Chemo-free BRCA-targeted Neoadjuvant Strategy

Phase 2

Withdrawn

• Conditions: BRCA2 Mutation; TNBC - Triple-Negative Breast Cancer; BRCA1 Mutation
• Interventions: Drug: olaparib; Drug: Durvalumab

• Registration Number: NCT05209529
• Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary

This is a multicenter randomized phase ll clinical trial to evaluate the pathological complete response (pCR) in the tumour burden (primary and lymph nodes) with olaparib alone or in the olaparib and durvalumab arm in TNBC patients candidate for neoadjuvant strategy showing a t/gBRCAmut or BRCAness/HRD profile.

Detailed Description

Eligible patients will be registered for central testing of BRCA mutatinal status and HRD/BRCAness profile with central review of ER, PgR, TILs and PD-L1.

Eligible patients will be randomly assigned to either olparib or olaparib and durvalumab (=neoadjuvant treatment) in a 1:1 ratio. The treatment duration in both arms will last 16 weeks and both treatments are considered as experimental treatments in this study.

After completion of neoadjuvant systemic treatment, patients will undergo surgery and followed-up for 2 years after investigational drug discontinuation. After surgery, adjuvant treatment will be left at the investigator's decision.

Study Timeline

• Study First Submitted: 2022-01-12
• Study First Submitted QC: 2022-01-12
• Study First Posted: 2022-01-26
• Status Verified: 2024-02
• Study Start: 2024-02-01
• Last Update Submitted: 2024-02-21
• Last Update Posted: 2024-02-23
• Primary Completion: 2028-09-06
• Study Completion: 2030-07-18

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Olaparib	olaparib	Olaparib treatment for a total of 16 weeks
Olaparib and durvalumab	olaparib	Olaparib and durvalumab treatment for a total of 16 weeks
Olaparib and durvalumab	Durvalumab	Olaparib and durvalumab treatment for a total of 16 weeks

Primary Outcome Measures

Name	Time	Method
rate of pathological complete response (pCR) at the time of surgery	5 years from first patient in	pCR is defined as the absence of invasive residual disease in the breast and in the axillary lymph nodes (ypT0/is ypN0).

Secondary Outcome Measures

Name	Time	Method
Treatment response rate according to RECIST v1.1	7.5 years from first patient in
Breast conservation rate	7.5 years from first patient in
Other pathological response	7.5 years from first patient in	Residual cancer burden score (RCB), defined on the specimen collected at the time of surgery
Probability of being event-free at 2 years	7.5 years from first patient in	events considered being disease progression on neoadjuvant therapy, any event precluding surgery, locoregional recurrence, distant recurrence, second primary invasive cancer (breast and non-breast origin) and death from any cause
Global health status/QoL score	7.5 years from first patient in	score according to EORTC QLQ-C30 questionnaire
2-year overall survival (OS) rate	7.5 years from first patient in	OS is defined as date of randomization to the date of death, whatever comes first
Surgery rate	7.5 years from first patient in
Safety	7.5 years from first patient in	Rate of Adverse events not related directly with the surgical procedure (NCI-CTCAE Version 5.0) Rate of Post-operative complications (Clavien-Dindo Classification of Surgical Complications)
Score on the Systemic side effects scale	7.5 years from first patient in	according to the modified QLQ-BR45 (IL170) questionnaire