A Phase IIIb, Single-arm, Open-label Multicentre Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed non-Germline BRCA Mutated Ovarian Cancer Patients who are in Complete or Partial Response Following Platinum based Chemotherapy
- Conditions
- on Germline BRCA Mutated Ovarian CancerMedDRA version: 20.0Level: 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
- EUCTR2017-002767-17-AT
- 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 informed consent prior to any study specific procedures
2. Patients must be =18 years of age
3. Female patients with histologically diagnosed relapsed HGSOC (including primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer
4. Documented gBRCA1/2 mutation status Evidence that the patients do not have a gBRCA mutation that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental / lead to loss of function). gBRCA1 and/or gBRCA2 variants that are classified as
Variants of uncertain clinical significance or Variant of unknown significance (VUS) are eligible, as well as Variant, favor polymorphism or benign polymorphism.
Evidence of the absence of a somatic BRCA mutation is not required.
Patients with a tumour BRCA test result only must undergo a gBRCA test to determine whether the BRCA aberration is germline or somatic in origin. If this analysis identifies the aberration as germline the patient is not eligible
5. 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:
• Treatment must have contained a platinum agent (e.g. carboplatin or cisplatin per standard clinical practice; there are no other specific requirements)
• Patient was platinum sensitive after this treatment; defined as disease progression greater than 6 months after completion of their last dose of platinum chemotherapy
• Maintenance treatment is allowed at the end of the penultimate platinum regimen, including bevacizumab
(b) For the last chemotherapy course immediately prior to enrolment on the study
• Patients must be, in the opinion of the investigator, in response (partial or complete radiological response), or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy), and no evidence of a rising CA-125, as defined below, following completion of this chemotherapy course
• Patient must have received a platinum based chemotherapy regimen (carboplatin or cisplatin) and have received at least 4 cycles of treatment
• Patients must not have received bevacizumab during this course of treatment
• Patients must not have received any investigational agent during this course of treatment
• Patients must initiate treatment within 8 weeks of their last dose of chemotherapy (last dose is the day of the last infusion)
6. Pre-treatment CA-125 measurements must meet criterion specified below:
• If the first value is within upper limit of normal (ULN) the patient is eligible to be enrolled and a second sample is not required
• If the first value is greater than ULN a second assessment must be performed at least 7 days after the 1st. If the second assessment is = 15% more than the first, the patient is not eligible
7. Patients must have normal organ and bone marrow function measured within 28 days of starting study treatment, as defined below. In the event of minor deviations from these values which would lead to screen failure, repeat testing within the 28-day screening period (limited to the tests listed below) is allowed before the patient is declared a screen failure.
8. ECOG performance status 0-1
9. Patients must have a life expectancy =16 weeks
10. Postmenopausal or evidence of non-childbearing status for women of childbearing potential :negative urine or serum pregnancy test within 28 days of study treatment and co
Patients should not enter the study if any of the following exclusion criteria are fulfilled.
Those asterisked* should be excluded before a request can be considered to perform a gBRCA test prior to full screening. Investigator judgement of patient's potential eligibility to the study should be
assessed as per Protocol Table 1 and by reviewing the below exclusion criteria).
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)*
2. Previous enrolment in the present study*
3. Participation in another clinical study with an investigational product (IP) during the most recent chemotherapy course*
4. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to start of study treatment
5. Any previous treatment with PARP inhibitor, including olaparib*
6. Patients with a germline BRCA mutation that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental / lead to loss of function).
7. 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 (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*
8. Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks*.
9. Concomitant use of known strong (e.g., phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5
weeks for phenobarbital and 3 weeks for other agents*
10. Persistent toxicities (= Grade 2 Common Terminology Criteria for Adverse Event (CTCAE) adverse event) caused by previous cancer therapy, excluding alopecia
11. Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML*
12. Patients with symptomatic uncontrolled brain metastases. 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. Patients with spinal cord compression unless considered to have
received definitive treatment for this and evidence of clinically stable disease (SD) for 28 days*
13. Major surgery within 3 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
14. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
15. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication*
16. Currently pregnant (confirmed with a positive pregnancy test) or breastfeeding women*
17. Immuno-compromised patients e.g., Human Immunodeficiency Virus (HIV) requiring treatment or active Hepatitis B or C*
18. Patients with
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