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

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2017-002767-17-NL
• Date of registration: 21/12/2017
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: 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
• Scientific title: 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. - OPINION
• Date of first enrolment: 21/12/2017
• Target sample size: 250
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002767-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Bulgaria, Canada, Czech Republic, Denmark, Finland, Israel, Italy, Netherlands, Norway, Poland, Portugal, Romania, Slovenia, Spain, Sweden, Switzerland, United Kingdom

Contacts

• Name: Information center
• Affiliation: AstraZeneca

• Name: Information center
• Affiliation: AstraZeneca

Key inclusion & exclusion criteria

Inclusion criteria:
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 ovarian 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 or oxaliplatin 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 (e.g. carboplatin or, cisplatin or oxaliplatin) 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 lis
Exclusion criteria:
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 hormonal therapy, 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 unless curatively treated with no evidence of disease for =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.
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

Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Non Germline BRCA Mutated Ovarian Cancer
MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: olaparib
Product Code: AZD2281
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: olaparib
CAS Number: 763113-22-0
Current Sponsor code: AZD2281
Other descriptive name: OLAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: olaparib
Product Code: AZD2281
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: olaparib
CAS Number: 763113-22-0
Current Sponsor code: AZD2281
Other descriptive name: OLAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: At visit 4 and on the first day of each 8 week visit period, relative to the date of the first olaparib dose, for the first 12 months on treatment, and subsequently each 12-week visit period, until the earlier of progression, death or end of study for up to 36months.

Secondary Objective: Det. efficacy of olaparib maintenance monotherapy in non gBRCAm PSR ovarian cancer by assessment of time to first subsequent therapy or death (TFST)
Det. efficacy of olaparib maintenance monotherapy in non gBRCAm PSR ovarian cancer by assessment of time to treatment discontinuation or death (TDT)
Det. efficacy by PFS of olaparib maintenance in non gBRCAm PSR ovarian cancer according to tumour HRD status using the Myriad myChoice plus HRD test
Det. efficacy of olaparib maintenance monotherapy in non gBRCAm PSR ovarian cancer by assessment of hemotherapy-free interval (CT-FI)
Det. the OS of non-gBRCAm PSR ovarian cancer patients treated with olaparib maintenance monotherapy
Investigate the HRQoL of non gBRCAm PSR ovarian cancer patients treated with olaparib maintenance monotherapy as assessed by the trial outcome index (TOI) of the FACT-O
Assess the safety and tolerability of olaparib maintenance monotherapy in patients with non gBRCAm PSR ovarian cancer

Main Objective: To determine the efficacy by progression-free survival (PFS) (investigator-recorded assessments according to modified Response Evaluation Criteria In Solid Tumors [RECIST v1.1]) of olaparib maintenance monotherapy in non gBRCAm platinum sensitive relapsed (PSR) ovarian cancer

Primary end point(s): PFS: Time from date of first dose until the date of objective radiological disease progression according to modified RECIST 1.1 or death (by any cause in the absence of progression)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: (1) (2) visit 2, 3, 4 and every tumor assessment visit (TAV), at study drug discontinuation,at 30 days post last dose, every 12 weeks during long term FUP
(3) visit 4 and every 8 week for the first 12 months, each 12 week until earlier progression, death or EOS (4) screening, Visit 2, 3, 4 and subsequent TAV, Visit 5 and subsequent safety visits (SV) (at day 85 and then every 8 weeks), until 30 days after last dose and then every 12 weeks until EOS
(5) OS : when 135 death events recorded (54% maturity) expected at aprox 36 months.
(6) (7)visit 2, 3, 4 and at every TAV until progression, at discontinuation of study drug visit and at 30 days post last dose
(7) screening, Visit 2, 3, 4 and subsequent TAV , Visit 5 and subsequent SV, until 30 days after last dose of study drug

Secondary end point(s): (1) - TFST: Time from date of first dose to date of first subsequent treatment commencement or death due to any cause if this occurs before commencement of first subsequent treatment
(2) - TDT: Time from date of first dose to date of study drug discontinuation or death due to any cause if this occurs before study drug discontinuation
(3) - PFS in the following subgroups:
1. Somatic BRCA mutated and HRD scar positive;
2. HRD scar positive, non-BRCA mutated;
3. HRD scar negative, non-BRCA mutated
(4) - CT-FI: Time from the date of the last dose of platinum chemotherapy prior to olaparib maintenance therapy until the date of initiation of the next anticancer therapy
(5)- OS: Time from the date of first dose of olaparib to date of death from any cause
(6) - Proportion of patients with any improvement from baseline in TOI score at any point during the treatment period
(7) - Proportion of patients with a 10 point deterioration from baseline in TOI score at any point during the treatment period
(8) - AE/SAE. Collection of clinical chemistry/haematology parameters.

Secondary ID(s)

2017-002767-17-SI

D0816C00020

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date:
Contact: