An Open Label, Single Arm, Multicentre Study of Lynparza (Olaparib) Capsules in Relapsed BRCA Mutated Ovarian Cancer Patients (ORZORA)

• Register: EUCTR
• Last refreshed on: 7 January 2019
• Main ID: EUCTR2015-000734-30-GB
• Date of registration: 27/03/2015
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: An Open Label, Single Arm, Multicentre Study of Lynparza (Olaparib) Capsules in Relapsed BRCA Mutated Ovarian Cancer Patients (ORZORA)
• Scientific title: An Open Label, Single Arm, Multicentre Study to Assess the Clinical Effectiveness and Safety of Lynparza (Olaparib) Capsules Maintenance Monotherapy in Platinum Sensitive Relapsed somatic or germline BRCA Mutated Ovarian Cancer Patients who are in Complete or Partial Response Following Platinum based Chemotherapy (ORZORA) - Astra Zeneca ORZORA D0816C00012
• Date of first enrolment: 10/07/2015
• Target sample size: 275
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000734-30
• 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): no Therapeutic use (Phase IV): yes

Countries of recruitment

Bulgaria, Canada, Czech Republic, Hungary, Italy, Poland, Spain, 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. Age 18 years or over
3. Documented germline or somatic mutation in BRCA1 or BRCA2 genes that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function) [Genetic counselling for patients with germline BRCA mutations should be performed according to local regulations] or Tumour BRCAwt status and documented qualifying mutation in any of 13 genes involved in the HRR pathway, excluding BRCA1 and BRCA2 (ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L), identified by the Lynparza HRR Assay in archival tumour tissue (i.e., BRCA-independent HRRm)
4. Patients with platinum sensitive relapsed high grade epithelial ovarian cancers (including primary peritoneal and/or fallopian tube cancer): Platinum sensitive disease is defined as disease progression =6 months after completion of their last dose of platinum based chemotherapy
5. Patients should have received at least 2 previous lines of platinum containing therapy prior to enrolment:
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) and no evidence of a rising CA-125, following completion of this chemotherapy course.
6. Patients must have normal organ and bone marrow function measured within 28 days of enrolment, as defined below:
Haemoglobin = 10.0 g/dL with no blood transfusions in the past 28 days
Absolute neutrophil count (ANC) = 1.5 x 109/L
Platelet count = 100 x 109/L
7. 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 ULN unless liver metastases are present in which case they must be = 5x ULN
8. Creatinine clearance > 50 ml/min (calculated)
9. Patients must be postmenopausal or have evidence of non-childbearing status for women of childbearing potential as defined in the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 138
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 137

Exclusion criteria:
1. Patients previously diagnosed with gBRCAm disease
2. Participation in another clinical study with an investigational product during the most recent chemotherapy course
3. Patients with a known hypersensitivity to olaparib or any of the excipients of the product
4. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) or major surgery within 3 weeks prior to olaparib treatment. Major surgery within 3 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
5. Persistent toxicities Common Terminology Criteria for Adverse Event (CTCAE) grade 2 caused by previous cancer therapy, excluding alopecia
6. Patients with myelodysplastic syndrome/acute myeloid leukaemia
7. Immuno-compromised patients e.g. Human Immunodeficiency Virus (HIV) requiring treatment or active Hepatitis B or C
8. 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
9. Patients considered to be at a high medical risk due to a serious, uncontrolled medical disorder, systemic disease or active, uncontrolled infection.
10. Currently pregnant (confirmed with a positive pregnancy test) or breastfeeding


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

Health Condition(s) or Problem(s) studied

BRCA or HRR+ Mutated Ovarian Cancer Patients
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)

Trade Name: Lynparza
Product Name: Lynparza
Product Code: AZD2281(KU-0059436)
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: olaparib
CAS Number: 763113-22-0
Current Sponsor code: AZD2281 (KU-0059436)
Other descriptive name: OLAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Main Objective: To assess the real world clinical effectiveness of olaparib maintenance monotherapy by investigator assessed progression free survival (PFS) according to modified Response Evaluation Criteria In Solid Tumours (RECIST) 1.1 in patients with sBRCAm ovarian cancer. To assess the real world clinical effectiveness of olaparib maintenance monotherapy by investigator assessed PFS according to RECIST 1.1 in patients with BRCAm ovarian cancer.

Secondary Objective: To assess the real world clinical effectiveness of olaparib maintenance
monotherapy in patients with BRCAm ovarian cancer and patients with sBRCAm ovarian cancer, by assessment of: - overall survival (OS), - time to investigator- assessed second progression (PFS2), or death. - time to first subsequent therapy or death (TFST), - time to second subsequent therapy or death (TSST) and - time to olaparib discontinuation or death (TDT) To assess and describe the following for patients with BRCAm ovarian cancer and patients with sBRCAm ovarian cancer. - quality of life (QoL) - patterns of routine clinical use of olaparib, the nature and patterns of AEs of nausea and
vomiting and their impact on QoL - safety and tolerability of olaparib
maintenance monotherapy To describe nausea/vomiting toxicity management patterns used in routine clinical practice.

Primary end point(s): PFS (Progression Free Survival) is defined as the time from enrolment until the date of objective radiological disease progression (assessed via RECIST 1.1) or death (by any cause in the absence of disease progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to disease progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable efficacy assessment. However, if the patient progresses or dies after two or more missed visits, the patient will be censored at the time of the latest evaluable assessment. Given the scheduled visit assessment scheme, two missing visits will equate to more than 26 weeks since the previous RECIST 1.1 assessment, allowing for early and late visits. If the patient has no evaluable visits or does not have a baseline assessment they will be censored at day 1 unless they die within two visits of baseline (25 weeks allowing for visit window).

The PFS time will always be derived based on scan/assessment dates not visit dates. Assessments/scans contributing towards a particular visit may be performed on different dates. The following rules will be applied:
• Date of progression will be determined based on the earliest of the assessment/scan dates of the component that triggered the progression.
• When censoring a patient for PFS the patient will be censored at the latest of the assessment/scan dates contributing to a particular overall visit assessment.

Overall visit assessments will be determined for each assessment (scheduled or unscheduled) and will contribute to the derivation of PFS.

Objective radiological progression is defined as at least a 20% increase in the sum of the diameters of the target lesions (compared to previous minimum sum) and an absolute increase of > 5 mm, or an overall non-target lesion assessment of progression or a new lesion.

Timepoint(s) of evaluation of this end point: Date of progression

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Overall Survival, TFST, TDT and TSST will be assessed from date of enrolment until the specific event or death.

Time from randomisation to second progression (PFS2) will be assessed every 12 weeks

Secondary end point(s): Overall Survival (OS)
Overall survival is defined as the time from the date of enrolment in the study until death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.
Time from enrolment to second progression (PFS2)
Time from enrolment to second progression is defined as the time from the date of enrolment to the earliest of the progression event subsequent to that used for the primary variable PFS or death. The date of second progression will be recorded by the investigator and defined according to local standard clinical practice and may involve any of objective radiological, symptomatic, CA-125 progression or death. Second progression status will be reviewed every 12 weeks following the progression event used for the primary variable PFS (the first progression) and status recorded. Patients alive and for whom a second disease progression has not been observed should be censored at the last time known to be alive and without a second disease progression, i.e. censored at the last assessment for progression date if the patient has not had a second progression or death).
Time to first subsequent anti-cancer therapy or death (TFST)
As a supportive summary to PFS, time to start of first subsequent anti-cancer therapy or death will be assessed. Time to first subsequent therapy or death is defined as the time from the date of enrolment to the earlier of first subsequent therapy start date, or death date. Any patient not known to have had a further subsequent therapy or death will be censored at the last known time to have not received subsequent anti-cancer therapy.
Time to study treatment discontinuation or death (TDT)
Time to study treatment discontinuation or death (TDT) will be assessed. TDT is defined as the time from the date of enrolment to the earlier of the date of study treatment discontinuation or death. Any patient not known to have died at the time of analysis and not known to have discontinued study treatment will be censored based on the last recorded date on which the patient was known to be alive.
Time to second subsequent chemotherapy or death (TSST)
As a supportive summary to PFS2, time to start of second subsequent chemotherapy or death will be assessed. Time to second subsequent chemotherapy or death is defined as the time from the date of enrolment to the earlier of the date of second subsequent chemotherapy start date, or death date. Any patient not known to have had a further second subsequent therapy or death will be censored at the last known time to have not received second subsequent chemotherapy.

Secondary ID(s)

D0816C00012

Source(s) of Monetary Support

AstraZeneca AB