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Niraparib alone or with dostarlimab for recurrent ovarian or uterine carcinosarcoma

An International Multicentric Randomized Phase II Evaluating Dostarlimab in Combination With Niraparib Versus Niraparib Alone Compared to Chemotherapy in the Treatment of Metastatic or Recurrent Endometrial or Ovarian Carcinosarcoma After at Least One Line of Chemotherapy

Phase2; Phase3 Interventional Arcagy/ Gineco Group · NCT03651206

This trial tests whether the oral drug niraparib, alone or combined with the immunotherapy dostarlimab, helps people with recurrent or metastatic ovarian or uterine carcinosarcoma.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Enrollment138 (estimated)
Ages18 Years and up
SexFemale
SponsorArcagy/ Gineco Group Academic / other
Drugs / interventionschemotherapy, immunotherapy, radiation, prednisone, doxorubicin
Locations36 sites (Angers and 35 other locations)
Trial IDNCT03651206 on ClinicalTrials.gov

What this trial studies

This randomized phase 2/3 interventional trial enrolls adults with histologically confirmed recurrent or progressive ovarian or uterine carcinosarcoma after at least one platinum-containing regimen. Participants must provide recent tumor tissue for central pathology review and will receive niraparib alone, niraparib plus the anti‑PD‑1 antibody dostarlimab (TSR‑042), or chemotherapy according to protocol. The study compares tumor response, progression-free survival, and safety across treatment arms in patients with measurable disease by RECIST and progression within 12 months of their last chemotherapy. Centralized pathology and mandatory tumor sampling are used to ensure accurate diagnosis and translational analyses.

Who should consider this trial

Good fit: Adults with histologically confirmed recurrent or progressive ovarian or uterine carcinosarcoma who progressed within 12 months of their last chemotherapy, have received at least one prior platinum-containing regimen, and can provide a recent tumor sample are the intended participants.

Not a fit: Patients without recurrent/progressive disease by RECIST, those who cannot provide a recent tumor biopsy or archival tissue, or those with uncontrolled infection or significant organ dysfunction are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the treatments could increase response rates and extend progression-free survival compared with current chemotherapy options, potentially offering a targeted or immunotherapy-based alternative.

How similar studies have performed: PARP inhibitors and PD‑1 antibodies have shown activity in other gynecologic cancers, but their combination in carcinosarcoma is largely untested and remains an experimental approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Progressive or recurrent uterine or ovarian carcinosarcoma (Malignant Mixed Mullerian Tumor-MMMT).
2. The primary diagnosis must be histologically confirmed and central pathological review of the initial tumor or biopsy at relapse will be done.
3. Mandatory tumor samples: Availability of tumor sample(s) from a recently (not older than 3 months) obtained archival FFPE tumor tissue block or agreement for having a new tumor biopsy if lesion amenable, with ≥ 20% cellularity and tumoral surface ≥ 8 mm².
4. Progressive disease as defined by RECIST 1.1., within 12 months from last chemotherapy cycle.
5. Failure after ≥1 prior platinum containing regimen, which may have been given in the adjuvant setting.
6. Patient must have had 1 prior chemotherapeutic regimen for management of carcinosarcoma that may have included chemotherapy, chemotherapy and radiotherapy, and/or consolidation/maintenance therapy.
7. Patient must be free of active infection requiring antibiotics.
8. Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to beginning protocol chemotherapy; continuation of hormone replacement therapy is permitted.
9. Patient must have ECOG Performance Status ≤2.
10. Life expectancy of \> 2 months.
11. Adequate bone marrow function:

    * Platelet count greater than or equal to 100,000/mm3
    * Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3
    * Hemoglobin \> 9g/dL
12. Adequate hepatic and renal function:

    * Total bilirubin ≤1.5x Upper Limit of Normal (ULN) unless liver metastases are present, in which case they must be ≤3x ULN (≤2.0 in patients with known Gilberts syndrome OR direct bilirubin ≤ 1 x ULN)
    * Serum creatinine ≤1.5x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min using Cockcroft-Gault equation
    * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x ULN unless liver metastases are present, in which case they must be ≤5x ULN
    * Alkaline phosphatase \< 2.5 times ULN
    * Serum albumin \> 3 g/dL
13. International normalized ratio (INR) or prothrombin time (PT) ≤1.5× 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× ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
14. Patient must have normal BP or adequately treated and controlled hypertension (systolic BP≤140 mmHg and/or diastolic BP ≤90 mmHg)
15. Patient receiving corticosteroids may continue as long as their dose is stable and ≤10mg/day (prednisone equivalent) for at least 4 weeks prior to initiating protocol therapy.
16. Patient must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
17. Left ventricular ejection fraction (LVEF) \> Lower Limit of Normal (LLN) as assessed by either multigated acquisition (MUGA) scan or echocardiogram (ECHO), for patients planned to receive Anthracycline based therapy.
18. 18\. Patient has a negative urine or serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of nonchildbearing potential.

    * Non-childbearing potential is defined as follows:

      * ≥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
      * 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.
    * For women of childbearing potential: the patient must be willing to use a highly effective contraception measure throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. See Section 4.3. for a list of highly effective contraception methods. 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.
19. Patient must agree to not breastfeed during the study and for 180 days after the last dose of study treatment.
20. Patient able to take oral medications.
21. 21\. Female aged ≥18 years at time of signing ICF.
22. Patient must have signed an approved informed consent.
23. For France only: patient affiliated to, or a beneficiary of, a social security category.

Exclusion Criteria:

1. Not enrolled in any interventional clinical trial (except to biological trials that must be validated by the sponsor).
2. Prior treatment with niraparib or other PARPi therapy or PD1/PDL-1 inhibitors.
3. Patient has had investigational therapy, immunotherapy, chemotherapy or biological therapy administered within 4 weeks or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to randomization. Patient has had radiotherapy within 4 weeks prior to randomization.
4. Patient must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effect.
5. Previous treatment with the chemotherapy regimen selected as the control arm by the investigator.

   * Prior therapy with paclitaxel given on a three-weekly regimen is permitted for patients receiving weekly Paclitaxel.
   * Prior treatment with weekly paclitaxel is permitted where this has been used as part of first line therapy and it is greater than 6 months since the last dose of weekly paclitaxel.
   * Prior weekly paclitaxel for relapsed disease is not permitted.
6. Patients who have received more than 3 prior cytotoxic chemotherapies for management of uterine or ovarian carcinosarcoma.
7. Patients with persistent, clinically significant \> Grade 1 toxicity.
8. Patient has clinically significant cardiovascular disease (eg, significant cardiac conduction abnormalities, uncontrolled hypertension, myocardial infarction, uncontrolled cardiac arrhythmia or unstable angina \< 6 months to enrollment, NHYA grade 2 or greater congestive heart failure, serious cardiac arrhythmia requiring medication, Grade 2 or greater peripheral vascular disease, and history of cerebrovascular accident within 6 months)
9. Patients with any other severe concurrent disease, which may increase the risk associated with study participation or study drug administration and, in the judgment of the investigator, would make the patient inappropriate for entry into this study, including significant neurologic, psychiatric, infectious, hepatic, renal, or gastrointestinal diseases or laboratory abnormality. Examples include, but are not limited to, 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.
10. Symptoms or signs of gastrointestinal obstruction requiring parenteral nutrition or hydration or any other gastro-intestinal disorders or abnormalities, including difficulty swallowing, that would interfere with drug absorption.
11. Patient experienced ≥ Grade 3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities
12. Participant has had radiation therapy encompassing \>20% of the bone marrow within 2 weeks prior to Day 1 of protocol therapy, or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
13. Patient 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
14. Patient has a known history of human immunodeficiency virus (type 1 or 2 antibodies).
15. Patient 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).
16. Patient has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
17. Patient must not have a history of interstitial lung disease.
18. Patient has received a live vaccine within 14 days of initiating protocol therapy.
19. Patient must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy.
20. Patient 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.
21. Patient 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.
22. Patient must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
23. Symptomatic CNS metastasis or leptomeningeal carcinomatosis.
24. Patients with a history of other invasive malignancies (any evidence of other malignancy being present within the last 3 years) or with a concomitant invasive malignancy, with the exception of non-melanoma skin cancer; patients are also ineligible if their previous cancer treatment contraindicates this protocol therapy.
25. Known, hypersensitivity reactions or allergy to investigational drugs or their excipients that contraindicates the subject's participation.
26. Any psychological, familial, sociological or geographical consideration potentially hampering compliance with the study protocol and follow up schedule; those considerations should be discussed with the patient before registration in the trial.
27. Patients under psychiatric care and patients admitted to a health or social institution.
28. Patients deprived of their liberty by judicial or administrative decision.
29. Patients under a legal protection measure or unable to express their consent.

Where this trial is running

Angers and 35 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Ovarian CarcinosarcomaEndometrial CarcinosarcomaMalignant mixed Mullerian tumorsMetastatic ovarian carcinosarcomaRecurrent ovarian carcinosarcomaMetastatic endometrial carcinosarcomaRecurrent endometrial carcinosarcomaNiraparib
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.