue at the time of progression on PARP inhibitor therapy).
• Availability of archival tissue (prior to PARP inhibitor therapy) for analysis.
• Women of child-bearing potential must agree to use a highly effective contraceptive method for study-required period. A negative high sensitive urine or serum pregnancy test within 3 days prior to the initiation of therapy will be required for women of childbearing potential.
• Patient must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
• Patient must agree to not breastfeed during the study or for 30 days after the last dose of study treatment.

You may not qualify if:

• Treatment with an investigational (other than PARP inhibitor) drug within 30 days and treatment with PARP inhibitor within 14 days prior to the first dose of study medication.
• Major surgery within 4 weeks of registration or ongoing clinically significant post-surgical complications.
• Patients with current or are at high-risk of developing fistula, or any other gastrointestinal disorders likely to interfere with absorption of the study medication.
• Patients with current or history of bowel obstruction within the last 3 months.
• Untreated unstable brain or leptomeningeal metastases.
• Greater than +1 proteinuria on two consecutive dipsticks within 14 days of registration.
• Unresolved toxicity of \> grade 1 from previous anti-cancer therapy (including radiotherapy).
• History of poorly controlled hypertension or resting blood pressure \>140/90 mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy within 7 days of registration.
• Mean QTc \>470 msec in screening electrocardiograms within 7 days of registration or history of familial long QT syndrome.
• Any evidence of severe or uncontrolled diseases such as but not limited to unstable or uncompensated respiratory, cardiac, hepatic, renal disease or psychiatric illness/social situations that would limit compliance with study requirements.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab, paclitaxel, dostarlimab, or niraparib.
• Patients who have received prior weekly paclitaxel in the recurrent ovarian cancer setting.
• Patients who have received prior PD-1 inhibitor for ovarian cancer.
• Active autoimmune disease that has required systemic treatment in the past 2 years.
• History of interstitial lung disease.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

niraparib; dostarlimab; Bevacizumab; Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Stephanie Lheureux, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephanie Lheureux, M.D.

CONTACT

416-946-2818; stephanie.lheureux@uhn.ca

Study Design

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

Study Record Dates

• First Submitted: September 29, 2021
• First Posted: October 1, 2021
• Study Start: February 23, 2023
• Primary Completion: June 6, 2025
• Study Completion: June 6, 2025
• Last Updated: January 17, 2024

Record last verified: 2024-01

Locations

CA (1)