Description:
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.
Title
- Brief Title: Substantially Improving the Cure Rate of High-risk BRCA1-like Breast Cancer
- Official Title: Substantially Improving the Cure Rate of High-risk BRCA1-like Breast Cancer Patients With Personalized Therapy (SUBITO) - an International Randomized Phase III Trial
Clinical Trial IDs
- ORG STUDY ID:
M16BRC
- NCT ID:
NCT02810743
Conditions
Interventions
Drug | Synonyms | Arms |
---|
ddAC-CP-Olaparib | | ddAC-CP-Olaparib |
ddAC-mini CTC | | ddAC-mini CTC |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
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. | |
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. | |
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Maximum Eligible Age: | 65 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Overall survival |
Time Frame: | assessed up to 120 months |
Safety Issue: | |
Description: | time from randomization to death from any cause. |
Secondary Outcome Measures
Measure: | Recurrence free interval |
Time Frame: | assessed up to 120 months |
Safety Issue: | |
Description: | time from randomization to local recurrence, second primary, distant recurrence or death, whichever comes first |
Measure: | Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03 |
Time Frame: | up to 30 days after end of treatment |
Safety Issue: | |
Description: | Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03 |
Measure: | cost-effectiveness measured by costs per quality-adjusted life years (QALYs) |
Time Frame: | assessed up to 120 months |
Safety Issue: | |
Description: | cost-effectiveness measured by costs per quality-adjusted life years (QALYs) |
Measure: | Patient reported outcomes |
Time Frame: | assessed up to 24 months |
Safety Issue: | |
Description: | Patient reported outcomes; including quality of life (QoL) determined by a comprehensive panel of QoL questionnaires |
Measure: | cost-effectiveness measured by incremental cost-effectiveness ratio (ICER) |
Time Frame: | assessed up to 120 months |
Safety Issue: | |
Description: | cost-effectiveness measured by incremental cost-effectiveness ratio (ICER) |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | The Netherlands Cancer Institute |
Trial Keywords
- Stage III
- HER2 negative
- homologous recombination deficiency (HRD)
Last Updated
June 15, 2021