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

NCT ID: NCT04679064

Last Updated: 2021-08-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

427 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-01

Study Completion Date

2025-01-01

Brief Summary

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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

Detailed Description

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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.

The patients must have received no more than 2 previous chemotherapy lines. Stratification factors will include HRD status, previous treatment with parp and anti PD-1/PDL-1 inhibitors, Bevacizumab treatment and PDL1 expression.

Patients will continue to receive niraparib until disease progression (determined using RECIST v.1.1 criteria and clinical criteria), unacceptable toxicity, death, withdrawal of consent, or lost to follow-up, whichever comes first. Patients will continue to receive dostarlimab for a maximum of 2 years, or until disease progression (determined using RECIST v1.1 criteria and clinical criteria), unacceptable toxicity, death, withdrawal of consent, lost to follow-up, whichever may come first. Dose interruption and/or reduction may be implemented at any time for any grade toxicity considered intolerable by the patient.

Conditions

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Ovarian Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phisician's choice of standard chemotherapy

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

Group Type ACTIVE_COMPARATOR

Pegylated liposomal doxorubicin

Intervention Type DRUG

Chemotherapy drug

Paclitaxel

Intervention Type DRUG

Chemotherapy drug

Gemcitabine

Intervention Type DRUG

Chemotherapy drug

Topotecan

Intervention Type DRUG

Chemotherapy drug

Bevacizumab

Intervention Type DRUG

Chemotherapy drug

Niraparib+Dostarlimab

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

Group Type EXPERIMENTAL

Niraparib

Intervention Type DRUG

PARP-inihibitor

Dostarlimab

Intervention Type DRUG

PD-1 inihibitor

Interventions

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Niraparib

PARP-inihibitor

Intervention Type DRUG

Dostarlimab

PD-1 inihibitor

Intervention Type DRUG

Pegylated liposomal doxorubicin

Chemotherapy drug

Intervention Type DRUG

Paclitaxel

Chemotherapy drug

Intervention Type DRUG

Gemcitabine

Chemotherapy drug

Intervention Type DRUG

Topotecan

Chemotherapy drug

Intervention Type DRUG

Bevacizumab

Chemotherapy drug

Intervention Type DRUG

Other Intervention Names

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Zejula TSR-042 Avastin

Eligibility Criteria

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Inclusion Criteria

1. 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
2. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
3. 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).
4. Participant must be ≥ 18 years of age
5. Participant must have adequate organ function
6. Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy.
7. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment.
8. 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.
9. 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.
10. Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment.
11. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent

Exclusion Criteria

1. Participant must not be simultaneously enrolled in any interventional clinical trial
2. 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)
3. Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
4. 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.
5. 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.
6. Participant must not have a known hypersensitivity to niraparib and dostarlimab components or excipients.
7. Participant must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy.
8. 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.
9. 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.
10. Participant must not have any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
11. 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
12. 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)
13. Participant must not have known, symptomatic brain or leptomeningeal metastases
14. Patient experienced ≥ Grade 3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.
15. 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.
16. Participant has a known history of human immunodeficiency virus (type 1 or 2 antibodies).
17. 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).
18. Participant 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.
19. Participant must not have a history of interstitial lung disease.
20. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
21. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines are live attenuated vaccines, and are not allowed.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Azienda Ospedaliera Spedali Civili

Brescia, , Italy

Site Status RECRUITING

Istituto Tumori della Romagna IRST IRCCS

Meldola, , Italy

Site Status RECRUITING

IEO-Istituto Europeo di Oncologia

Milan, , Italy

Site Status RECRUITING

IRCCS Ospedale San Raffaele

Milan, , Italy

Site Status RECRUITING

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Naples, , Italy

Site Status RECRUITING

Nuovo Ospedale degli Infermi

Ponderano, , Italy

Site Status RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, , Italy

Site Status RECRUITING

Istituti fisioterapici Ospitalieri - Istituto Tumori Regina Elena

Rome, , Italy

Site Status RECRUITING

Countries

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Italy

Central Contacts

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Domenica Lorusso, MD

Role: CONTACT

0630158545 ext. 0630158545

Serena Giolitto, MSc

Role: CONTACT

0630158545 ext. 0630158545

Facility Contacts

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Domenica Lorusso, MD

Role: primary

0630158545 ext. 0630158545

Serena Giolitto, MSc

Role: backup

0630158545 ext. 0630158545

References

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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.

Reference Type DERIVED
PMID: 34607820 (View on PubMed)

Other Identifiers

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3392

Identifier Type: -

Identifier Source: org_study_id

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