A Phase II, Open-Label, Randomised, Comparative, Multicentre Study to Compare the Efficacy and Tolerability of Olaparib in Combination with Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone in Patients with Platinum Sensitive Advanced Serous Ovarian Cancer - ND

Phase 1

• Conditions: serous ovarian cancer; MedDRA version: 12.1Level: LLTClassification code 10033128Term: Ovarian cancer

• Registration Number: EUCTR2009-015970-36-IT
• Lead Sponsor: ASTRAZENECA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-02-26
• Last Update Posted: 12 July 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 150

Inclusion Criteria

1.Provision of fully informed consent prior to any study specific procedures 2.Patients must be > 18 years of age. 3.Histologically or cytologically diagnosed ovarian cancer with a serous histology or a serous component, including primary peritoneal and fallopian tube cancer. 4.Patients who have received no more than 3 previous platinum containing regimens and were progression free, in the opinion of the Investigator, for a minimum of 6 months following completion of their last platinum containing regimen, prior to randomisation in the study. 5.At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements. 6.Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below: -Haemoglobin ≥ 9.0 g/dL -Absolute neutrophil count (ANC) ≥ 1.5 x 109/L -White blood cells (WBC) > 3x109/L -Platelet count ≥ 100 x 109/L -Total bilirubin ≤ 1.5 x institutional upper limit of normal -AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN -Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN) -Creatinine clearance (using Cockcroft-Gault) within normal range (> 50 mL/min) 7.ECOG performance status ≤ 2 (see Appendix F) 8.Patients must have a life expectancy ≥ 12 weeks. 9.Evidence of non-childbearing status for women of childbearing potential, or postmenopausal status: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1 Postmenopausal is defined as one of the following: -Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments, -LH and FSH levels in the post menopausal range for women under 50, -radiation-induced oophorectomy with last menses >1 year ago, -chemotherapy-induced menopause with >1 year interval since last menses, -or surgical sterilisation (bilateral oophorectomy or hysterectomy). 10.Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Patients receiving any systemic anticancer chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment. 2.Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, Ductal Carcinoma in Situ (DCIS), stage 1 grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥ 5 years. 3.Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. 4.Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. 5.Patients with severe hypersensitivity reactions to paclitaxel, macrogolglycerol ricinoleate (polyoxyl castor oil) or to any of the excipients in paclitaxel. 6.Patients with a known hypersensitivity to olaparib or any of the excipients of the product. 7.Patients with a history of severe allergic reaction to carboplatin or other platinum containing compounds. Patients who require desensitisation procedures for further platinum-based treatment should not be included. 8.Hypersensitivity to pre-medications required for treatment with paclitaxel/ carboplatin. 9.Any previous treatment with a PARP inhibitor, including olaparib. 10.Patients receiving the following classes of inhibitors of CYP3A4 (see Section 5.6.1 for guidelines and wash out periods). -Azole antifungals -Macrolide antibiotics -Protease inhibitors 11.Persisting toxicities (>CTCAE grade 2) caused by previous cancer therapy. 12.Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. 13.Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication. 14.Breast feeding women. 15.Known immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV). 16.Patients with known active hepatic disease (i.e., Hepatitis B or C). 17.Patients with uncontrolled seizures. 18.Previous randomisation in this study. 19.Participation in another clinical study with administration of an investigational product during the last 14 days. 20.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the efficacy of olaparib when given in combination with paclitaxel and carboplatin to paclitaxel and carboplatin alone, by assessment of Progression Free Survival (PFS).(Independent Central Review);Secondary Objective: The secondary objectives of this study are: ?To compare the efficacy of olaparib when given in combination with paclitaxel and carboplatin to paclitaxel and carboplatin alone, by assessment of Overall Survival (OS), percent change in tumour size, Objective Response Rate (ORR), Ovarian Cancer Response Rate (a composite of CA-125 Response Rate [Gynecologic Cancer InterGroup {GCIG} criteria] and/or RECIST Response Rate), and CA-125 response rate (GCIG criteria). ?To compare the safety and tolerability of olaparib when given in combination with paclitaxel and carboplatin to paclitaxel and carboplatin alone.;Primary end point(s): Progression Free Survival (PFS) evaluated by RECIST 1.1 (Independent Central Review)