Immunotherapy in Patients With Early dMMR Rectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 39
- 试验地点
- 5
- 主要终点
- Complete clinical response
研究概览
简要总结
The purpose of this investigator-initiated, multicenter phase II trial is to evaluate the efficacy and tolerability of nivolumab and ipilimumab in patients with stage 1-3 MSI/dMMR rectal cancer.
The primary objective is:
Number of patients with complete clinical response after one or two cycles of immunotherapy.
Patients will be treated with 1 or 2 cycles of combination immunotherapy:
Cycle 1: Nivolumab 3 mg/kg days 1 and 15 & ipilimumab 1 mg/kg day 1 Cycle 2: Nivolumab 3 mg/kg days 50 and 65 & ipilimumab 1 mg/kg day 50
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years.
- •Histologically verified non-metastatic rectal cancer stage 1-
- •No indication for local therapy like TEM.
- •Histologically verified dMMR or MSI.
- •Performance status (WHO) of 0-
- •No previous chemotherapy, radiotherapy or immunotherapy for colorectal cancer
- •Adequate haematological function defined as neutrophils ≥ 1.5 x 109/l and platelets ≥ 100 x 109/l.
- •Adequate organ function (bilirubin ≤ 1.5 x UNL (upper normal limit), GFR (may be calculated) > 30 ml/min.
- •Women of childbearing potential must have been tested negative in a serum pregnancy test within five days prior to registration. Fertile patients must agree to use a highly effective method of birth control. (i.e., pregnancy rate of less than 1 % per year) (Appendix 1) during the study and for six months after the discontinuation of study medication.
- •Has provided written informed consent prior to performance of any study procedure.
- •Written informed consent must be obtained according to the local Ethics Committee requirements.
排除标准
- •Any other condition or therapy, which in the investigator's opinion may pose a risk to the patient or interfere with the study objectives.
- •Concomitant use of systemic glucocorticoids more than the equivalent dose to tablet prednisolone 10 mg/day. Treatment with systemic glucocorticoids must end no later than two weeks before inclusion.
- •Subjects with active, known, or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol.
- •Known allergy or intolerance to any of the drugs used (nivolumab and ipilimumab).
研究组 & 干预措施
nivolumab + ipilimumab
Patients will be treated with 1 or 2 cycles of combination immunotherapy:
Cycle 1: Nivolumab 3 mg/kg days 1 and 15 & ipilimumab 1 mg/kg day 1 Cycle 2: Nivolumab 3 mg/kg days 50 and 65 & ipilimumab 1 mg/kg day 50
干预措施: Nivolumab (Drug)
nivolumab + ipilimumab
Patients will be treated with 1 or 2 cycles of combination immunotherapy:
Cycle 1: Nivolumab 3 mg/kg days 1 and 15 & ipilimumab 1 mg/kg day 1 Cycle 2: Nivolumab 3 mg/kg days 50 and 65 & ipilimumab 1 mg/kg day 50
干预措施: Ipilimumab (Drug)
结局指标
主要结局
Complete clinical response
时间窗: Evaluated at day 93 (+/- 7 days) after one or two cycles of immunotherapy. (Each cycle is 7 weeks)
Proportion of patients with complete clinical response Complete clinical response will be defined as no visible or palpable tumor examined by rectal exploration (if low tumors), endoscopy and MR-scan. Patients with definite but less than complete regression BUT with a representative biopsy without viable tumor cells will also be classified as cCR in this trial.
次要结局
- Complete biological response(Evaluated at day 93 (+/- 7 days) after one or two cycles of immunotherapy. (Each cycle is 7 weeks))
- 12 months recurrence(after 12 months)
- Respons rate(after 1 or 2 cycles of immunotherapy. (Each cycle is 7 weeks))
- Adverse events(after 1 or 2 cycles of immunotherapy and months 4, 10, 16, and 24. (Each cycle is 7 weeks))
- Bio-marker predictive models for treatment response and survival.(after 1 or 2 cycles of immunotherapy. (Each cycle is 7 weeks))
- Quality of life (EORCT QLQ-C30)(after 1 or 2 cycles of immunotherapy and months 4, 10, 16, and 24. (Each cycle is 7 weeks))
- Quality of life (EORCT QLQ-CR29)(after 1 or 2 cycles of immunotherapy and months 4, 10, 16, and 24. (Each cycle is 7 weeks))