Randomized, Double-Blind, Phase III Trial of Olaparib vs. Placebo added to Bevacizumab in Maintenance in Patients with Advanced Ovarian, Fallopian Tube, or Peritoneal Cancer after treatment with standard First-Line Treatment, Combining Platinum-Taxane Chemotherapy and concurrent Bevacizumab.
- Conditions
- Patients with advanced FIGO stage IIIB – IV high grade serous or endometrioid ovarian, fallopian tube, or peritoneal cancer treated with standard first-line treatment, combining platinum-taxane chemotherapy and bevacizumab concurrent with chemotherapy and in maintenanceMedDRA version: 18.1Level: PTClassification code 10070908Term: Ovarian cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 18.1Level: PTClassification code 10070907Term: Ovarian cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 18.1Level: PTClassification code 10016187Term: Fallopian tube cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 18.1Level: PTClassification code 10016186Term: Fallopian tube cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 18.1Level: PTClassification code 10016182Term: Fallopian tube cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 18.1Level: PTClassification code 10057529Term: Ovarian cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 18.1Level: PTClassification code 10016180Term: Fallopian tube cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 18.1Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-004027-52-SE
- Lead Sponsor
- ARCAGY-GINECO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 636
I-1. Female Patient must be =18 years of age.
I-2. Signed informed consent and ability to comply with treatment and follow-up.
I-3. Patient with newly diagnosed
I-3-1 Ovarian cancer, primary peritoneal cancer and/or fallopian-tube cancer,
I-3-2 Histologically confirmed (based on local histopathological findings):
· high grade serous (see appendix 2) or
· high grade endometrioid (see appendix 2) or
· other epithelial non mucinous ovarian cancer in a patient with germline BRCA 1 or 2 deleterious mutation
I-3-3 at an advanced stage: FIGO stage IIIB, IIIC, or IV of the 1988 FIGO classification
I-4. Patient who has completed prior to randomization first line platinum-taxane
chemotherapy:
a. Platinum-taxane based regimen must have consisted of a minimum of 6 treatment cycles and a maximum of 9. However if platinum based therapy must be discontinued early as a result of non hematological toxicity specifically related to the platinum regimen, (i.e. neurotoxicity, hypersensitivity etc.), patient must have received a minimum of 4 cycles of the platinum regimen.
b. Intravenous, intraperitoneal, or neoadjuvant platinum based chemotherapy is allowed; for weekly therapy, three weeks are considered one cycle. Interval debulking is allowed.
I-5. Patient must have received prior to randomization a minimum of 3 cycles of
bevacizumab in combination with the 3 last cycles of platinum-based chemotherapy. Bevacizumab treatment should be administered at a dose 15mg/kg q3 weeks up to a total of 15 months.
I-6. Patient must be prior to randomization without evidence of disease (NED) or in complete response (CR) or partial response (PR) from her first line treatment. There should be no clinical evidence of disease progression (physical exam, imagery, CA 125) throughout her first line treatment and prior to study randomization.
I-7. Patient must be randomized at least 3 weeks and no more than 9 weeks after her last dose of chemotherapy (last dose is the day of the last infusion) and all major toxicities from the previous chemotherapy must have resolved to CTC AE grade 1 or better (except alopecia and peripheral neuropathy).
I-8. Patient must have normal organ and bone marrow function:
a. Hemoglobin = 10.0 g/dL.
b. Absolute neutrophil count (ANC) = 1.5 x 109/L.
c. Platelet count = 100 x 109/L.
d. Total bilirubin = 1.5 x institutional upper limit of normal (ULN).
e. Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase
(ASAT/SGOT)) and Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) = 2.5 x ULN, unless liver metastases are present in
which case they must be = 5 x ULN.
f. Serum creatinine = 1.25 x institutional ULN and creatinine clearance > 50 mL/min.
g. Patient not receiving anticoagulant medication who has an International
Normalized Ratio (INR) =1.5 and an Activated ProThrombin Time (aPTT) =1.5 x ULN.
The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or APTT is within therapeutic limits (according to site medical standard) and if the patient is on a stable dose of anticoagulants for at least two weeks at thetime of randomization.
h. Urine dipstick for proteinuria < 2+. If urine dipstick is =2+, 24-hour urine must demonstrate <1 g of protein in 24 hours.
i. Normal blood pressure or adequately treated and controlled hypertension
(systolic BP = 140 mmHg and/or diastolic BP = 90 mmHg).
I-9. Eastern Cooperative Oncology Gro
E-1. Non-epithelial origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors).
E-2. Ovarian tumors of low malignant potential (e.g. borderline tumors), or mucinous carcinoma.
E-3. Patient with synchronous primary endometrial cancer unless both of the following criteria are met:
a. stage < II,
b. Less than 60 years old at the time of diagnosis of endometrial cancer with stage IA or IB grade 1 or 2, or stage IA grade III endometrioid adenocarcinoma
OR = 60 years old at the time of diagnosis of endometrial cancer with stage IA
grade 1 or 2 endometrioid adenocarcinoma.
Patient with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium is not eligible.
E-4. Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer curatively treated in situ cancer of the cervix, DCIS.
E-5. Patient with myelodysplastic syndrome/acute myeloid leukemia history.
E-6. Patient having experienced for at least one cycle, a delay > 2 weeks due to prolonged hematological recovery during the first line chemotherapy.
E-7. Patient receiving radiotherapy within 6 weeks prior to study treatment.
E-8. Major surgery within 4 weeks of starting study treatment and patient must have recovered from any effects of any major surgery.
E-9. Previous allergenic bone marrow transplant.
E-10. Any previous treatment with PARP inhibitor, including olaparib.
E-11. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period (hormonal replacement therapy is permitted as are steroidal antiemetics).
E-12. Current or recent (within 10 days prior to randomization) chronic use of aspirin > 325 mg/day.
E-13. Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
E-14. Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy.
E-15. Clinically significant (e.g. active) cardiovascular disease, including:
a. Myocardial infarction or unstable angina within = 6 months of randomization,
b. NYHA = grade 2 congestive heart failure.
c. Poorly controlled cardiac arrhythmia despite medication (patient with rate
controlled atrial fibrillation are eligible), or any clinically significant abnormal
finding on resting ECG,
d. Peripheral vascular disease grade = 3 (e.g. symptomatic and interfering with
ADL requiring repair or revision).
E-16. Previous Cerebro-Vascular Accident, Transient Ischemic Attack or Sub-
Arachnoids Hemorrhage within 6 months prior to randomization.
E-17. History or evidence of hemorrhagic disorders within 6 months prior to randomization.
E-18. Evidence of bleeding diathesis or significant coagulopathy (in the absence of coagulation).
E-19. History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory in case of suspected brain
metastases. Spinal MRI is mandatory in case of suspected spinal cord compression.
E-20. History or evidence upon neurological examination of central nervous system disease, unless adequately treated with standard medical therapy (e.g. uncontrolled seizures).
E-21. Significant traumatic injury during 4 weeks prior to randomization.
E-22. Non-healing wound, active ulcer or bone fracture. Patient with granulating incisions healing by secondary intention with no evidence of facial de
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