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Clinical trial

Multicentre Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed Non gBRCAm Ovarian Cancer Patients (OPINION)

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Last updated:9th Feb 2021
Status: Active, not recruiting
Identifier: NCT03402841
Multicentre Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed Non gBRCAm Ovarian Cancer Patients (OPINION)

Brief Summary:

The purpose of the study is to assess the efficacy and safety of single-agent olaparib as a maintenance treatment in patients with relapsed High Grade Serous Ovarian Cancer (including patients with primary peritoneal and/or fallopian tube cancer) or high grade endometrioid cancer who do not have known deleterious or suspected deleterious germline BRCA mutations (non-gBRCAm) and who had responded following platinum based chemotherapy

Detailed Description:
Maintenance monotherapy with the potent polyadenosine 5'diphosphoribose [Poly (ADP-ribose)] polymerisation (PARP) inhibitor (PARPi) olaparib will significantly prolong progression-free survival (PFS) in platinum sensitive relapsed non-germline breast cancer susceptibility gene (BRCA) mutated ovarian cancer patients who are in complete or partial response following platinum based chemotherapy.

Olaparib is a potent PARPi (PARP-1, -2 and -3) that is being developed as an oral therapy, both as a monotherapy (including maintenance) and for combination with chemotherapy and other anticancer agents. PARP inhibition is a novel approach to targeting tumours with deficiencies in DNA repair mechanisms. PARP enzymes are essential for repairing DNA single strand breaks (SSBs). Inhibiting PARP enzymes leads to the persistence of SSBs, which are then converted to the more serious DNA double strand breaks (DSBs) during the process of DNA replication. During the process of cell division, DSBs can be efficiently repaired in normal cells by homologous recombination (HR) repair. Tumours with HR deficiencies (HRDs), such as ovarian cancers in patients with BRCA1/2 mutations, cannot accurately repair the DNA damage, which may become lethal to cells as it accumulates. In such tumour types, olaparib may offer a potentially efficacious and less toxic cancer treatment compared with currently available chemotherapy regimens.

While multiple randomized controlled trials (RCTs) have demonstrated that platinum sensitive BRCAm patients have profound response to maintenance treatment with PARP inhibitors, PARP inhibitors target cells with homologous recombination deficiency (HRD), of which BRCA mutation is only one type. Consistent with the mechanism of action of PARP inhibition, response has also been seen in multiple RCTs in patients who are platinum sensitive but whose tumours do not harbor BRCA mutations. Presumably these responders have defects in other components of HRR pathways, though currently available diagnostic technology is not adequate to reliably identify the full spectrum of HRR deficiencies. Instead, these data support the hypothesis that platinum sensitivity itself is a clinical selection factor for HRD.

Study Type: Interventional (Clinical Trial)
Actual Enrollment: 279 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single arm study
Masking: None (Open Label)
Masking Description: Open
Primary Purpose: Treatment
Official Title: A Phase IIIb, Single-arm, Open-label Multicentre Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed Non-Germline BRCA Mutated Ovarian Cancer Patients Who Are in Complete or Partial Response Following Platinum Based Chemotherapy
Actual Study Start Date: January 30, 2018
Actual Primary Completion Date: October 2, 2020
Estimated Study Completion Date: April 4, 2021

- Experimental: Olaparib

Category Value
Study type(s) Interventional
Expected enrolment 279
Actual Study start date 30 January 2018
Estimated Study Completion Date 04 April 2021

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