Phase II randomised, double blind, multicentre study to assess the efficacy of AZD2281 in the treatment of patients with platinum sensitive serous ovarian cancer following treatment with two or more platinum containing regimens
- Conditions
- platinum sensitive serous ovarian cancerMedDRA version: 9.1Level: LLTClassification code 10033128Term: Ovarian cancer
- Registration Number
- EUCTR2008-003439-18-FR
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 250
1.Provision of fully informed consent prior to any study specific procedures.
2.Patients must be > 18 years of age.
3.Female patients with histologically diagnosed serous ovarian cancer or recurrent serous ovarian cancer (including primary peritoneal and fallopian tube cancer). This includes patients who have developed recurrent ovarian cancer with macroscopic peritoneal metastases outside the pelvis or distant metastases. Patients with spinal cord compression may be considered if they have received definitive treatment for this and evidence of clinically stable disease for 28 days.
4.Patients must have completed at least 2 previous courses of platinum containing therapy:
a. For the penultimate chemotherapy course prior to enrolment on the study:
-A patient’s treatment must have contained a platinum agent (carboplatin or cisplatin per normal clinical practice; there are no other specific requirements).
-A patient must have been defined as platinum sensitive after this treatment; defined as disease progression greater than 6 months after completion of their last dose of platinum chemotherapy.
b.For the last chemotherapy course prior to enrolment on the study:
-Patients must have received a platinum containing regimen (carboplatin or cisplatin).
-Patients must have demonstrated an objective stable maintained response (partial or complete response) and this response needs to be maintained to permit entry into the study.
• This response can be confirmed as per RECIST, (note the assessment does not need to be confirmed >4 weeks later) and/or a CA-125 GCIG confirmed response (at least a 50% reduction in CA-125 levels from the last pre-treatment sample, confirmed 28 days later).
-Patients must be treated on the study within 8 wks of completion of their final dose of the platinum containing regimen.
-Chemotherapy course must have consisted of a minimum of 4 treatment cycles.
5.Formalin fixed, paraffin embedded tumour sample from the primary or recurrent cancer must be available for central testing. If there is not written confirmation of the availability of an archived tumour sample prior to enrolment the patient is not eligible for the study.
6.Pre-treatment CA-125 measurements (taken at least 7 days apart, at the same local lab as specified in Table 4) must meet criterion specified below:
-If the 2nd value is within ULN a patient is eligible to enter the study
-If the 2nd value is greater than ULN, it must no more than 15% greater than the 1st.
7.Patients must have normal organ and bone marrow function measured within 7 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)
8.ECOG performance status = 2 (see Appendix F)
9.Patients must have a life expectancy = 16 weeks.
10.Evidence of non-childbearing status: negative urine or serum pregnancy test within 7 days of study treatment for women of childbearing potential, or postmenopausal status
Postmenopausal is defined by any one of the following:
§natural menopause with last menses >1 year ago;
§radiation-induced oophorectomy with last menses >1 y
1.Patients with low grade ovarian carcinoma. (Grade 1)
2.Patients who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen prior to enrolment on the study.
3.Previous treatment with PARP inhibitors including AZD2281.
4.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.
5.Patients receiving any chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study entry (or a longer period depending on the defined characteristics of the agents used). Patients may continue the use of corticosteroids, provided the dose is stable during the study and has been started at least 4 weeks prior to enrolment.
6.Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required.
7.Major surgery within 2 weeks of starting the study and patients must have recovered from any effects of any major surgery.
8.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.
9.Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication (eg, partial bowel obstruction or malabsorption).
10.Patients requiring treatment with potent inhibitors or inducers of CYP3A4 (see Section 6.4.1 for guidelines and wash out periods).
11.Pregnant or breast feeding women.
12.Immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
13.Patients with known hepatic disease (ie, Hepatitis B or C).
14.Persistent toxicities (grade 2 or greater) caused by previous cancer therapy (excluding alopecia).
15.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
16.Previous randomisation to treatment in the present study.
17.Treatment with any investigational product during the last 28 days (or a longer period depending on the defined characteristics of the agents used).
18.Patients with a known hypersensitivity to AZD2281 or any of the excipients of the product.
19.Patients currently experiencing seizures or who were currently being treated with only anti-epileptics for seizures (use of anti-epileptic drugs to control pain is allowed in patients not suffering from seizures unless drug is excluded due to CYP3A4 induction - phenytoin, carbamazepine, phenobarbitone, see Section 6.4.1.
20.Optional pharmacogenetics sample only:
·previous allogeneic bone marrow transplant
·blood transfusion in the last 120 days prior to entry to the study
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