Clinical Trial: NCT03330847
To Assess Safety and Efficacy of Agents Targeting DNA Damage Repair With Olaparib Versus Olaparib Monotherapy.
Status:
ACTIVE NOT RECRUITINGPhase:
Phase 2| Lead Sponsor: | AstraZeneca |
| Information Provided By: | AstraZeneca |
| Last Update Posted: | 2026-10-14 |
Study Overview
Brief 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.
Official Title
Conditions
Intervention / Treatment
- Drug: Olaparib Continuous (28-Day cycle) 300 mg BD.
- Drug: Ceralasertib 160 mg OD + olaparib continuous 300 mg BD (28-day cycle).
- Drug: Adavosertib 150 mg BD + olaparib 200 mg BD (21-day cycle).
Other Study ID Numbers
- D5336C00001
- 2017-002361-22
- 2017
Start Date (Actual)
Primary Completion Date (Actual)
Study Completion Date (Estimated)
Enrollment (Actual)
Study Type
Phase
| Lead Sponsor: | AstraZeneca |
| Information Provided By: | AstraZeneca |
| Last Update Posted: | 2026-10-14 |
Study Overview
Brief 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.
Official Title
Conditions
Intervention / Treatment
- Drug: Olaparib Continuous (28-Day cycle) 300 mg BD.
- Drug: Ceralasertib 160 mg OD + olaparib continuous 300 mg BD (28-day cycle).
- Drug: Adavosertib 150 mg BD + olaparib 200 mg BD (21-day cycle).
Other Study ID Numbers
- D5336C00001
- 2017-002361-22
- 2017