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

Phase 1

Conditions: BRCA or HRR+ Mutated Ovarian Cancer Patients
Therapeutic area: Diseases [C] - Cancer [C04]
MedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Registration Number: EUCTR2015-000734-30-GB

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Female

Target Recruitment: 275

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