Substantially Improving the Cure Rate of High-risk BRCA1-like Breast Cancer Patients With Personalized Therapy (SUBITO) - an International Randomized Phase III Trial
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 174
- 试验地点
- 20
- 主要终点
- Overall survival in all patients
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: ddAC-CP-Olaparib (Drug)
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.
干预措施: ddAC-mini CTC (Drug)
结局指标
主要结局
Overall survival in all patients
时间窗: assessed up to 120 months
time from randomization to death from any cause in all patients
次要结局
- cost-effectiveness measured by costs per quality-adjusted life years (QALYs)(assessed up to 120 months)
- Patient reported outcomes(assessed up to 24 months)
- cost-effectiveness measured by incremental cost-effectiveness ratio (ICER)(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)
- Overall survival in patients without a germline BRCA1/2 mutation(assessed up to 120 months)