Trial on NIraparib-TSR-042 (Dostarlimab) vs Physician's Choice CHEmotherapy in Recurrent, Ovarian, Fallopian Tube or Primary Peritoneal Cancer Patients Not Candidate for Platinum Retreatment

NCT04679064 | Unknown Phase 3

• 1 other identifier: 3392
• Study Type: interventional
• Target: 427
• Locations: 1 country
• Sites: 8

Brief Summary

Randomized phase 3 trial evaluating niraparib plus dostarlimab vs chemotherapy at physician's choice in the treatment of recurrent ovarian, fallopian tube or primary peritoneal cancer patients for which platinum is not an option

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  The length of time from tfrom the date of randomization to the date of death by any cause

  4 years

Secondary Outcomes (13)

• Progression free survival

  4 years

• Time to first subsequent therapy

  4 years

• Response rate

  4 years

• Number and type of adverse events

  4 years

• Patient-reported outcomes for physical well-being

  4 years

Study Arms (2)

Phisician's choice of standard chemotherapy

ACTIVE COMPARATOR

Chemotherapy at physician's choice between Pegylated Liposomal Doxorubicin 40 mg/mq iv q 28 Weekly Paclitaxel 80 mg/mq d 1,8,15 q 28 Gemcitabine 1000 mg/mq d 1,8,15 q 28 Topotecan 1.25 mg/mq day 1-5 q 21 +/- Bevacizumab at defined scehedule

Drug: Pegylated liposomal doxorubicin; Drug: Paclitaxel; Drug: Gemcitabine; Drug: Topotecan; Drug: Bevacizumab

Niraparib+Dostarlimab

EXPERIMENTAL

Dostarlimab 500 mg q 3W for the fist 4 cycles, 1000 mg q 6W thereafter + Niraparib 300 mg or 200 mg if platelet count \<150,000 /μL and/or body weight \<77kg QD po q 28

Drug: Niraparib; Drug: Dostarlimab

Interventions

Niraparib DRUG

PARP-inihibitor

Also known as: Zejula

Niraparib+Dostarlimab

Dostarlimab DRUG

PD-1 inihibitor

Also known as: TSR-042

Niraparib+Dostarlimab

Pegylated liposomal doxorubicin DRUG

Chemotherapy drug

Phisician's choice of standard chemotherapy

Paclitaxel DRUG

Chemotherapy drug

Phisician's choice of standard chemotherapy

Gemcitabine DRUG

Chemotherapy drug

Phisician's choice of standard chemotherapy

Topotecan DRUG

Chemotherapy drug

Phisician's choice of standard chemotherapy

Bevacizumab DRUG

Chemotherapy drug

Also known as: Avastin

Phisician's choice of standard chemotherapy

Eligibility Criteria

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

You may qualify if:

• Participant must have recurrent ovarian, Fallopian tube or primary peritoneal cancer not candidate for platinum retreatment; and in particular
• platinum resistant patients (platinum-free interval 1-6 months from last dose of platinum)
• patients for which platinum is contraindicated because of previous allergic reactions or residual toxicity (i.e nephrotoxicity or neurotoxicity)
• patients not able( in physician's opinion) to receive further platinum or not willing (in patients' opinion) to receive further platinum
• Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
• Participants must have measurable disease or evaluable based on RECIST 1.1 (patients with only CA 125 increase without evidence of disease are not included).
• Participant must be ≥ 18 years of age
• Participant must have adequate organ function
• Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy.
• Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
• Participants must agree to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1.
• Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen.
• Female participant 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.
• Participant must agree to not breastfeed during the study or for 180 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

You may not qualify if:

• Participant must not be simultaneously enrolled in any interventional clinical trial
• Participants have received \>2 previous CHT lines (previous treatment with parp inhibitors and/or anti check point inhibitors is allowed providing that at least 6 months from last treatment are intercurred)
• 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 shorter, prior initiating 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 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 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
• Participant must not have had diagnosis, detection, or treatment of another type of cancer ≤ 3 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 known, symptomatic brain or leptomeningeal metastases
• Patient experienced ≥ Grade 3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.
• 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.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead
• GlaxoSmithKline: collaborator

Study Sites (8)

Azienda Ospedaliera Spedali Civili

Brescia, Italy

RECRUITING

Istituto Tumori della Romagna IRST IRCCS

Meldola, Italy

RECRUITING

IEO-Istituto Europeo di Oncologia

Milan, Italy

RECRUITING

IRCCS Ospedale San Raffaele

Milan, Italy

RECRUITING

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Naples, Italy

RECRUITING

Nuovo Ospedale degli Infermi

Ponderano, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, 00168, Italy

RECRUITING

Istituti fisioterapici Ospitalieri - Istituto Tumori Regina Elena

Rome, Italy

RECRUITING

Related Publications (1)

• Musacchio L, Salutari V, Pignata S, Braicu E, Cibula D, Colombo N, Frenel JS, Zagouri F, Carbone V, Ghizzoni V, Giolitto S, Giudice E, Perri MT, Ricci C, Scambia G, Lorusso D. Randomized phase III trial on niraparib-TSR-042 (dostarlimab) versus physician's choice chemotherapy in recurrent ovarian, fallopian tube, or primary peritoneal cancer patients not candidate for platinum retreatment: NItCHE trial (MITO 33). Int J Gynecol Cancer. 2021 Oct;31(10):1369-1373. doi: 10.1136/ijgc-2021-002593.

  PMID: 34607820 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

niraparib; dostarlimab; liposomal doxorubicin; Paclitaxel; Gemcitabine; Topotecan; Bevacizumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Camptothecin; Alkaloids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Domenica Lorusso, MD

CONTACT

0630158545; domenica.lorusso@policlinicogemelli.it

Serena Giolitto, MSc

CONTACT

0630158545; serena.giolitto@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2020
• First Posted: December 22, 2020
• Study Start: December 1, 2020
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: August 27, 2021

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (8)