Phase II Trial of Combination Niraparib and Dostarlimab Therapy for Recurrent or Persistent Uterine Serous Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Biospecimen Collection
- Conditions
- Recurrent Endometrial Serous Adenocarcinoma
- Sponsor
- Casey Cosgrove
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Overall response rate
- Status
- Active, not recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
This phase II trial tests how well niraparib and dostarlimab work in treating patients with uterine serous carcinoma that has come back (after a period of improvement) (recurrent) and remains despite treatment (persistent). Niraparib belongs to a class of drugs called PARP inhibitors that prevent cancer cells from growing. Dostarlimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Dostarlimab belongs to a class of drugs called PD-1 inhibitors that uses the patient's own immune system to treat cancer (immuno-therapy). Giving niraparib and dostarlimab may work better in treating patients with uterine serous carcinoma.
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate the efficacy, as measured by confirmed overall response rate (ORR) (partial and complete response, PR/CR) per Response Evaluation Criteria in Solid Tumors (RECIST version \[v\]1.1) based on investigator assessment of the combination niraparib and dostarlimab in patients with recurrent or persistent uterine serous carcinoma (USC). SECONDARY OBJECTIVES: I. Estimate the progression-free survival (PFS). II. Estimate clinical benefit rate (CBR), defined as the percentage of patients who have achieved complete response (CR), partial response (PR) or stable disease (SD). III. Evaluate the safety and tolerability of niraparib and dostarlimab combination. TRANSLATIONAL OBJECTIVE: I. Biomarker evaluation to predict response. OUTLINE: Patients receive dostarlimab intravenously (IV) and niraparib orally (PO) on study. Patients also undergo magnetic resonance imaging (MRI)/computed tomography (CT) and collection of blood samples throughout the trial. After completion of study treatment, patients are followed up every 6 months for 2 years and then annually thereafter.
Investigators
Casey Cosgrove
Principal Investigator
Ohio State University Comprehensive Cancer Center
Eligibility Criteria
Inclusion Criteria
- •Participant must have recurrent or persistent uterine serous carcinoma based on previous biopsy or surgery, and have previously received at least carboplatin/paclitaxel. Mixed and carcinosarcoma histology cases will be eligible if there is a serous component in the tumor
- •Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1
- •Participant must be \>= 18 years of age
- •Patient has archival tumor tissue available or a fresh biopsy of recurrent or persistent tumor must be obtained prior to study treatment initiation
- •Patient must have measurable disease by RECIST
- •No more than three prior chemotherapy regimens (does not include chemoradiation) are permitted. One of the previous lines of treatment must include carboplatin and paclitaxel
- •Prior PD1/PDL1 inhibitors (including single-agent pembrolizumab, other immunotherapy agents, or combination pembrolizumab and lenvatinib) therapy will be allowed if the patient did not have immune associated toxicity leading to discontinuation.
- •Patients who have progressed on prior PD1/PDL1 inhibitors may be allowed to participate if the study PI and treating physician deem it to be within the patient's best interest.
- •Prior chemoradiation therapy for adjuvant treatment or pelvic recurrence is permitted. Chemotherapy in this setting, is not counted as prior line of chemotherapy
- •Absolute neutrophil count \>= 1,500/uL
Exclusion Criteria
- •Participant must not be simultaneously enrolled in any interventional clinical trial
- •Participant must not have had major surgery =\< 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects
- •Participant must not have received investigational therapy =\< 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior initiating protocol therapy
- •Participant's last treatment with platinum based chemotherapy was =\< 4 weeks from initiation of protocol therapy
- •Participant has had radiation therapy encompassing \> 20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to day 1 of protocol therapy
- •Participant must not have a known hypersensitivity to niraparib and dostarlimab components or excipients
- •Participant must not have previously progressed on PARP inhibitor
- •Participant experienced \>= grade 3 immune-related adverse event (AE) with prior immunotherapy, with the exception of non-clinically significant lab abnormalities
- •Participant must not have received a transfusion (platelets or red blood cells) =\< 4 weeks prior to initiating protocol therapy
- •Participant must not have received colony-stimulating factors (eg, granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy
Arms & Interventions
Treatment (dostarlimab, niraparib)
Patients receive dostarlimab IV and niraparib PO on study. Patients also undergo MRI/CT and collection of blood samples throughout the trial.
Intervention: Biospecimen Collection
Treatment (dostarlimab, niraparib)
Patients receive dostarlimab IV and niraparib PO on study. Patients also undergo MRI/CT and collection of blood samples throughout the trial.
Intervention: Computed Tomography
Treatment (dostarlimab, niraparib)
Patients receive dostarlimab IV and niraparib PO on study. Patients also undergo MRI/CT and collection of blood samples throughout the trial.
Intervention: Dostarlimab
Treatment (dostarlimab, niraparib)
Patients receive dostarlimab IV and niraparib PO on study. Patients also undergo MRI/CT and collection of blood samples throughout the trial.
Intervention: Magnetic Resonance Imaging
Treatment (dostarlimab, niraparib)
Patients receive dostarlimab IV and niraparib PO on study. Patients also undergo MRI/CT and collection of blood samples throughout the trial.
Intervention: Niraparib
Outcomes
Primary Outcomes
Overall response rate
Time Frame: Up to 2 years
Defined as the percentage of patients with complete response (CR), or partial response (PR), as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version (v.) 1.1 criteria using investigator's review. Will be estimated and reported with 95% confidence intervals (exact).
Secondary Outcomes
- Clinical benefit rate(Up to 2 years)
- Progression free survival (PFS)(From the date of study entry until disease progression or death (whichever occurs first), assessed up to 2 years)
- Overall survival (OS)(Up to 2 years)
- Duration of response (DoR)(Up to 2 years)
- Incidence of adverse events (AEs)(Up to 90 days)