Substantially Improving the Cure Rate of High-risk BRCA1-like Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Drug: ddAC-CP-OlaparibDrug: ddAC-mini CTC
- Registration Number
- NCT02810743
- Lead Sponsor
- The Netherlands Cancer Institute
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 174
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ddAC-CP-Olaparib ddAC-CP-Olaparib 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. ddAC-mini CTC ddAC-mini CTC 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.
- Primary Outcome Measures
Name Time Method Overall survival in all patients assessed up to 120 months time from randomization to death from any cause in all patients
- Secondary Outcome Measures
Name Time Method cost-effectiveness measured by costs per quality-adjusted life years (QALYs) assessed up to 120 months cost-effectiveness measured by costs per quality-adjusted life years (QALYs)
Patient reported outcomes assessed up to 24 months Patient reported outcomes; including quality of life (QoL) determined by a comprehensive panel of QoL questionnaires
cost-effectiveness measured by incremental cost-effectiveness ratio (ICER) assessed up to 120 months cost-effectiveness measured by incremental cost-effectiveness ratio (ICER)
Recurrence free interval in all patients assessed up to 120 months time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first in all patients
Recurrence free interval in patients with an HR impaired tumor assessed up to 120 months time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first in patients with an HR impaired tumor
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 Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03
Overall survival in patients without a germline BRCA1/2 mutation assessed up to 120 months time from randomization to death from any cause in without a germline BRCA1/2 mutation
Trial Locations
- Locations (11)
LUMC
🇳🇱Leiden, Netherlands
Medical spectrum Twente
🇳🇱Enschede, Overijssel, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
AZVU
🇳🇱Amsterdam, Netherlands
Hopital Tenon, University Marie-Curie
🇫🇷Paris, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Maastricht University Medical Center
🇳🇱Maastricht, Netherlands
Antoni van Leeuwenhoek
🇳🇱Amsterdam, Netherlands
Radboud UMC
🇳🇱NIjmegen, Netherlands
Erasmus Medical Center Cancer Institute
🇳🇱Rotterdam, Netherlands
University Medical Center Utrecht
🇳🇱Utrecht, Netherlands