Multicentre Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed Non gBRCAm Ovarian Cancer Patients (OPINION)
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|ClinicalTrials.gov Identifier: NCT03402841|
Recruitment Status : Active, not recruiting
First Posted : January 18, 2018
Last Update Posted : October 14, 2019
|Condition or disease||Intervention/treatment||Phase|
|Non-Germline BRCA Mutated Ovarian Cancer||Drug: Olaparib||Phase 3|
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|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Single arm study|
|Masking:||None (Open Label)|
|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|
|Estimated Primary Completion Date :||July 19, 2020|
|Estimated Study Completion Date :||January 4, 2021|
Olaparib will be supplied as film-coated tablets containing 150 mg or 100 mg of olaparib.
Patients will be administered olaparib orally twice daily (bid) at 300 mg.
300 mg twice daily - oral
Other Name: Lynparza
- Progression-free survival (PFS) [ Time Frame: Visit 1, 4 and on the first day of each 8 week visit period, relative to the date of the 1st olaparib dose, for the first 12 months on treatment, and then each 12-week visit period, until the earlier of progression, death or EOS for up to 30 months. ]Time from date of first dose of olaparib to the date of objective radiological disease progression according to investigator assessment via RECIST 1.1 or death (by any cause in the absence of progression)
- Time to first subsequent therapy or death (TFST) [ Time Frame: Visit 2, visit 3, visit 4 and then at every tumour assessment visit. TFST only: at discontinuation of study treatment visit, at 30 days post last dose and every 12 weeks during long term follow-up (for up to 30 months). ]Time from date of first dose to date of first subsequent treatment commencement or death due to any cause if this occurs before commencement of first subsequent treatment.
- Time to treatment discontinuation or death (TDT) [ Time Frame: Visit 2, visit 3, visit 4 and then at every tumour assessment visit. TFST only: at discontinuation of study treatment visit, at 30 days post last dose and every 12 weeks during long term follow-up (for up to 30 months). ]Time from date of first dose to date of study drug discontinuation or death due to any cause if this occurs before study drug discontinuation.
- PFS in the following subgroups: 1. Somatic BRCA mutated and HRD scar positive; 2. HRD scar positive, non-BRCA mutated; 3. HRD scar negative, non-BRCA mutated [ Time Frame: Visit 1, 4 and every 8 week for the first 12 months, and each 12 week until earlier progression, death or EOS for up to 30 months. ]Time from date of first dose of olaparib to the date of objective radiological disease progression according to investigator assessment via RECIST 1.1 or death (by any cause in the absence of progression)
- Chemotherapy-free interval (CT_FI) [ Time Frame: At Screening, Visit 2, 3, 4 and subsequent tumor assessment visits, Visit 5 and subsequent safety visits until 30 days after last dose and then every 12 weeks until EOS (for up to 30 months) ]Time from the date of the last dose of platinum chemotherapy prior to olaparib maintenance therapy until the date of the initiation of the next anticancer therapy .
- Trial outcome index (TOI) [ Time Frame: At baseline, visit 3, visit 4 and then at every tumor assessment visit until progression, at discontinuation of study treatment visit and at 30 days post last dose. ]Proportion of patients with any improvement from baseline in TOI score.
- AEs/SAEs [ Time Frame: Screening, Visit 2, 3, 4 and subsequent Tumor Assessment Visit, Visit 5 and subsequent Safety Visit, until 30 days after last dose of study drug. ]Will be assessed in terms of AEs, deaths and laboratory data.
- Overall Survival (OS) [ Time Frame: Visit 1, 4, first of each 8 week visit period relative to the data of first olaparib dose, for the first 12 months on threatment and then each 12 week visit period, until death or EOS for up to 30 months. ]Time from the date of first dose of olaparib to date of death from any cause
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03402841
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|Study Director:||Chris Wilks||AstraZeneca|