Recurrent Ovarian CarcinoSarcoma Anti-pd-1 Niraparib

NCT03651206 | Recruiting Phase 2 DMC

• 1 other identifier: ENGOT-en8
• Study Type: interventional
• Target: 138
• Locations: 3 countries
• Sites: 36

Brief Summary

Carcinosarcomas (CS) (malignant mixed Müllerian 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.

Conditions

Ovarian Carcinosarcoma; Endometrial Carcinosarcoma

Keywords

Malignant mixed Mullerian tumors; Metastatic ovarian carcinosarcoma; Recurrent ovarian carcinosarcoma; Metastatic endometrial carcinosarcoma; Recurrent endometrial carcinosarcoma; Niraparib; TSR-042 (Dostarlimab)

Outcome Measures

Primary Outcomes (2)

• Response Rate (RR) at 4 months

  RR is defined as the proportion of patients with a partial response or complete response 4 months after randomization

  4 months after the last patient included

• Overall survival (OS)

  OS is the time from the date of the randomization until death due to any cause

  1 year after the last patient included

Secondary Outcomes (6)

• Progression Free Survival (PFS)

  1 year after the last patient included

• Time To Subsequent Treatment (TTST)

  1 year after the last patient included

• Progression-Free Survival 2 (PFS2)

  1 year after the last patient included

• Objective Response Rate (ORR)

  1 year after the last patient included

• Adverse events

  1 year after the last patient included

Study Arms (3)

Arm A - Niraparib

EXPERIMENTAL

Niraparib, 200 mg or 300 mg, daily dose

Drug: Niraparib

Arm B - Niraparib + TSR-042 (Dostarlimab)

EXPERIMENTAL

Niraparib, 200 mg or 300 mg, daily dose TSR042, intravenous infusion on Day 1 of every 21-day cycle at 500 mg for the 4 first cycles, followed by 1,000 mg on Day 1 of every 42-day cycle thereafter

Combination Product: Niraparib + TSR-042 (Dostarlimab)

Arm C - Chemotherapy drugs

ACTIVE COMPARATOR

Chemotherapies (Standard of care) For Ovarian Cancer Patients Paclitaxel, 80 mg/m², Intravenous, Day 1, 8, 15 every 28 days Pegylated Liposomal Doxorubicin, 40 mg/m², Intravenous, every 28 days Topotecan, 4mg/m², Intravenous, Day 1, 8, 15 every 28 days For Endometrial Cancer Patients Doxorubicin, 60 mg/m², Intravenous, every 21 days Paclitaxel, 80 mg/m², Intravenous, Day 1, 8, 15 every 28 days Gemcitabine, 800 mg/m², Intravenous, Day 1, 8 every 21 days

Drug: Chemotherapy Drugs

Interventions

Niraparib DRUG

PARP Inhibitor

Arm A - Niraparib

Niraparib + TSR-042 (Dostarlimab) COMBINATION_PRODUCT

Combination of 2 drugs, a PARP Inhibitor and an Anti-PD-1

Arm B - Niraparib + TSR-042 (Dostarlimab)

Chemotherapy Drugs DRUG

Chemotherapies given in standard of care

Arm C - Chemotherapy drugs

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Progressive or recurrent uterine carcinosarcoma (Malignant Mixed Mullerian Tumor-MMMT).
• The primary diagnosis must be histologically confirmed by pathological expert review of the initial tumor or biopsy at relapse.
• Mandatory tumor samples: Availability of an archival FFPE tumor sample(s) from diagnosis, or if not available from relapse setting.
• Progressive disease as defined by RECIST 1.1.
• 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 radio-chemotherapy, 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 treatment; continuation of hormone replacement therapy is permitted.
• Patient must have ECOG Performance Status ≤1.
• 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:

You may not qualify if:

• 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 treatment initiation. Patient has had radiotherapy within 4 weeks prior to treatment initiation.
• Patients must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects
• Patient who has received more than 3 prior cytotoxic chemotherapies for management of uterine carcinosarcoma.
• Patient 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, NYHA 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)
• Patient 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 abnormalities. 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 \>10mg/day (prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy
• Participants with known HIV infection are allowed with the following requirements:
• Documented evidence of plasma HIV-1 RNA persistently \<50 copies/mL ≤3 months prior to AND at Screening. In the \>3 to 12 months prior to Screening, plasma HIV-1 RNA consistently \<50 c/mL required; if single increases ≥50 c/mL occurred, they cannot have been persistent nor associated with antiretroviral resistance per investigator assessment AND CD4 cell count \>350 cells/mm3 over past 12 months and at Screening (and no measurement ≤350 cells/mm3 during that time period) AND Must be on an uninterrupted combination antiretroviral therapy regimen for at least 3 months prior to Screening, with combination antiretroviral therapy regimen consistent with locally recommended guidelines Participants with history of CDC Stage 3 AIDS-defining disease (CDC, 2014; also known as acquired immunodeficiency syndrome - defining disease) are allowed if AIDS-defining disease has been treated and cured or is stable for ≥3 months prior to study entry. Cutaneous Kaposi's sarcoma not requiring systemic therapy is allowed.
• No history of HIV-associated non-Hodgkin lymphoma ≤5 years prior to study entry.

Sponsors & Collaborators

• ARCAGY/ GINECO GROUP: lead
• Tesaro, Inc.: collaborator

Study Sites (36)

ICO Paul Papin

Angers, 49055, France

RECRUITING

CHRU Jean Minjoz

Besançon, 25000, France

ACTIVE NOT RECRUITING

Centre Régional de Lutte contre le cancer - Institut Bergonié

Bordeaux, 33000, France

RECRUITING

CHU de BREST - Hôpital Cavale Blanche

Brest, 29200, France

NOT YET RECRUITING

Centre François Baclesse

Caen, 14000, France

RECRUITING

Centre Jean Perrin

Clermont-Ferrand, 63000, France

RECRUITING

Centre Georges François Leclerc

Dijon, 21079, France

NOT YET RECRUITING

Centre Oscar Lambret

Lille, 59000, France

RECRUITING

CHU de Limoges - Hôpital Dupuytren

Limoges, 87042, France

NOT YET RECRUITING

Centre Léon Bérard

Lyon, 69001, France

RECRUITING

Institut Paoli Calmettes

Marseille, 13000, France

RECRUITING

Hôpital Privé du Confluent S.A.S.

Nantes, 44000, France

ACTIVE NOT RECRUITING

Centre Hospitalier Universitaire de Nîmes, Institut de Cancérologie du GARD

Nîmes, 30900, France

NOT YET RECRUITING

Groupe Hospitalier des Diaconesses Croix Saint-Simon

Paris, 75020, France

RECRUITING

Institut Curie

Paris, 76016, France

RECRUITING

Hopital Milétrie - Centre Hospitalier Universitaire Poitiers

Poitiers, 86000, France

RECRUITING

Centre Eugène Marquis

Rennes, 35000, France

RECRUITING

ICO - Centre René Gauducheau

Saint-Herblain, 44800, France

RECRUITING

CHU Saint-Etienne - Pôle de Cancérologie

Saint-Priest-en-Jarez, 42271, France

NOT YET RECRUITING

ICANS

Strasbourg, 67200, France

COMPLETED

Hôpitaux Universitaires de Strasbourg

Strasbourg, France

RECRUITING

IUCT Oncopole - Institut Claudius Régaud

Toulouse, 31000, France

RECRUITING

ICL - Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54519, France

NOT YET RECRUITING

Institut Gustave Roussy

Villejuif, 94800, France

RECRUITING

Azienda Ospedaliero-Universitaria di Bologna IRCCS Istituto di Ricerca e di Cura a Carattere Scientifico

Bologna, 40138, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliera Per L'Emergenza Cannizzaro

Catania, 95126, Italy

ACTIVE NOT RECRUITING

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.

Meldola, 47014, Italy

ACTIVE NOT RECRUITING

Ospedale San Raffaele S.r.l.

Milan, 20132, Italy

ACTIVE NOT RECRUITING

Humanitas Mirasole S.p.A.

Milan, 20159, Italy

ACTIVE NOT RECRUITING

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Naples, 80131, Italy

ACTIVE NOT RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliera Ordine Mauriziano Di Torino

Torino, 10128, Italy

ACTIVE NOT RECRUITING

Hospital Universitario Ramon Y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Universitario 12 De Octubre

Madrid, 28041, Spain

ACTIVE NOT RECRUITING

Hospital Virgen de la Arrixaca

Murcia, 30120, Spain

ACTIVE NOT RECRUITING

Hospital Clinico Universitario De Valencia

Valencia, 46010, Spain

ACTIVE NOT RECRUITING

MeSH Terms

Interventions

niraparib; dostarlimab; Antineoplastic Agents

Intervention Hierarchy (Ancestors)

Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Central Study Contacts

Isabelle RAY-COQUARD, Professor

CONTACT

+33184852020; apailhe@arcagy.org

Bénédicte VOTAN

CONTACT

+33184852020; apailhe@arcagy.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Step 1 : Arm A - Niraparib Arm B - Niraparib plus TSR-042 Arm C - Chemotherapy drugs Peak the winner between the Arm A or the arm B Step 2 : Single arm - Niraparib plus TSR-042

Study Record Dates

• First Submitted: August 20, 2018
• First Posted: August 29, 2018
• Study Start: July 15, 2020
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): March 1, 2029
• Last Updated: June 1, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (8); ES (4); FR (24)