GOG 3004: A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Olaparib Maintenance Monotherapy in Patients with BRCA Mutated Advanced (FIGO Stage III-IV) Ovarian Cancer following First Line Platinum Based Chemotherapy.

Summary

This is a phase iii, randomised, double-blind, placebo-controlled, multi-centre study to assess the efficacy of olaparib maintenance monotherapy in high risk advanced ovarian cancer patients (including patients with primary peritoneal and / or fallopian tube cancer) with BRCa mutations [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) who have responded following first line platinum based chemotherapy.

Patients will be randomised in a 2:1 ratio to the treatments as specified below:
* olaparib tablets p.o. 300mg twice daily.
* placebo tablets p.o. twice daily.

Randomisation will be stratified by:
* response to first line platinum chemotherapy (clinical complete response or partial
response)

Patients will be randomised within 8 weeks after their last dose of chemotherapy (last dose is the day of the last infusion).

approximately 344 patients will be randomised using an interactive Voice Response System /
interactive Web Response System (iVR/iWR system) in a 2:1 ratio to the treatments as
specified below:
* olaparib tablets p.o. 300 mg twice daily
* Placebo tablets p.o. twice daily

Participant Eligibility

Patients that already know they have a mutation in BRCA1 or BRCA2 gene that is predicted
to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of
function) must fulfil all of the criteria below. Patients that do not know their mutation status,
and who are being considered for this trial should be identified early so that the appropriate
BRCA mutation screening procedures can be put in place in a timely manner. For patients
that do not know their BRCA mutation status they must fulfil all of the criteria marked with an
asterisk below prior to BRCA mutation testing being carried out. All inclusion criteria will
then be assessed following confirmation that they harbour an appropriate BRCA mutation.
For inclusion in the study patients should fulfil the following criteria (any asterisked* are also
required for pre randomisation Myriad gBRCA status sample to determine study eligibility).
Any patient that fulfils the eligibility criteria for the BRCA test, are required to have their
eligibility assessed again prior to randomisation.
*Provision of informed consent prior to any study specific procedures.
1. *Patients must be >=18 years of age.
2. *Female patients with newly diagnosed, histologically confirmed, high risk
advanced (FIGO stage III x IV) BRCA mutated high grade serous or high grade
endometriod (based on local histopathological findings) ovarian cancer, primary
peritoneal cancer and / or fallopian-tube cancer who have completed first line
platinum based chemotherapy (intravenous or intraperitoneal).
3. * Stage III patients must have had one attempt at optimal debulking surgery
(upfront or interval debulking). Stage IV patients must have had either a biopsy
and/or upfront or interval debulking surgery.
4. 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)
5. *Patients who have completed first line platinum (carboplatin or cisplatin),
containing therapy (intravenous or intraperitoneal) prior to randomisation:
[?] Patients must have, in the opinion of the investigator, clinical complete
response or partial response and have no clinical evidence of disease
progression on the post-treatment scan or a rising CA-125 level, following
completion of this chemotherapy course. Patients with stable disease on the
post-treatment scan at completion of first line platinum-containing therapy are
not eligble for the study.
[?] [?]Response[Single Quote] is used throughout the protocol and refers to patients being, in the
opinion of the investigator, in clinical complete response or partial response on
the post-treatment scan. Clinical complete response is defined as no evidence of
RECIST measurable disease on the post-treatment scan and a normal CA-125.
Partial response is defined as >=30% reduction in tumor volume demonstrated
from the start to finish of chemotherapy OR no evidence of RECIST
measurable disease on the post-treatment scan with a CA-125 which has not
decreased to within the normal range.
[?] Platinum based chemotherapy course must have consisted of a minimum of 6
treatment cycles and a maximum of 9, however if platinum based therapy must
be discontinued early as a result of toxicities specifically related to the platinum
regimen, patients must have received a minimum of 4 cycles of the platinum
regimen.
[?] *Patients must not have received bevacizumab during their first line course of
treatment, either in combination or as maintenance therapy following
combination therapy.
[?] Patients must not have received an investigational agent during their first line
course of chemotherapy
[?] *Patients must be randomised within 8 weeks after 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 less than or equal to the upper limit of normal (ULN) the
patient is eligible to be randomised 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 first. 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 prior to administration of study treatment as defined below:
[?] Haemoglobin >= 10.0 g/dL with no blood transfusion in the past 28 days
[?] Absolute neutrophil count (ANC) >= 1.5 x 109/L
[?] Platelet count >= 100 x 109/L
[?] Total bilirubin <= 1.5 x institutional upper limit of normal (ULN)
[?] Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase
(SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate
Transaminase (SGPT)) <= 2.5 x institutional upper limit of normal unless liver
metastases are present in which case they must be <= 5x ULN
[?] Serum creatinine <= 1.5 x institutional ULN
8. *Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (see
Appendix D).
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 prior to Myriad BRCA test during
screening part 1, within 28 days of study treatment and confirmed prior to treatment
on day 1.
Postmenopausal is defined as:
[?] Amenorrheic for 1 year or more following cessation of exogenous hormonal
treatments
[?] Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in
the post menopausal range for women under 50
[?] radiation-induced oophorectomy with last menses >1 year ago
[?] chemotherapy-induced menopause with >1 year interval since last menses
[?] surgical sterilisation (bilateral oophorectomy or hysterectomy)
11. *Patients is willing and able to comply with the protocol for the duration of the
study including undergoing treatment and scheduled visits and examinations.
12. *Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary
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.
For inclusion in i) the optional exploratory genetic research and ii) the optional biomarker
research, patients must fulfil the following criteria:
[?] Provision of informed consent for genetic research
[?] Provision of informed consent for biomarker research
If a patient declines to participate in the optional exploratory genetic research or the optional
biomarker research, there will be no penalty or loss of benefit to the patient. The patient will
not be excluded from other aspects of the study.