The primary purpose of the study is to determine the efficacy of AZD2281 compared to placebo in serous ovariancancer platinum sensitive patients and in a defined HRD subset.
ID
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
PFS as evaluated by RECIST
Secondary outcome
Efficacy: OS, best overall response, duration of response, CA-125 response
(GCIG criteria), time to progression by CA-125 (GCIG criteria) or RECIST,
Quality of Life (QoL) and disease related symptoms.
Measurement of candidate biomarkers (including but not limited to ATM,
MRE-11, MDC1, BRCA1/2) to identify the Homologous Recombination
Deficient subset of tumours for correlation with benefit/risk of treatment with
AZD2281.
Safety: AEs, physical examination, vital signs including BP, pulse, ECG and
laboratory findings including clinical chemistry, haematology and urinalysis.
Background summary
AZD2281 monotherapy has demonstrated significant anti-tumour activity, (while
being well
tolerated) for ovarian cancer patients (previously treated with platinum
agents) harbouring
mutations in BRCA1 or BRCA2 (AstraZeneca, unpublished data). Many studies have
indicated BRCA1/2 mutations and other BRCA1/2 defects are predominantly found
within the
serous subset of ovarian cancer patients. It is therefore hypothesised that
AZD2281 will have
significant anticancer activity in a large proportion of serous ovarian cancer
patients. Please see page 25 of the study protocol
Study objective
The primary purpose of the study is to determine the efficacy of AZD2281
compared to placebo in serous ovarian
cancer platinum sensitive patients and in a defined HRD subset.
Study design
The study is a randomised, double blind, multi-centre study in platinum
sensitive serous
ovarian cancer patients who have received 2 or more previous platinum
containing regimens.
Platinum sensitivity is defined as disease progression greater than 6 months
after completion
of their penultimate platinum regimen (from last dose) prior to enrolling on
this study. In the
last platinum regimen prior to enrolling on this study, patients must have
demonstrated an
objective stable maintained response (complete, or partial response by GCIG
and/or RECIST)
and this response needs to be maintained to allow entry to the study.
The two platinum regimens do not necessarily have to be sequential.
Patients will be randomised within 8 weeks after their last dose of the
platinum containing
regimen. Randomisation will be stratified by time to disease progression (>6-12
months and
>12 months, in the penultimate platinum therapy prior to enrolment), objective
response (CR
or PR, in the last platinum therapy prior to enrolment) and whether a patient
is of Jewish
descent (yes or no).
Intervention
Patients will be randomised in a 1:1 ratio (AZD2281:matching placebo) to one of
2 arms:
1. AZD2281 400mg bid
2. AZD2281 matching placebo bid
Study burden and risks
* Burden: Patiens will be asked to come to the site 14 times during the first 6
months.
Screening 2 - 2.5h = 30 minutes physical exam + anamnesis + Lab 30 min + 30
min CT + 30 min ECG + 30 min QoL
2nd Screening (if indicated) = Lab 15 min
First 8 weeks (2 cycles)= once a week - 30 minutes per visit
Every month / every two months - 1h visit
Expected duration study from previous clinical experience: 6-12 months, until
disease progression
Total patient visit time based on expected study duration: 10-16h
* Risks are the possible side-effects of the study medication and risks
associated with the study procedures like blood draws, CT- or MRI-scans and ECG.
The side effects most commonly associated with AZD2281 are: anaemia,
neutropenia and thrombocytopenia, nausea, vomiting and fatigue.
Alderley Park, Macclesfield -
Parksland, Cheshire SE1 K/1
GB
Alderley Park, Macclesfield -
Parksland, Cheshire SE1 K/1
GB
Listed location countries
Age
Inclusion criteria
1. Provision of voluntary obtained informed consent prior to any study specific procedures.
2. Female patients, > 18 years of age, with histologically diagnosed serous ovarian cancer or recurrent serous ovarian cancer with a histology type of serous, or a serous component and who have completed at least 2 previous courses of platinum containing therapy (e.g. carboplatin or cisplatin)
3. Formalin fixed, paraffin embedded tumour sample from the cancer must be available for central testing.
Exclusion criteria
1. Patients with low grade ovarian carcinoma.
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.
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 | EUCTR2008-003439-18-NL |
| ClinicalTrials.gov | NCT00753545 |
| CCMO | NL27719.031.09 |