To determine the efficacy of olaparib versus placebo on progression free survival (PFS).
ID
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Progression Free Survival
Secondary outcome
1. To determine the efficacy of olaparib maintenance monotherapy compared to
placebo in BRCA mutated relapsed ovarian cancer patients who are in complete or
partial response following platinum based chemotherapy by assessment of overall
survival (OS), time to earliest progression by RECIST or Cancer Antigen-125
(CA-125), or death, and time from randomisation to second progression (PFS2).
2. To compare the effects of olaparib maintenance monotherapy compared to
placebo on the rate of deterioration of Health-related Quality of Life (HRQoL)
as assessed by the trial outcome index (TOI) of the Functional Assessment of
Cancer Therapy -Ovarian (FACT-O) in BRCA mutated relapsed ovarian cancer
patients who are in complete or partial response following platinum based
chemotherapy.
3. To assess efficacy of olaparib in patients identified as having a
deleterious or suspected deleterious variant in either of the BRCA genes using
variants identified with current and future BRCA mutation assays (gene
sequencing and large rearrangement analysis).
4. To determine the exposure to olaparib in patients receiving olaparib
maintenance monotherapy
5. Time from randomisation to first subsequent therapy or death (TFST), or time
from randomisation to second subsequent therapy or death (TSST) or time from
randomisation to study treatment discontinuation or death (TDT).
Safety:
To assess the safety and tolerability of olaparib maintenance monotherapy in
BRCA mutated relapsed ovarian cancer patients
Background summary
Ovarian cancer is the fifth most common cause of death from cancer in women.
The incidence of ovarian cancer increases with age and is most prevalent in the
eighth decade of life. More than 70% of the patients are diagnosed with
advanced disease and less than 40% of women with ovarian cancer are cured. The
standard therapy for advanced ovarian cancer consists of radical debulking
surgery followed by post-operative platinum-based first-line chemotherapy.
Olaparib (AZD2281, KU-0059436) is a potent Polyadenosine 5*diphosphoribose
[poly (ADP ribose)] polymerisation (PARP) inhibitor (PARP-1, -2 and -3). PARP
enzymes are essential for repairing DNA. Olaparib can stop or block de PARP
activity. Tumors with HR deficiencies (HRD), such as ovarian cancers in
patients with BRCA1/2 mutations, cannot accurately repair the DNA damage, which
may become lethal to cells as it accumulates. In such tumour types, olaparib
may offer a potentially efficacious and less toxic cancer treatment compared
with currently available chemotherapy regimens. This Phase III study will
determine the efficacy by progression free survival (PFS) (using blinded
independent central review (BICR) according to modified Response Evaluation
Criteria In Solid Tumours (RECIST) 1.1) of olaparib maintenance monotherapy
compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in
complete or partial response following platinum based chemotherapy.
Study objective
To determine the efficacy of olaparib versus placebo on progression free
survival (PFS).
Study design
Phase 3, randomised, double-blind, placebo controlled study
Randomisation 2:1 with:
Olaparib 300 mg twice daily
Placebo twice daily
Intervention
Treatment with Olaparib 300 mg or Placebo.
Study burden and risks
Patient will get a CT scan or MRI scan every 12 weeks (RECICT). assessments
will be done on a regular base, like physical examination, vital signs, blood
sampling, ECGs. Pregnancy or breastfeeding is not allowed.
The risks associated with the use of olaparib are:
Anemia, neutropenea, lymphopenia, thrombocytopenie, heartburn, nausea,
dizziness, diarrhea, vomiting and fatigue.
Louis Pasteurlaan 5
Zoetermeer 2719 EE
NL
Louis Pasteurlaan 5
Zoetermeer 2719 EE
NL
Listed location countries
Age
Inclusion criteria
• Patients must be >= 18 years of age. ;• Female patients with histologically diagnosed relapsed high grade serous ovarian cancer (including primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer.;• Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function).;• Patients who have received at least 2 previous lines of platinum containing therapy prior to randomisation ;• 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, following completion of this chemotherapy course;• Patient must have received a platinum based chemotherapy regimen (e.g. carboplatin or cisplatin) and have received at least 4 cycles of treatment
Exclusion criteria
• Involvement in the planning and/or conduct of the study (applies to;both AstraZeneca staff and/or staff at the study site).;• Patients who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen prior to enrolment on the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-001211-75-NL |
| ClinicalTrials.gov | NCT01874353 |
| CCMO | NL45018.031.13 |