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Combination Niraparib and Dostarlimab Therapy for Recurrent or Persistent Uterine Serous Carcinoma

Primary Purpose

Recurrent Endometrial Serous Adenocarcinoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Biospecimen Collection
Computed Tomography
Dostarlimab
Magnetic Resonance Imaging
Niraparib
Sponsored by
Casey Cosgrove
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Endometrial Serous Adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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 immunotherapy including single-agent pembrolizumab, other immunotherapy agents, or combination pembrolizumab and lenvatinib therapy will be allowed only if the patient did not progress or have an immune associated toxicity leading to discontinuation 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 Platelets >= 100,000/uL Hemoglobin >= 9 g/dL Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance >= 60 mL/min using the Cockcroft-Gault equation Total bilirubin =< 1.5 x ULN (=< 2.0 in patients with known Gilberts syndrome) OR direct bilirubin =< 1 x ULN Aspartate aminotransferase and alanine aminotransferase =< 2.5 x ULN unless liver metastases are present, in which case they must be =< 5 x ULN International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy and dose < 10 mg of prednisone or equivalent Participant must be able to take oral medications Participant must agree to not donate blood during the study or for 120 days after the last dose of study treatment If of childbearing potential, has a negative serum pregnancy test within 7 days prior to taking study medication and agrees to abstain from activities that could result in pregnancy from enrollment through 180 days (6 months) after the last dose of study treatment or be of non-childbearing potential. Non childbearing potential is defined as follows (by other than medical reasons): >= 45 years of age and has not had menses for > 1 year Patients who have been amenorrhoeic for < 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation Surgically sterile as defined as post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient Participant must agree to not breastfeed during the study or for 120 days after the last dose of study treatment Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent Must have recovered to =< grade 1 from all toxicities related to prior treatment that are deemed clinically relevant in the opinion of the investigator at time of enrollment 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 or PD1/PDL1 treatment 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 Participant has had any known grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) Participant must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled hypertension, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. Participants with hypertension but be well controlled before first dose of niraparib Participant must not have had diagnosis, detection, or treatment of another type of cancer =< 2 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated) Participant must not have a known history of brain or leptomeningeal metastases Participant has a diagnosis of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy Participant has a known history of human immunodeficiency virus (type 1 or 2 antibodies) Participant has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [qualitative] is detected) Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement hormone therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not an exclusion criterion Participant must not have a history of interstitial lung disease Participant is considered a poor medical risk that would interfere with cooperation with the requirements of the study Participant has received a live vaccine within 30 days of initiating protocol therapy Participant has a history of posterior reversible encephalopathy syndrome (PRES)

Sites / Locations

  • Ohio State University Comprehensive Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (dostarlimab, niraparib)

Arm Description

Patients receive dostarlimab IV and niraparib PO on study. Patients also undergo MRI/CT and collection of blood samples throughout the trial.

Outcomes

Primary Outcome Measures

Overall response rate
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 Outcome Measures

Clinical benefit rate
Clinical benefit rate (CR, PR, or stable disease [SD]) by RECIST v1.1 will be also estimated and reported with 95% confidence interval (exact).
Progression free survival (PFS)
PFS will be analyzed by Kaplan-Meier (KM) methods, and point estimates and 2-sided 95% confidence intervals for PFS will be reported for selected times such as 3, 6 and 12 months from treatment start using Greenwood's variance and the log-log transform method. Median PFS time, if attained, will also be reported.
Overall survival (OS)
OS will be analyzed by KM methods. Median OS time, if attained, will also be reported.
Duration of response (DoR)
DoR will be evaluated by restricted mean DoR.
Incidence of adverse events (AEs)
Toxicity will be summarized by reporting the number of patients treated, the number who experience treatment related toxicity, serious adverse events and grade 3 or higher AE, the number of patients who discontinue therapy, and the reasons for discontinuation. Comprehensive safety data on all grade 3 and 4 toxicities will be tabulated by type, grade, and duration.

Full Information

First Posted
May 12, 2023
Last Updated
October 9, 2023
Sponsor
Casey Cosgrove
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1. Study Identification

Unique Protocol Identification Number
NCT05870761
Brief Title
Combination Niraparib and Dostarlimab Therapy for Recurrent or Persistent Uterine Serous Carcinoma
Official Title
Phase II Trial of Combination Niraparib and Dostarlimab Therapy for Recurrent or Persistent Uterine Serous Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 30, 2023 (Anticipated)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Casey Cosgrove

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Endometrial Serous Adenocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (dostarlimab, niraparib)
Arm Type
Experimental
Arm Description
Patients receive dostarlimab IV and niraparib PO on study. Patients also undergo MRI/CT and collection of blood samples throughout the trial.
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo collection of blood samples
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography
Intervention Description
Undergo MRI/CT
Intervention Type
Biological
Intervention Name(s)
Dostarlimab
Other Intervention Name(s)
ANB011, Dostarlimab-gxly, Immunoglobulin G4, Anti-programmed Cell Death Protein 1 (PDCD1) (Humanized Clone ABT1 Gamma4-chain), Disulfide with Humanized Clone ABT1 Kappa-chain, Dimer, Jemperli, TSR 042, TSR-042, TSR042
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Magnetic Resonance Imaging
Other Intervention Name(s)
Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging
Intervention Description
Undergo MRI/CT
Intervention Type
Drug
Intervention Name(s)
Niraparib
Other Intervention Name(s)
MK-4827, MK4827
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Overall response rate
Description
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).
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Clinical benefit rate
Description
Clinical benefit rate (CR, PR, or stable disease [SD]) by RECIST v1.1 will be also estimated and reported with 95% confidence interval (exact).
Time Frame
Up to 2 years
Title
Progression free survival (PFS)
Description
PFS will be analyzed by Kaplan-Meier (KM) methods, and point estimates and 2-sided 95% confidence intervals for PFS will be reported for selected times such as 3, 6 and 12 months from treatment start using Greenwood's variance and the log-log transform method. Median PFS time, if attained, will also be reported.
Time Frame
From the date of study entry until disease progression or death (whichever occurs first), assessed up to 2 years
Title
Overall survival (OS)
Description
OS will be analyzed by KM methods. Median OS time, if attained, will also be reported.
Time Frame
Up to 2 years
Title
Duration of response (DoR)
Description
DoR will be evaluated by restricted mean DoR.
Time Frame
Up to 2 years
Title
Incidence of adverse events (AEs)
Description
Toxicity will be summarized by reporting the number of patients treated, the number who experience treatment related toxicity, serious adverse events and grade 3 or higher AE, the number of patients who discontinue therapy, and the reasons for discontinuation. Comprehensive safety data on all grade 3 and 4 toxicities will be tabulated by type, grade, and duration.
Time Frame
Up to 90 days

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 immunotherapy including single-agent pembrolizumab, other immunotherapy agents, or combination pembrolizumab and lenvatinib therapy will be allowed only if the patient did not progress or have an immune associated toxicity leading to discontinuation 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 Platelets >= 100,000/uL Hemoglobin >= 9 g/dL Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance >= 60 mL/min using the Cockcroft-Gault equation Total bilirubin =< 1.5 x ULN (=< 2.0 in patients with known Gilberts syndrome) OR direct bilirubin =< 1 x ULN Aspartate aminotransferase and alanine aminotransferase =< 2.5 x ULN unless liver metastases are present, in which case they must be =< 5 x ULN International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin (PTT) is within therapeutic range of intended use of anticoagulants Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy and dose < 10 mg of prednisone or equivalent Participant must be able to take oral medications Participant must agree to not donate blood during the study or for 120 days after the last dose of study treatment If of childbearing potential, has a negative serum pregnancy test within 7 days prior to taking study medication and agrees to abstain from activities that could result in pregnancy from enrollment through 180 days (6 months) after the last dose of study treatment or be of non-childbearing potential. Non childbearing potential is defined as follows (by other than medical reasons): >= 45 years of age and has not had menses for > 1 year Patients who have been amenorrhoeic for < 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation Surgically sterile as defined as post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient Participant must agree to not breastfeed during the study or for 120 days after the last dose of study treatment Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent Must have recovered to =< grade 1 from all toxicities related to prior treatment that are deemed clinically relevant in the opinion of the investigator at time of enrollment 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 or PD1/PDL1 treatment 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 Participant has had any known grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) Participant must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled hypertension, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. Participants with hypertension but be well controlled before first dose of niraparib Participant must not have had diagnosis, detection, or treatment of another type of cancer =< 2 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated) Participant must not have a known history of brain or leptomeningeal metastases Participant has a diagnosis of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy Participant has a known history of human immunodeficiency virus (type 1 or 2 antibodies) Participant has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [qualitative] is detected) Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement hormone therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not an exclusion criterion Participant must not have a history of interstitial lung disease Participant is considered a poor medical risk that would interfere with cooperation with the requirements of the study Participant has received a live vaccine within 30 days of initiating protocol therapy Participant has a history of posterior reversible encephalopathy syndrome (PRES)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
The Ohio State University Comprehensive Cancer Center
Phone
800-293-5066
Email
OSUCCCClinicaltrials@osumc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Casey Cosgrove, MD
Organizational Affiliation
Ohio State University Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Casey Cosgrove, MD
Phone
614-293-3873
Email
Casey.Cosgrove@osumc.edu
First Name & Middle Initial & Last Name & Degree
Casey Cosgrove, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://cancer.osu.edu
Description
The Jamesline

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Combination Niraparib and Dostarlimab Therapy for Recurrent or Persistent Uterine Serous Carcinoma

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