A Phase II Study of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer
试验速览
- 阶段
- 2 期
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Pelvic complete resection rate
研究概览
简要总结
The concurrent neoadjuvant chemoradiation therapy is standard care for local advanced rectal cancer (LARC), however, this regimen may induce sorts of adverse events, and part of them even more severer. A number of pilot studies had shown high rate of complete resection after neoadjuvant chemotherapy alone, but the results did not increase the ratio of pathological complete response (pCR), which was associated with overall survival (OS). Here, the investigators adopt the three active cytotoxic agents (Fluorouracil, Oxaliplatin, Irinotecan, FOLFOXIRI) as the neoadjuvant chemotherapy regimen to replace the concurrent chemoradiation and to improve the ratio of pCR further.
详细描述
This is a multicenter, phase II trial to assess the efficacy/safety of triplet regimen (FOLFOXIRI) for patients with LARC. After 4 cycles of FOLFOXIRI and 2 weeks later, the patients will be evaluated by senior radiologist, oncologist and surgeon through pelvic MRI, CT and Positron Emission Computed Tomography (PET-CT). The patients will go to surgery (TME) if the tumor response is good enough to have complete resection under the decision of MDT,otherwise, the patients will receive pelvic radiotherapy(45Grey/25Fraction and 5.4Grey/3Fraction boost to the tumor bed) combined with capecitabine(625mg/M^2, bid po, d1-5, qw), and additional four cycles of modified FOLFOX6 (mFOLFOX6) or Oxaliplatin 135mg/m²plus Capecitabine 1.0/m² bid po(XELOX) of each 3 weeks cycle for 2 cycles chemotherapy before TME. All patients will receive 6-8 cycles of mFOLFOX6 or 4-5 cycles XELOX as adjuvant chemotherapy after TME.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 to 75 years at diagnosis
- •Diagnosis of rectal adenocarcinoma
- •ECOG status: 0～1
- •Clinical stage II (T3-4, N0) or stage III (T1-4, N1-2)
- •Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:
- •Leukocytes ≥ 4.0 x109/ L,
- •Absolute neutrophil count (ANC) ≥ 2.0 x109/ L
- •Platelet count ≥ 100 x109/ L,
- •Hemoglobin (Hb) ≥ 9g/ dL.
- •Total bilirubin ≤1.5 x the upper limit of normal (ULN).
- •Alanine aminotransferase (ALT) ≤ 3 x ULN
- •Aspartate aminotransferase (AST) ≤ 3 x ULN.
- •Serum creatinine ≤ 1.5 x the ULN.
- •Signed informed consent;
排除标准
- •Patient had received pelvic radiotherapy
- •Patient had received systemic chemotherapy
- •Pregnant and Nursing women
- •Had metastatic disease
- •Uncontrolled co-morbid illnesses or other concurrent disease
- •Patient had second malignant disease within 5 years
- •Patients refused to signed informed consent.
研究组 & 干预措施
FOLFOXIRI
irinotecan* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle
干预措施: FOLFOXIRI (Drug)
结局指标
主要结局
Pelvic complete resection rate
时间窗: Up to 10 weeks
Pathologic confirmation
次要结局
- The rate of clinical complete response after 4 cycles of FOLFOXIRI(Up to 10 weeks)
- The rate of pathological complete response after 4 cycles of FOLFOXIRI(Up to 10 weeks)
- The incidence of >=3 grade adverse events(2 years)
- The rate of local control(3 years)
- Disease free survival (DFS)(3 years)
- Overall survival(3 years)
- The rate of receive chemoradiation(Up to 10 weeks)