Substantially Improving the Cure Rate of High-risk BRCA1-like Breast Cancer

NCT02810743 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: M16BRC
• Study Type: interventional
• Target: 174
• Locations: 2 countries
• Sites: 11

Brief Summary

Investigator-initiated, international, multicentre, randomized, open-label, (neo)adjuvant phase III study in target population (stage III, HER2-negative, BRCA1-like breast cancer patients) comparing optimized standard-dose chemotherapy with intensified, alkylating chemotherapy with stem cell rescue.

Conditions

Breast Cancer

Keywords

Stage III; HER2 negative; homologous recombination deficiency (HRD)

Outcome Measures

Primary Outcomes (1)

• Overall survival in all patients

  time from randomization to death from any cause in all patients

  assessed up to 120 months

Secondary Outcomes (7)

• Overall survival in patients without a germline BRCA1/2 mutation

  assessed up to 120 months

• Recurrence free interval in all patients

  assessed up to 120 months

• Recurrence free interval in patients with an HR impaired tumor

  assessed up to 120 months

• Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03

  up to 30 days after end of treatment

• cost-effectiveness measured by costs per quality-adjusted life years (QALYs)

  assessed up to 120 months

Study Arms (2)

ddAC-CP-Olaparib

ACTIVE COMPARATOR

ddAC; doxorubicin 60 mg/m² as an i.v. bolus and cyclophosphamide 600 mg/m² as an i.v. bolus on day 1 every 2 weeks ddAC must be supported with prophylactic pegfilgrastim 6 mg s.c. given 24-48 hours after completion of administration of EVERY chemotherapy cycle CP; carboplatin/paclitaxel (CP) consisting of carboplatin (AUC 6) on day 1 and paclitaxel (80 mg/m2) on day 1,8 and 15 of a 21 days cycle. In total 4 courses of CP will be administered. Olaparib will be administered in Dutch centers only, as monotherapy for one year at a dose of 300 mg BID, starting 3 weeks after adjuvant radiotherapy, or, if radiotherapy is not indicated, 3-5 weeks after the last CP cycle. Patients without a (near) pCR will receive adjuvant capecitabine at a starting dose of 1000-1250 mg/m2, twice a day, on days 1-14 every 3 weeks for eight cycles.

Drug: ddAC-CP-Olaparib

ddAC-mini CTC

ACTIVE COMPARATOR

ddAC; doxorubicin 60 mg/m² as an i.v. bolus and cyclophosphamide 600 mg/m² as an i.v. bolus on day 1 every 2 weeks ddAC must be supported with prophylactic pegfilgrastim 6 mg s.c. given 24-48 hours after completion of administration of EVERY chemotherapy cycle intensified alkylating 'mini' CTC (2x) cyclophosphamide 3000 mg/m2 day 1 mesna 500 mg (push) + 2000 mg in 24 hours day 1 carboplatin (400 mg/m2; (or AUC=5 in patients with a calculated creatinine-clearance of \<100 ml/min)) days 1,2 thiotepa 250 mg/m2 day 2 Patients without a (near) pCR will receive adjuvant capecitabine at a starting dose of 1000-1250 mg/m2, twice a day, on days 1-14 every 3 weeks for eight cycles.

Drug: ddAC-mini CTC

Interventions

ddAC-CP-Olaparib DRUG

ddAC-CP-Olaparib

ddAC-CP-Olaparib

ddAC-mini CTC DRUG

ddAC - mini CTC

ddAC-mini CTC

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women and men with stage III adenocarcinoma of the breast harboring signs of a breast cancer with features of homologous recombination deficiency (HRD)
• Age of 18-65 years
• The tumor must be HER2-negative
• Treatment must start within 8 weeks after the last surgical resection
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

You may not qualify if:

• Previous radiation therapy
• Previous chemotherapy
• Any previous treatment with a PARP-inhibitor, including olaparib
• Pre-existing neuropathy from any cause in excess of Grade 1
• Chronic concomitant use of known strong or moderate CYP3A inducers

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead

Study Sites (11)

Institut Paoli Calmettes

Marseille, 13009, France

Location

Hopital Tenon, University Marie-Curie

Paris, France

Location

Medical spectrum Twente

Enschede, Overijssel, 7500 KA, Netherlands

Location

Antoni van Leeuwenhoek

Amsterdam, 1066 CX, Netherlands

Location

AZVU

Amsterdam, 1081 HV, Netherlands

Location

University Medical Center Groningen

Groningen, Netherlands

Location

LUMC

Leiden, 2333 ZA, Netherlands

Location

Maastricht University Medical Center

Maastricht, Netherlands

Location

Radboud UMC

Nijmegen, 6225GA, Netherlands

Location

Erasmus Medical Center Cancer Institute

Rotterdam, 3015CE, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584CX, Netherlands

Location

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Sabine Linn, Prof. MD

  NKI-AvL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2016
• First Posted: June 23, 2016
• Study Start: January 25, 2017
• Primary Completion: July 18, 2024
• Study Completion (Estimated): December 1, 2033
• Last Updated: November 26, 2025

Record last verified: 2025-11

Locations

FR (2); NL (9)