To Assess the Efficacy and Safety of Olaparib Maintenance Monotherapy in the Treatment of Ovarian Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 28 June 2021
• Main ID: NCT02476968
• Date of registration: 10/06/2015
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: To Assess the Efficacy and Safety of Olaparib Maintenance Monotherapy in the Treatment of Ovarian Cancer 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).
• Date of first enrolment: September 28, 2015
• Target sample size: 181
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02476968
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Other. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

Bulgaria, Canada, Croatia, Czech Republic, Czechia, Hungary, Israel, Italy, Poland, Portugal, Saudi Arabia, Spain, United Kingdom

Contacts

• Name: Sandro Pignata, Doctor of Medicine
• Affiliation: Istituto Nazionale Tumori Fondazione G. Pascale, 80131, Napoli, Italy

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.

Postmenopausal is defined as any of the following:

- Amenorrhoea for 1 year or more following cessation of exogenous hormonal treatments

- For women under 50 years old, luteinizing hormone (LH) and follicle stimulating
hormone (FSH) levels in the post-menopausal range

- Radiation-induced oophorectomy, with interval of 1 year or more since last menses

- Chemotherapy-induced menopause, with interval of 1 year or more since last menses

- Surgical sterilisation (bilateral oophorectomy or hysterectomy).

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: 18 Years
Age maximum: 130 Years
Gender: Female

Health Condition(s) or Problem(s) studied

BRCA or HRR+ Mutated Ovarian Cancer Patients

Intervention(s)

Drug: Olaparib

Primary Outcome(s)

Progression-Free Survival (PFS) [Time Frame: Tumour assessments at baseline then every 12 weeks relative to date of enrolment until RECIST 1.1-defined progression. Assessed until primary analysis DCO (up to maximum of 55 months).]

Secondary Outcome(s)

PFS2 or Death; Assessed at Final Analysis [Time Frame: Tumour assessments (and blood samples for CA-125, if applicable) at baseline then every 12 weeks relative to date of enrolment until second progression. Assessed until final analysis DCO (estimated up to approximately 6 years).]

TSST; Assessed at Final Analysis [Time Frame: From enrolment to second subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until final analysis DCO (estimated up to approximately 6 years).]

Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Scores Over Time [Time Frame: QoL questionnaires at baseline, Day 29 (Week 4), then every 12 weeks for 24 months or DCO for primary analysis, whichever came first. QoL questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose.]

OS; Assessed at Final Analysis [Time Frame: From baseline until death due to any cause. Assessed until final analysis DCO (estimated up to approximately 6 years).]

Overall Survival (OS); Assessed at Primary Analysis [Time Frame: From baseline until death due to any cause. Assessed until primary analysis DCO (up to maximum of 55 months).]

Time to First Subsequent Therapy (Treatment) or Death (TFST); Assessed at Primary Analysis [Time Frame: From enrolment to first subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until primary analysis DCO (up to maximum of 55 months).]

Change From Baseline in Functional Assessment of Cancer Therapy - Ovarian (FACT-O) Trial Outcome Index (TOI) Scores Over Time [Time Frame: QoL questionnaires at baseline, Day 29 (Week 4), then every 12 weeks for 24 months or DCO for primary analysis, whichever came first. QoL questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose.]

Time to Discontinuation of Treatment or Death (TDT) [Time Frame: From enrolment to study treatment discontinuation or death. Assessed until primary analysis DCO (up to maximum of 55 months).]

Change From Baseline in Functional Living Index-Emesis (FLIE) Questionnaire Total Scores Over Time [Time Frame: FLIE questionnaires at baseline, weekly until Day 29 (Week 4), then every 12 weeks for 24 months or DCO for primary analysis, whichever came first. FLIE questionnaires also collected at discontinuation of study treatment visit and 30 days post last dose.]

TFST; Assessed at Final Analysis [Time Frame: From enrolment to first subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until final analysis DCO (estimated up to approximately 6 years).]

Time to Second Progression (PFS2) or Death; Assessed at Primary Analysis [Time Frame: Tumour assessments (and blood samples for CA-125, if applicable) at baseline then every 12 weeks relative to date of enrolment until second progression. Assessed until primary analysis DCO (up to maximum of 55 months).]

Time to Second Subsequent Therapy (Treatment) or Death (TSST); Assessed at Primary Analysis [Time Frame: From enrolment to second subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until primary analysis DCO (up to maximum of 55 months).]

Secondary ID(s)

D0816C00012

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 18/06/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02476968