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To Assess Safety and Efficacy of Agents Targeting DNA Damage Repair With Olaparib Versus Olaparib Monotherapy.

NCT03330847 · Status: ACTIVE_NOT_RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 273

Last updated 2026-03-10

Study results available
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Summary

This study is to assess the efficacy and safety of olaparib monotherapy versus olaparib in combination with an inhibitor of ATR (Ataxia-Telangiectasia Mutated (ATM) and Rad3-related protein kinase (Ceralasertib \[AZD6738\]) and olaparib monotherapy versus olaparib in combination with an inhibitor of WEE1 (adavosertib \[AZD1775\]) in second or third line setting in patients with Triple-negative breast cancer (TNBC) prospectively stratified by presence/absence of qualifying tumour mutation in genes involved in the homologous recombination repair (HRR) pathway. Treatment arms are olaparib monotherapy, olaparib+ Ceralasertib and olaparib+adavosertib. The study subject population will be divided into Stratum A, Stratum B, and Stratum C. Due to the different schedules of administration of each of the treatment options as well as their different toxicity profiles, the study is not blinded. Study has two stage consent process- stage 1 consent (molecular screening for HRR defects) and stage 2 consent (main study). Patients with TNBC and with known qualifying BRCAm, non BRCAm HRRm and non HRRm status will be offered the option of consenting to the main part of the study within the 28-day screening period. Following the ISRC meeting on 17 April 2019 a recommendation was made to close the adavosertib+olaparib treatment arm across all biomarker strata. Patients receiving treatment with adavosertib+olaparib treatment were offered the opportunity to continue treatment on olaparib monotherapy at the approved dose (300 mg bd). Following the closure of this arm the total number of patients randomised will be lower (approximately 350 patients). Approximately 300 patients will be randomised (using randomisation ratio 1:1) to 2 ongoing treatment arms plus an additional 47 patients to a 3rd arm (olaparib+adavosertib) prior to the arm being discontinued.

Conditions

Interventions

DRUG

Olaparib Continuous (28-Day cycle) 300 mg BD.

Two (2) 150 mg olaparib tablets should be taken at the same time each day, approximately 12 hours apart with one glass of water (approximately 250 mL).

DRUG

Ceralasertib 160 mg OD + olaparib continuous 300 mg BD (28-day cycle).

Patients will be administered Ceralasertib OD at 160 mg from Day 1 to Day 7 (inclusive) of every 28-day cycle.

DRUG

Adavosertib 150 mg BD + olaparib 200 mg BD (21-day cycle).

Patients will be administered adavosertib BD at 150mg from Day 1 to Day 3 and Day 8 to Day 10.

Sponsors & Collaborators

Principal Investigators

  • Andrew Tutt, MB ChB PhD · Guy's Hospital, Great Maze Pond, London.

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Max Age
130 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2018-03-07
Primary Completion
2020-11-13
Completion
2026-09-04
FDA Drug
Yes

Countries

  • United States
  • Belgium
  • Canada
  • Czechia
  • France
  • Germany
  • Ireland
  • Italy
  • Netherlands
  • Poland
  • Portugal
  • South Korea
  • Spain
  • Taiwan
  • United Kingdom

Study Locations

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Entities

Diseases
Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03330847 on ClinicalTrials.gov