Olaparib Monotherapy versus Physician's Choice Chemotherapy in the Treatment of Ovarian Cancer in Patients carrying BRCA Mutations
- Conditions
- Platinum Sensitive Relapsed 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
- EUCTR2014-003438-20-IT
- 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
- 270
- Patients must be = 18 years of age during randomisation
- Female patients with histologically diagnosed relapsed high grade
serous ovarian cancer (including primary peritoneal and/or fallopian
tube cancer) or high grade endometrioid cancer (please refer to
Appendix H). Patients are eligible to undergo BRCA testing even if they
have not yet had recurrence or progression of disease >6 months (>/=183 days) after completion of their last platinum therapy
- Documented germline mutation in BRCA1 and/or BRCA2 that is
predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)
- At least one lesion (measurable and/or non-measurable) that can be
accurately assessed at baseline by CT/MRI and is suitable for repeated
assessment.
- Patients must have received at least 2 prior platinum based previous
lines of chemotherapy for ovarian cancer prior randomisation
- Patients must be partially platinum sensitive (defined as progression 6
-12 months after the end of the last platinum based chemotherapy) or
platinum sensitive (defined as progression > 12 months after the end of
the last platinum based chemotherapy).
- Patients must be suitable to start treatment with single agent
chemotherapy based on physician's choice of weekly paclitaxel or
topotecan or pegylated liposomal doxorubicin or gemcitabine.
- Patients must have normal organ and bone marrow function measured
within 28 days of randomisation,
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Patients must have a life expectancy = 16 weeks
- Postmenopausal or evidence of non-childbearing status for women of childbearing potential
- Formalin fixed, paraffin embedded tumour sample from the primary or
recurrent cancer must be available for central testing
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 164
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 106
-BRCA 1 and/or BRCA2 mutations that are considered to be non
detrimental (e.g., Variants of uncertain clinical significance or Variant
of unknown significance or Variant, favor polymorphism or benign
polymorphism etc.)
- Previous randomisation in the present study
- Exposure to any investigational product within 30 days or 5 half lives
(whichever is longer) prior to randomisation
- Any previous treatment with a PARP inhibitor, including olaparib.
- Patients who have platinum resistant or refractory disease defined as progression during or within 6 months of their last platinum based chemotherapy
- 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. Patients with history of primary 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
randomisation
- Clinical significant abnormality on resting ECG
- Patients receiving any systemic chemotherapy within 3 weeks prior to
first randomisation (or a longer period depending on the defined
characteristics of the agents used) or radiotherapy within 2 weeks prior
to randomisation.
- Previous single agent exposure to the selected chemotherapy regimen
for randomisation
- Concomitant use of known potent CYP3A4/5 inhibitors such as
ketoconazole, itraconazole, boosted protease inhibitors( ritonavir, indinavir, saquinavir,
telithromycin, nelfinavir, boceprevir, telaprevir) and clarithromycin.
- Persistent toxicities (> Common Terminology Criteria for Adverse Event
grade 2) caused by previous cancer therapy, excluding alopecia and
CTCAE grade 2 peripheral neuropathy.
- Patients with myelodysplastic syndrome/treatment related acute
myeloid leukaemia (t-AML)
- Patients with symptomatic uncontrolled brain metastases.
- Major surgery within 2 weeks of starting study treatment and patients
must have recovered from any effects of any major surgery. - Patients considered a poor medical risk due to a serious, uncontrolled
medical disorder, non-malignant systemic disease or active, uncontrolled
infection.
- Patients unable to swallow orally administered medication and patients
with gastrointestinal disorders likely to interfere with absorption of the
study medication.
- Breastfeeding women.
- Patients with a known hypersensitivity to olaparib or any of the
excipients of the product.
- Patients with known active hepatitis B or C or HIV.
- Previous allogeneic bone marrow transplant or double umbilical cord
blood transplantation
- Whole blood transfusions in the last 120 days prior to randomisation
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