Trial Title:
Combination Niraparib and Dostarlimab Therapy for Recurrent or Persistent Uterine Serous Carcinoma
NCT ID:
NCT05870761
Condition:
Recurrent Endometrial Serous Adenocarcinoma
Conditions: Official terms:
Cystadenocarcinoma, Serous
Recurrence
Niraparib
Dostarlimab
Immunoglobulins
Immunoglobulin G
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Treatment (dostarlimab, niraparib)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo MRI/CT
Arm group label:
Treatment (dostarlimab, niraparib)
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:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Biological
Intervention name:
Dostarlimab
Description:
Given IV
Arm group label:
Treatment (dostarlimab, niraparib)
Other name:
ANB011
Other name:
Dostarlimab-gxly
Other name:
Immunoglobulin G4, Anti-programmed Cell Death Protein 1 (PDCD1) (Humanized Clone ABT1 Gamma4-chain), Disulfide with Humanized Clone ABT1 Kappa-chain, Dimer
Other name:
Jemperli
Other name:
TSR 042
Other name:
TSR-042
Other name:
TSR042
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI/CT
Arm group label:
Treatment (dostarlimab, niraparib)
Other name:
Magnetic Resonance
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:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Intervention type:
Drug
Intervention name:
Niraparib
Description:
Given PO
Arm group label:
Treatment (dostarlimab, niraparib)
Other name:
MK-4827
Other name:
MK4827
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.
Criteria for 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
- 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
- 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)
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Casey Cosgrove, MD
Phone:
614-293-3873
Email:
Casey.Cosgrove@osumc.edu
Investigator:
Last name:
Casey Cosgrove, MD
Email:
Principal Investigator
Start date:
October 17, 2023
Completion date:
December 31, 2024
Lead sponsor:
Agency:
Casey Cosgrove
Agency class:
Other
Source:
Ohio State University Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05870761
http://cancer.osu.edu
