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

NCT02476968 | Completed Phase 4 Results

• 1 other identifier: D0816C00012
• Study Type: interventional
• Target: 181
• Locations: 8 countries
• Sites: 58

Brief Summary

This is a prospective, open-label, single arm, multi-center study to assess the real world clinical effectiveness and safety of olaparib maintenance monotherapy as the capsule formulation (in line with the EU approved prescribing information) and will be conducted in platinum-sensitive relapsed high grade epithelial ovarian cancer patients (including patients with primary peritoneal and / or fallopian tube cancer) who carry germline or somatic BRCA mutations (documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious \[known or predicted to be detrimental/lead to loss of function\]).

Conditions

BRCA or HRR+ Mutated Ovarian Cancer Patients

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  To assess the real-world clinical effectiveness of olaparib maintenance monotherapy in patients with BRCAm and sBRCAm ovarian cancer by assessment of PFS. The PFS was defined as the time from the date of enrolment until date of objective radiological disease progression (assessed by the Investigator via Response Evaluation Criteria in Solid Tumors, version 1.1 \[RECIST 1.1\]), or death (by any cause in absence of disease progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to disease progression. Objective progression was 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 millimeters, or an overall non-target lesion assessment of progression or a new lesion. The data cut-off (DCO) for the primary analysis of the study occurred after approximately 60% maturity of PFS in the sBRCAm and all BRCAm patient populations.

  Tumour assessments at baseline then every 12 weeks relative to date of enrolment until RECIST 1.1-defined progression. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months).

Secondary Outcomes (12)

• Overall Survival (OS); Assessed at Primary Analysis

  From baseline until death due to any cause. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months).

• Time to Second Progression (PFS2) or Death; Assessed at Primary Analysis

  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 of 17 April 2020 (up to maximum of 55 months).

• Time to First Subsequent Therapy (Treatment) or Death (TFST); Assessed at Primary Analysis

  From enrolment to first subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months).

• Time to Second Subsequent Therapy (Treatment) or Death (TSST); Assessed at Primary Analysis

  From enrolment to second subsequent therapy or death. Assessed every 12 weeks following treatment discontinuation. Assessed until primary analysis DCO of 17 April 2020 (up to maximum of 55 months).

• Time to Discontinuation of Treatment or Death (TDT)

  From enrolment to study treatment discontinuation or death (up to maximum of 6 years).

Study Arms (1)

Olaparib

OTHER

Open Label Drug

Drug: Olaparib

Interventions

Olaparib DRUG

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.

Also known as: Lynparza

Olaparib

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures
• Age 18 years or over
• 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)
• 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
• 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.
• 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
• 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
• Creatinine clearance \> 50 ml/min (calculated)
• Patients must be postmenopausal or have evidence of non-childbearing status for women of childbearing potential.
• Postmenopausal is defined as any of the following:

You may not qualify if:

• Patients previously diagnosed with gBRCAm disease
• Participation in another clinical study with an investigational product during the most recent chemotherapy course
• Patients with a known hypersensitivity to olaparib or any of the excipients of the product
• 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
• Persistent toxicities Common Terminology Criteria for Adverse Event (CTCAE) grade 2 caused by previous cancer therapy, excluding alopecia
• Patients with myelodysplastic syndrome/acute myeloid leukaemia
• Immuno-compromised patients e.g., Human Immunodeficiency Virus (HIV) requiring treatment or active Hepatitis B or C
• 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
• Patients considered to be at a high medical risk due to a serious, uncontrolled medical disorder, systemic disease or active, uncontrolled infection
• Currently pregnant (confirmed with a positive pregnancy test) or breastfeeding.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (58)

Research Site

Plovdiv, 4000, Bulgaria

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Plovdiv, 4004, Bulgaria

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Sofia, 1303, Bulgaria

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Sofia, 1330, Bulgaria

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Sofia, 1407, Bulgaria

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Sofia, 1756, Bulgaria

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Varna, 9010, Bulgaria

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Calgary, Alberta, T2N 4N2, Canada

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Halifax, Nova Scotia, B3H 2E2, Canada

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London, Ontario, N6A 4L6, Canada

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Toronto, Ontario, M5G 1X6, Canada

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Montreal, Quebec, H2X 0A9, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Brno, 625 00, Czechia

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Brno, 656 53, Czechia

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Nový Jičín, 741 01, Czechia

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Olomouc, 775 20, Czechia

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Ostrava, 708 52, Czechia

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Prague, 128 08, Czechia

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Prague, 15000, Czechia

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Budapest, 1032, Hungary

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Budapest, 1062, Hungary

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Budapest, 1122, Hungary

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Debrecen, 4032, Hungary

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Kecskemét, 6000, Hungary

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Nyíregyháza, 4400, Hungary

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Bari, 70124, Italy

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Milan, 20141, Italy

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Napoli, 80131, Italy

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Perugia, 06132, Italy

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Bialystok, 15-027, Poland

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Gdansk, 80-402, Poland

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Kielce, 25-734, Poland

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Poznan, 60-569, Poland

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Poznan, Poland

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Badalona, 08916, Spain

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Barcelona, 08025, Spain

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Burgos, 09006, Spain

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L'Hospitalet de Llobregat, 08908, Spain

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Madrid, 28040, Spain

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Madrid, 28041, Spain

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San Cristóbal de La Laguna, 38320, Spain

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Seville, 41009, Spain

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Valencia, 46010, Spain

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Valencia, 46026, Spain

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Zaragoza, 50009, Spain

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Belfast, BT9 7AB, United Kingdom

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Birmingham, B18 7QH, United Kingdom

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Cardiff, CF14 2TL, United Kingdom

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Glasgow, G12 OYN, United Kingdom

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Leeds, LS9 7TF, United Kingdom

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London, SE1 9RT, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

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Newcastle upon Tyne, NE7 7DN, United Kingdom

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Oxford, OX3 7LJ, United Kingdom

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Swansea, SA2 8QA, United Kingdom

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Taunton, TA1 5DA, United Kingdom

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Related Links

• Redacted SAP
• Redacted CSP
• Synopsis\_Primary
• Synopsis

MeSH Terms

Interventions

olaparib

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Sandro Pignata, Doctor of Medicine

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2015
• First Posted: June 22, 2015
• Study Start: September 28, 2015
• Primary Completion: April 17, 2020
• Study Completion: December 17, 2021
• Last Updated: September 10, 2022
• Results First Posted: June 18, 2021

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

BU (7); GB (12); ES (11); CA (6); CZ (7); PL (5); IT (4); HU (6)