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 (MITO 33)
- Conditions
- Recurrent ovarian, fallopian tube or primary peritoneal cancer.MedDRA version: 20.0Level: PTClassification code 10061344Term: Peritoneal neoplasmSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10066697Term: Ovarian cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10016180Term: Fallopian tube cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000146-33-GR
- Lead Sponsor
- FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS UNIVERSITA' CATTOLICA DEL SACRO CUORE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 427
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 (e.g. gastrointestinal disorders, creatinine renal clearance decreased, blood urea increased, blood alkaline phosphatase increased, aspartate aminotransferase increased, liver function test abnormal, blood sodium decreased, blood potassium decreased, blood calcium decreased, blood magnesium decreased, blood bilirubin increased, blood creatinine increased, blood uric acid increased)
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 adeguately 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 (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.
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 (by other than medical reasons):
? =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 m
a. Participant must not be simultaneously enrolled in any interventional clinical trial
b. 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)
c. Participant must not have had major surgery = 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects.
d. 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.
e. 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.
f. Participant has not recovered to Grade 1 or baseline from all toxicities associated with previous therapy.
g. 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
h. Participant must not show contraindications to other agents (including chemotherapy) used in this study
i. Participant must not have received a transfusion (platelets or red blood cells) = 4 weeks prior to initiating protocol therapy.
j. Participant must not have received colony-stimulating factors (eg, GCSF, GMCSF,or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy.
k. Participant has had any known Gr 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment.
l. Participant must not have a diagnosis of Sars-CoV-2 infection at the time of
screening
m. Participant must not have any known history of MDS or AML
n. 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
o. Participant must not have had diagnosis, detection, or treatment of another type of cancer = 3 years prior to initiating protocol therapy (except basal or SCC of the skin and cervical cancer that has been definitively treated)
p. Participant must not have known, symptomatic brain or leptomeningeal metastases
q. Patient experienced = Gr 2 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.
r. Participant has a diagnosis of immunodeficiency or 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) or has received systemic steroid therapy at a dose > 10 mg/day or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy. Local or systemic corticosteroid treatment at a dosage less than or equal to 10 mg/day is allowed.
s. Replacement therapy (eg.thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary isufficiency etc.) is not considered a form of systemic treatment.
t. Participant has a known history of
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the overall survival (OS);Secondary Objective: •To assess progression free survival<br>•To assess the time to first subsequent therapy <br>•To assess the response rate <br>•To assess the safety and tolerability of patients receiving chemotherapy or TSR 042 + Niraparib <br>•To assess patient-reported outcome (PRO) of patients receiving chemotherapy vs the combination of TSR 042 and Niraparib;Primary end point(s): Overall survival (OS) defined as the time from the date of treatment initiaion to the date of death;Timepoint(s) of evaluation of this end point: 4 years
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Progression-free survival (PFS); Time to first subsequent therapy (TFST); ORR per RECIST 1.1; AE (Adverse Events)/ treatment-emergent (TEAEs) and laboratory abnormalities evaluated according to CTCAE version 5.0; Quality of life and Patient-reported outcome (PRO) with EORTC QLQC30, EORTC QLQOV28, and EQ-5DL;Timepoint(s) of evaluation of this end point: 4 years; 4 years; 4 years; 4 years; 4 years