To assess the efficacy and safety of olaparib maintenance monotherapy in the treatment of ovarian cancer - ORZORA

Study identifier:D0816C00012

ClinicalTrials.gov identifier:NCT02476968

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official 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).

Medical condition

BRCA or HRR+ Mutated Ovarian Cancer Patients

Phase

Phase 4

Healthy volunteers

Study drug

Olaparib

Sex

Female

Actual Enrollment

181

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 28 Sept 2015

Primary Completion Date: 17 Apr 2020

Study Completion Date: 17 Dec 2021

Study design

Allocation: Non-randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Other

Verification:

Verified 01 Aug 2022 by AstraZeneca

Collaborators

Inclusion and 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.

The study will recruit approximately 250 patients with sBRCAm disease or gBRCAm disease, with the aim to accrue a minimum of 50 patients with sBRCAm disease. Patients with an unknown germline BRCA mutated status or gBRCAwt disease or previously identified as having a BRCAm disease by a tumour test will be considered for screening and will undergo, upon informed consent signature, central tumor and blood testing to determine their BRCA mutation status. In addition to central BRCA testing, patients screened for the study with unknown BRCA status or with known gBRCAwt status, for whom an adequate archival tumour tissue sample is available, will be tested for qualifying HRR gene alterations. Patients confirmed to carry a deleterious or suspected deleterious BRCA-independent genetic alteration in any of 13 genes involved in the Homologous Recombination Repair (HRR) pathway (HRRm cohort) will be allowed into an additional exploratory cohort (HRRm cohort). It is expected that approximately 25 patients will be included in the HRRm cohort before the target number of 250 patients with BRCAm disease is reached. Patients will be assigned olaparib capsules orally 400 mg twice daily. They should initiate olaparib treatment within 8 weeks after their last dose of platinum-containing chemotherapy (last dose is the day of the last infusion) and will be assessed every 4 weeks whilst on treatment. All patients will have clinical and objective radiological tumour assessments according to modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines at baseline and every 12 weeks relative to date of enrolment, until objective radiological disease progression as determined by the investigator. Patients could continue to receive olaparib for as long as determined by the investigator, until objective radiological disease progression or as long as in the investigator’s opinion they are benefiting from treatment in relation to other clinical assessments and they do not meet any other discontinuation criteria. Once a patient has discontinued olaparib she will be managed as per local clinical practice but will remain in the study and data will be collected on subsequent treatments, progression, overall survival and safety. For exploratory analysis purposes, patients will be asked to provide consent to: 1. Optional tumour samples at baseline and at disease progression 2. An optional blood sample only for patients with a confirmed sBRCAm or HRRm disease

No locations available

Arms	Assigned Interventions
Other: Olaparib Open Label Drug	Drug: Olaparib Olaparib Capsule – 50 mg. Olaparib capsules will be packed in high-density polyethylene (HDPE) bottles with child-resistant closures. Each bottle will contain 120 capsules and 4 bottles will be dispensed for a 4 weekly visit, with a 2 day overage. Patients will be administered olaparib capsules orally at a dose of 400 mg twice daily. Eight 50 mg olaparib capsules should be taken at the same time each day approximately 12 hours apart with approximately 240 mL of water. Other Name: Lynparza

Arms

Assigned Interventions

Other: Olaparib
Open Label Drug

Drug: Olaparib
Olaparib Capsule – 50 mg. Olaparib capsules will be packed in high-density polyethylene (HDPE) bottles with child-resistant closures. Each bottle will contain 120 capsules and 4 bottles will be dispensed for a 4 weekly visit, with a 2 day overage. Patients will be administered olaparib capsules orally at a dose of 400 mg twice daily. Eight 50 mg olaparib capsules should be taken at the same time each day approximately 12 hours apart with approximately 240 mL of water.

Other Name: Lynparza

Documents available

Redacted SAP
Download
Redacted CSP
Download
Synopsis_Primary
Download
Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Sandro Pignata

Istituto Nazionale Tumori Fondazione G. Pascale, 80131, Napoli, Italy