iraparib alone or Niraparib and bevacizumab combination in Women with ovarian cancer.

Phase 1

• Conditions: Women with relapsed platinum-sensitive epithelial ovarian cancer; MedDRA version: 20.0Level: PTClassification code 10061328Term: Ovarian epithelial cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10061344Term: Peritoneal neoplasmSystem 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] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

• Registration Number: EUCTR2014-004269-26-DK
• Lead Sponsor: ordic Society of Gynaecological Oncology - Clinical Trial Unit

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-02-13
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 110

Inclusion Criteria

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.
3.Patient consents to perform HRD test.
- Patients with known BRCA status: BRCA positive patients must submit the tissue for HRD test, though these patients need not to wait for HRD test results and can be randomized in HRD positive stratum.
- If tumor tissue is not sufficient to perform HRD test: these patients shall be randomized in HRD negative stratum as HRD unkown.
4.Prior line of therapy: Patients must have received platinum-containing therapy for primary disease.
- 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%.
- Up to one non-platinum-based line of therapy in recurrent setting.
- Patients who are treated with bevacizumab just prior to entering in the trial must not have progressed under or within 3 months after bevacizumab.
- Patients may have participated in a PARP inhibitor trial as first-line maintenance therapy and have not progressed within 3 months after PARP/placebo. Patients who received PARP inhibitor after relapse (definitive or maintenance therapy) are not eligible.
5. Target group: Age 18+
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 though no other prior use of anti-angiogenic therapy
10.Patients may have received a PARP inhibitor as first-line maintenance therapy.
11.Patients must have disease that is measurable according to RECIST or assessable according to the GCIG criteria
12.The patient agrees to complete PROs (QoL questionnaire) during study treatment AND at one additional time point 8 weeks following progression of disease
13.ECOG performance status 0-2
14.Adequate organ function
oAbsolute neutrophil count (ANC) =1,5 x 109/L
oPlatelets >100 x 109/L
oHemoglobin = 9g/dl
oSerum creatinine =1.5x upper limit of normal (ULN) or ?calculated creatinine clearance =50mL/min using Cockcroft-Gault formula
oTotal bilirubin =1.5x ULN
oAspartate aminotransferase (AST) and alanine ?aminotransferase (ALT) =2.5x ULN unless liver metastases are present, in which case they must be =5x ULN.
15.Able to take oral medications
16.Life expectancy of at least 12 weeks
17.Patients must fulfill all inclusions criteria and according to investigator fit to receive niraparib and/or bevacizumab.
18.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 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

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. 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
5. 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
6. 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
7. Gastrointestinal disorders or abnormalities that would interfere with absorption of the study drug
8. 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
9. Known contraindications to PARP inhibitors or VEGF directed therapy
10. Known uncontrolled hypersensitivity to the investigational drugs
11. 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. This also apply to PE & DVT.
12. History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 3 months
13. History of clinically significant hemorrhage in the past 3 months
14. 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)
15. 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
16. 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.
17. Radiographic evidence of cavitation or necrotic tumors with invasion of adjacent major blood vessels
18. Active or chronic hepatitis C and/or B infection
19. Persistence of clinically relevant therapy related toxicity from previous chemotherapy
20. 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 21. Patients must not have any known history of MDS
22. Pat

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified