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

Conditions

• Metastatic Triple Negative Breast Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - 130 Years

Healthy Volunteers

Not accepted

Interventions

• Olaparib Continuous (28-Day cycle) 300 mg BD. — DRUG
  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).
• Ceralasertib 160 mg OD + olaparib continuous 300 mg BD (28-day cycle). — DRUG
  Patients will be administered Ceralasertib OD at 160 mg from Day 1 to Day 7 (inclusive) of every 28-day cycle.
• Adavosertib 150 mg BD + olaparib 200 mg BD (21-day cycle). — DRUG
  Patients will be administered adavosertib BD at 150mg from Day 1 to Day 3 and Day 8 to Day 10.

Study Details

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.

Key Dates

Start date

Mar 7, 2018

Status verified

Feb 2026

Primary completion

Nov 13, 2020

Completion

Sep 4, 2026

Study Design

Enrollment

273 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Olaparib monotherapy
  All randomized patients will receive Olaparib monotherapy 300 mg twice daily (BD).
• Active Comparator: Olaparib+Ceralasertib
  All randomized patients will receive Olaparib 300 mg twice daily+Ceralasertib 160 mg once daily (OD).
• Active Comparator: Olaparib+adavosertib
  All randomized patients will receive Olaparib 200 mg BD +adavosertib 150 mg BD. Following the discontinuation of adavosertib+olaparib treatment arm on 18 April 2019, patients receiving treatment with adavosertib+olaparib treatment were offered the opportunity to continue treatment on olaparib monotherapy at the approved dose (300 mg bd).

Primary Outcome Measure

Progression-free Survival Per Stratum (BICR) [ Time Frame: Until date of first documented progression or censoring date or date of death from any cause, whichever came first (assessed up to 32 months) ]

Locations (20)

Find similar trials in Birmingham, AL