Phase III Trial of Olaparib vs. Placebo in Patients with Advanced 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 Maintenance

Phase 1

• Conditions: Patients with advanced FIGO stage IIIB – IV high grade epithelial ovarian, fallopian tube, or peritoneal cancer treated with standard first-line treatment; MedDRA version: 21.1Level: PTClassification code 10070908Term: Ovarian cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10070907Term: Ovarian cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-004027-52-DE
• Lead Sponsor: ARCAGY Research

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-05-27
• Last Update Posted: 21 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 786

Inclusion Criteria

I-1. Female Patients must be =18 years of age.
I-2. Signed informed consent and ability to comply with treatment and follow-up.
I-3. Patients with newly diagnosed, histologically confirmed, advanced (FIGO stage IIIB, IIIC, or IV of the 1988 FIGO classification) high grade serous or high grade endometrioid (based on local histopathological findings) ovarian cancer, primary peritoneal cancer and / or fallopian-tube cancer or other epithelial non mucinous ovarian cancer in a patient with germline BRCA 1 or 2 deleterious mutation.
I-4. Patients who have 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.), patients 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. Patients must have received prior to randomization a minimum of 3 cycles of bevacizumab in combination with the 3 last cycles of platinum-based chemotherapy. Only in case of interval debulking surgery, it is allowed to realize only 2 cycles of bevacizumab in combination with the last 3 cycles of platinium-based chemotherapy. Bevacizumab treatment should be planned for maintenance phase.
I-6. Patients must be prior to randomization without evidence of disease (NED) or in complete response (CR) or partial response (PR) from their first line treatment. There should be no clinical evidence of disease progression (physical exam, imagery, CA 125) throughout their first line treatment and prior to study randomization.
I-7. Patients must be randomized at least 3 weeks and no more than 9 weeks after their 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 peripherical neuropathy).
I-8. Patients must have normal organ and bone marrow function:
a. Haemoglobin = 10.0 g/dL, with no red blood cells transfusion in the past 28 days
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,
g. Patients not receiving anticoagulant medication who have 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 oral anticoagulants, dose has to be stable for at least two weeks at the time 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/o

Exclusion Criteria

-Non-epithelial origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors).
-Ovarian tumors of low malignant potential (e.g. borderline tumors), or mucinous carcinoma.
-Patients with synchronous primary endometrial cancer unless both of the following criteria are met:
-stage < II,
-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 carcinoma
OR = 60 years old at the time of diagnosis of endometrial cancer with stage IA grade 1 or 2 endometrioid carcinoma.
-Patients with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium are not eligible.
-Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer curatively treated in situ cancer of the cervix, ductal carcinoma in situ .
Patients with history of primary triple negative breast cancer may be eligible provided they completed their definitive anticancer treatment more than 3 years ago and they remain breast cancer disease free prior to start of study treatment.
-Patients with myelodysplastic syndrome/acute myeloid leukemia history.
-Patients having experienced a delay > 2 weeks in the chemotherapy course administration due to prolonged hematological recovery.
-Patients receiving radiotherapy within 6 weeks prior to study treatment.
-Major surgery within 4 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
-Previous allogenic bone marrow transplant.
-Any previous treatment with PARP inhibitor, including olaparib.
-Administration of other simultaneous chemotherapy drugs, any other anticancer therapy or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial treatment period
-Current or recent (within 10 days prior to randomization) chronic use of aspirin > 325 mg/day.
-Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
-Prior history of hypertensive crisis (CTC-AE grade 4) or hypertensive encephalopathy.
-Clinically significant cardiovascular disease, including:
-Myocardial infarction or unstable angina within = 6 months of randomization,
-NYH = grade 2 congestive heart failure (CHF),
-Poorly controlled cardiac arrhythmia despite medication (patients with rate controlled atrial fibrillation are eligible), or any clinically significant abnormal finding on resting ECG,
-Peripheral vascular disease grade = 3 (e.g. symptomatic and interfering with activities of daily living [ADL] requiring repair or revision).
-Previous Cerebro-Vascular Accident, Transient Ischemic Attack or Sub- Arachnoids Hemorrhage within 6 months prior to randomization.
-History or evidence of hemorrhagic disorders within 6 months prior to randomization.
-Evidence of bleeding diathesis or significant coagulopathy
-History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression.
-History or evidence upon neurological examination of central nervous system disease, unless adequately treated with standard medical therapy .
-Significant traumatic injury during 4 weeks prior to randomization.
-Non-healing wound, active ulcer or bone fr

Study & Design

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