Recurrent Ovarian CarcinoSarcoma Anti-pd-1 Niraparib

  • STATUS
    Recruiting
  • End date
    Jun 25, 2025
  • participants needed
    196
  • sponsor
    ARCAGY/ GINECO GROUP
Updated on 25 January 2021
Investigator
Isabelle RAY-COQUARD, Professor
Primary Contact
Centre Jean Perrin (1.6 mi away) Contact
+18 other location

Summary

Carcinosarcomas (CS) (malignant mixed Mllerian tumors) are highly aggressive and rare tumors with a worldwide annual incidence between 0.5-3.3 cases/100.000 women. Gynecological CS, i.e. ovarian CS (OCS) and uterine CS (UCS), have a 5-year overall survival (OS) < 10% and a poor prognosis. After initial treatment (surgery +/- adjuvant radiotherapies +/- chemotherapies (CT)), vast majority of patients relapsed and received diverse CT producing modest benefits, and nearly all patients will die. After first line CT including platinum salt, monotherapy (doxorubicin or paclitaxel) is frequently used for relapsed patients, but the response rate (RR) is <20%, progression-free survival (PFS) <4 months, and OS <1 year. In this unmet need situation, a better knowledge of these aggressive neoplasms is essential to propose new therapeutic options.

Details
Condition Ovarian Carcinosarcoma, Endometrial Carcinosarcoma
Treatment Niraparib, Niraparib + TSR-042 (Dostarlimab), Chemotherapy Drugs
Clinical Study IdentifierNCT03651206
SponsorARCAGY/ GINECO GROUP
Last Modified on25 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Progressive or recurrent uterine or ovarian carcinosarcoma (Malignant Mixed Mullerian Tumor-MMMT)
The primary diagnosis must be histologically confirmed and central pathological review of the initial tumor or biopsy at relapse will be done
Mandatory tumor sample: Availability of tumor sample 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
Progressive disease as defined by RECIST 1.1., within 12 months from last chemotherapy cycle
Failure after 1 prior platinum containing regimen, which may have been given in the adjuvant setting
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
Patient must be free of active infection requiring antibiotics
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
Patient must have ECOG Performance Status <2\
Life expectancy of > 2 months
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
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
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
Patient must have normal BP or adequately treated and controlled hypertension (systolic BP140 mmHg and/or diastolic BP 90 mmHg)
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
Patient must agree to not donate blood during the study or for 90 days after the last dose of study treatment
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
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
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 2 adequate barrier methods 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 acceptable birth control 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
Patient must agree to not breastfeed during the study and for 180 days after the last dose of study treatment
Patient able to take oral medications
21\. Female aged 18 years at time of signing ICF
Patient must have signed an approved informed consent
For France only: patient affiliated to, or a beneficiary of, a social security category

Exclusion Criteria

Not enrolled in any interventional clinical trial (except to biological trials that must be validated by the sponsor)
Prior treatment with niraparib or other PARPi therapy or PD1/PDL-1 inhibitors
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
Patient must not have had major surgery 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effect
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
Patients who have received more than 3 prior cytotoxic chemotherapies for management of uterine or ovarian carcinosarcoma
Patients with persistent, clinically significant > Grade 1 toxicity
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)
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
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
Patient experienced Grade 3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities
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
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
Patient has a known history of human immunodeficiency virus (type 1 or 2 antibodies)
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)
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
Patient must not have a history of interstitial lung disease
Patient has received a live vaccine within 14 days of initiating protocol therapy
Patient must not have received a transfusion (platelets or red blood cells) 4 weeks prior to initiating protocol therapy
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
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
Patient must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
Symptomatic CNS metastasis or leptomeningeal carcinomatosis
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
Known, uncontrolled hypersensitivity reactions or allergy to investigational drugs or their excipients that contraindicates the subject's participation
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
Patients under psychiatric care and patients admitted to a health or social institution
Patients deprived of their liberty by judicial or administrative decision
Patients under a legal protection measure or unable to express their consent
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