iraparib and niraparib-bevacizumab combination against bevacizumab alone in Women with Homologous Recombination Deficient (HRD) platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancer.
- Conditions
- Homologous Recombination Deficient (HRD) platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancerTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-004269-26-FI
- Lead Sponsor
- ordic Society of Gynaecological Oncology (NSGO)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 132
Study population
1. Recurrent platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancer (platinum sensitivity defined as no recurrence within 6 months of last receipt of platinum/chemotherapy).
2. High-grade serious or high-grade endometrioid histology. Other histological types are allowed if documented BRCA mutation.
3. Patient consents to perform HRD test.
4. HRD test positive.
5. Prior line of therapy: Patients must have received platinum-containing therapy for primary disease.
o No limits on number of platinum-based therapies. Population of patients who has previously received = 3 lines of therapy for relapsed disease will be capped at 40%.
o Up to one non-platinum-based line of therapy in recurrent setting.
o Patients who are treated with bevacizumab just prior to entering in the trial must not have progressed under or within 3 months after bevacizumab.
Other inclusion criteria:
6. Histological confirmed ovarian, fallopian tube or peritoneal cancers
7. Patients must give informed consent
8. Patients may have undergone primary or interval debulking surgery
9. Patients may have received bevacizumab or other anti-angiogenic therapy
10. Patients must have disease that is measurable according to RECIST or assessable according to the GCIG CA-125 criteria
11. The patient agrees to complete PROs (QoL questionnaire) during study treatment AND at one additional time point 8 weeks following progression of disease
12. ECOG performance status 0-2
13. Adequate organ function
o Absolute neutrophil count (ANC) =1,5 x 109/L
o Platelets >100 x 109/L
o Hemoglobin = 9g/dl
o Serum creatinine =1.5x upper limit of normal (ULN) or calculated creatinine clearance =50mL/min using Cockcroft-Gault formula
o Total bilirubin =1.5x ULN
o Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5x ULN unless liver metastases are present, in which case they must be =5x ULN.
14. Able to take oral medications
15. Life expectancy of at least 12 weeks
16. Patients must be fit to receive niraparib and/or bevacizumab
17. Women of childbearing potential must use adequate birth control for the duration of study participation
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 66
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 66
1. Ovarian sarcomas, small cell carcinoma with neuroendocrine differentiation, non-epithelial cancers and cancer types not mentioned in the inclusion criteria 2. Concurrent cancer therapy
3. Concurrent treatment with an investigational agent or participation in another clinical trial
4. Prior treatment with PARP inhibitors
5. Major injuries or surgery within the past 21 days prior to start of study treatment with incomplete wound healing and/or planned surgery during the on-treatment study period
6. Previous malignant disease: patients are not eligible for the study if diagnosis, detection or treatment of invasive cancer (other than ovarian cancer; with the exception of basal or squamous cell carcinoma of the skin that was definitively treated) was detected within 2 years prior to randomization
7. Active infections or other serious underlying significant medical illness, abnormal laboratory finding or psychiatric illness/social situation that would, in the Investigator’s judgment, makes the patient inappropriate for this study
8. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
9. History of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess. Evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction
10. Known contraindications to PARP inhibitors or VEGF directed therapy
11. Known uncontrolled hypersensitivity to the investigational drugs
12. History of major thromboembolic event defined as:
? Uncontrolled pulmonary embolism (PE)
? Deep venous thrombosis (DVT)
? Other related conditions, though patients with stable therapeutic anticoagulation for more than three months prior randomization are eligible for this study
13. History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 3 months
14. History of clinically significant hemorrhage in the past 3 months
15. Uncontrolled and/or symptomatic CNS metastasis or leptomeningeal carcinomatosis (Dexamethasone/prednisone therapy will be allowed if administered as stable dose for at least one month prior randomization)
16. Significant cardiovascular diseases, including uncontrolled hypertension, clinically relevant cardiac arrhythmia, unstable angina or myocardial infarction within 6 months prior to randomization, congestive heart failure > NYHA III, severe peripheral vascular disease, QT prolongation >470 msec ,clinically significant pericardial effusion
17. Pregnancy or breastfeeding. Patients with preserved reproductive capacity, unwilling to use a medically acceptable method of contraception for the duration of the trial and for 3 months afterwards.
18. Radiographic evidence of cavitation or necrotic tumors with invasion of adjacent major blood vessels
19. Active or chronic hepatitis C and/or B infection
20. Persistence of clinically relevant therapy related toxicity from previous chemotherapy
21. Proteinuria as demonstrated by: (a) urine protein: creatinine (UPC) ratio >/= 1.0 at screening OR (b) urine dipstick for proteinuria >/=2+ (patients discovered to have >/=2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hr urine collection and must demonstrate 22. Patients must not have any known history of MDS
23. Patients must not have k
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method