Randomized phase III trial on NIraparib-Dostarlimab vs physician’s choice CHEmotherapy in recurrent, ovarian, fallopian tube or primary peritoneal cancer patients not candidate for platinum retreatment: NItCHE trial (MITO33)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Dec 2020 → ongoing

Decision date (initial)

2024-11-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516649-38-00

EudraCT number

2020-000146-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess overall survival (OS), defined as the time from randomization to the date of death by any cause

Conditions and MedDRA coding

Recurrent ovarian, fallopian tube or primary peritoneal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. a. 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 the first platinum treatment) - patients for which platinum is contraindicated because of previous allergic reactions or residual toxicity b. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 c. 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). d. Participant must be ≥ 18 years of age e. Participant must have adequate organ function, defined as follows: • Absolute neutrophil count ≥ 1,500/μL • Platelets ≥ 100,000/μL • Hemoglobin ≥ 9 g/dL • Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60mL/min using the Cockcroft-Gault equation • Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN • Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN • 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 f. Pre-existing hypertension should be adequately controlled before starting niraparib treatment g. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment. h. 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 prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided may submit an archived specimen. i. 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. Nonchildbearing potential is defined as follows: • ≥45 years of age and has not had menses for >1 year and has a high follicle-stimulating hormone (FSH) level in the postmenopausal ranges confirmed by two FSH measurements • 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, otherwise 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 4.4 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. j. Participant must agree to not breastfeed during the study or for 180 days after the last dose of study treatment. k. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent

Exclusion criteria 1

1. 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 Day1 of protocol therapy Participant has not recovered to Grade1 or baseline from all toxicities associated with previous therapy Participant must not have a known hypersensitivity to niraparib and dostarlimab components or excipients and must not have any hypersensitivity to the treatment used as standard of care in the control arm Participant must not show contraindications to other agents(including chemotherapy)used in this study Participant must not have received a transfusion (platelets or red blood cells) Participant must not have received colony-stimulating factors 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>4weeks and was related to the most recent treatment Participant must not have a diagnosis of Sars-CoV-2 infection at the time of screening Participant must not have any known history of myelodysplastic syndrome or acute myeloid leukemia Participant must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection 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 2 immune-related AE with prior immunotherapy with the exception of non-clinically significant lab abnormalities Participant has a diagnosis of immunodeficiency or has an active autoimmune disease that has required systemic treatment in the past 2years or has received systemic steroid therapy at a dose>10 mg/day or any other form of immunosuppressive therapy within 7days prior to initiating protocol therapy. Local or systemic corticosteroid treatment at a dosage less than or equal to 10 mg/day is allowed Participant has a known history of human immunodeficiency virus Participant has known active hepatitis B or hepatitis C Participant has an active infection requiring systemic therapy Participant must not have a history of interstitial lung disease Participant has had an allogenic tissue/solid organ transplant 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 Has received a live vaccine within 30days of planned start of study therapy while participating in the trial and within90days of the last dose of study medication Women with childbearing potential if they do not agree with the use of highly effective contraceptive methods with low user dependency or to be abstinent from heterosexual intercourse during the treatment period and at least 180days following the last dose of dostarlimab or niraparib and at least 210 days following the last dose of chemotherapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival (OS), defined as the time from randomization to the date of death by any cause

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Sponsor organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Address

Largo Francesco Vito 1

City

Rome

Postcode

00168

Country

Italy

Scientific contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Prof.ssa Domenica Lorusso

Public contact point

Organisation

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Contact name

Prof.ssa Domenica Lorusso

Third parties 3

Locations

4 EU/EEA countries · 33 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 47 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications