Ovarian, fallopian tube or primary peritoneal recurrent cancer MedDRA version: 20.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: SOC Classification code 10038604 Term: Reproductive system and breast disorders System Organ Class: 10038604 - Reproductive system and breast disorders
Conditions
Interventions
Product Name: Niraparib
Product Code: Niraparib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NIRAPARIB
CAS Number: 1038915-60-4
Other descriptive name: NIRAPARIB
Concentration unit: mg mill
Sponsors
Istituto di Ricerche Farmacologiche Mario Negri IRCCS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 18 years of age or older, female, any race 2. Histologically diagnosed ovarian cancer, fallopian tube cancer or primary peritoneal cancer 3. High grade serous or high grade endometrioid (grade 2 or 3) histology or known to have BRCAmut (somatic or germline) 4. Has received at least 2 previous lines of platinum-containing therapy (not necessarily consecutive), and has disease that was considered platinum sensitive following the penultimate platinum line (more than 6-months period between penultimate platinum regimen and progression of disease) 5. Has responded to the last platinum line (PR or CR) 6. No more than 8 weeks have elapsed from completion of the last platinum regimen and the patient is still not progressing after response 7. Eastern Cooperative Oncology Group (ECOG) performance status of = 1 8. Adequate bone marrow, kidney and liver function, defined as follows: a. Absolute neutrophil count = 1,500/µL b. Platelets = 100,000/µL c. Hemoglobin = 9 g/dL d. Serum creatinine = 1.5 x upper limit of normal (ULN) or calculated creatinine clearance = 30 mL/min using the Cockcroft-Gault equation e. Total bilirubin = 1.5 x ULN (=2.0 in patients with known Gilberts syndrome) OR direct bilirubin = 1 x ULN f. Aspartate aminotransferase and alanine aminotransferase = 2.5 x ULN unless liver metastases are present, in which case they must be = 5 x ULN 9. Patient receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy. 10. Patient must have a negative urine or serum pregnancy test within 7 days prior to taking study treatment if 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 use highly effective contraception throughout the study. Such methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen- only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone- releasing system (IUS), bilateral tubal occlusion, vasectomized partner. In case of vomiting and diarrhea patient should use an additional barrier method. Non-childbearing potential is defined as follows (by other than medical reasons): =45 years of age and has not had menses for >1 year; patients with amenorrhea 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, otherwise the patient must be willing to use highly effective contraception throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. 11. Patient must agree to not breastfeed during the study and for 180 days after the last dose of study treatment. 12. Patient must be able to understand the study procedures and agree to participate in the study by providing written informed consent. 13. Patients must have normal blood pressure or adequately treated and controlled hypertension. (i.e. systolic BP = 140 mmHg and diatolic BP =
Exclusion criteria
Exclusion criteria: 1. Patient simultaneously enrolled in any interventional clinical trial 2. Invasive cancer other than ovarian cancer within 2 years (except basal or squamous cell carcinoma of the skin that has been definitely treated) 3. Patient with known, symptomatic brain or leptomeningeal metastases 4. Patient with immunocompromised status 5. Patient with known active hepatic disease 6. Prior treatment with a known PARP inhibitor 7. Patient who has had major surgery = 3 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects. 8. Patient who has 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. 9. Patient has had radiation therapy encompassing >20% of the bone marrow within 2 weeks prior to day 1 of protocol therapy 10. Patient has had any radiation therapy within 1 week prior to day 1 of protocol therapy. 11. Patient with known hypersensitivity to niraparib components or excipients. 12. Patient has received a transfusion (platelets or red blood cells) = 4 weeks prior to initiating protocol therapy. 13. Patient has received colony stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy. 14. Patient 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. 15. Patient with any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) 16. Patient with a serious, uncontrolled medical disorder. Examples include, but are not limited to, nonmalignant systemic disease, active, uncontrolled infection, 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 17. Patient who might be dependent on the sponsor, CRO, site or the investigator. 18. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of the study are: •to compare the safety profile of niraparib RADAR dosing in terms of occurrence of grade = 3 thrombocytopenia in the first three cycles versus the SmPC approved dosing in patients who either have a baseline body weight =58 and <77kg, or have a baseline body weight =77kg and baseline platelet count <150,000/µL (restricted population); •to evaluate the improvement in the safety profile of niraparib RADAR dosing in terms of occurrence of grade = 3 thrombocytopenia in the first three cycles.;Secondary Objective: •to compare the safety profile of RADAR dosing in terms of occurrence of grade = 3 thrombocytopenia in the first six cycles versus the SmPC approved dosing •to evaluate the improvement in the safety profile of niraparib RADAR dosing in terms of occurrence of grade = 3 thrombocytopenia in the first six cycles oto compare the efficacy of niraparib RADAR dosing vs. the SmPC dosing (300 mg) oto compare the safety profile of RADAR dosing compared with the SmPC dosing (300 mg) oto evaluate the safety of niraparib RADAR •Compliance: to evaluate patients adherence to the two treatment regimens of niraparib (RADAR and SmPC) under study in terms of average administered dose in the first 6 cycles •Pharmacokinetic: to assess the minimum level of niraparib at the steady state, i.e. trough level concentration and the peak level at two hours after the daily dose;Primary end point(s): Rate of patients experiencing a grade =3 thrombocytopenia during the first three cycles.;Timepoint(s) of evaluation of this end point: During the first three cycles | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Rate of patients experiencing a grade =3 thrombocytopenia during the first six cycles;Timepoint(s) of evaluation of this end point: During the first six cycles | — |
Countries
Germany, Italy
Contacts
Public ContactOncology Department
Istituto di Ricerche Farmacologiche Mario Negri IRCCS
Outcome results
None listed