A Phase II Trial of AK104 Combined With Neoadjuvant Chemoradiotherapy in Proficient Mismatch Repair/Microsatellite Stable Locally Advanced Rectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Complete response (CR) rate
研究概览
简要总结
This is an open-label, single-arm study to investigate the efficacy and safety of AK104 (an Anti-PD1 and Anti-CTLA4 Bispecific Antibody) and neoadjuvant chemoradiotherapy in patients with pMMR/MSS locally advanced rectal cancer.
详细描述
The study evaluates the addition of AK104(an Anti-PD1 and Anti-CTLA4 Bispecific Antibody) in neoadjuvant chemoradiotherapy in proficient Mismatch Repair (pMMR) /Microsatellite Stable (MSS) locally advanced rectal cancer (LARC). A total of 33 pMMR/MSS LARC patients will receive long-course chemoradiotherapy plus 2 cycles of AK104, followed by another 3 cycles of AK104, finally received clinical routine manage. The tumor response to treatment, adverse effects and long-term prognosis will be analyzed.
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
- •Rectal adenocarcinoma
- •cT3-4aNany or cT1-4aN+
- •No distant metastasis
- •Location ≤12 cm from the anal verge
- •Positive PD-L1 expression (PD-L1 TPS≥1% or PD-L1 CPS ≥1)
- •the MSI status is MSS and pMMR
- •Sufficient bone marrow, kidney and liver function
- •No previous surgery of the rectum, no previous chemotherapy, no previous pelvic radiation, no previous biotherapy, no immunotherapy
排除标准
- •bowel obstruction
- •Distant metastasis
- •Severe arrhythmia, cardiac dysfunction (NYHA grade III or IV )
- •Uncontrollable severe hypertesion
- •Active severe infection
- •Cachexia, organ dysfunction
- •Previous pelvic radiotherapy or chemotherapy
- •Multiple primary cancers
- •Epileptic seizures
- •Malignant history within 5 years, except cervical carcinoma in situ or cutaneous basal cell carcinoma
- •Persons deprived of liberty or under guardianship
- •Impossibility for compliance to follow-up
- •Certain or suspicious allergy to research drug
- •Pregnant or breast-feeding woman
研究组 & 干预措施
Treatment Arm
A total of 33 pMMR/MSS LARC patients will receive long-course chemoradiotherapy plus 2 cycles of AK104, followed by another 3 cycles of AK104, finally received clinical routine manage.
干预措施: AK104 (Drug)
Treatment Arm
A total of 33 pMMR/MSS LARC patients will receive long-course chemoradiotherapy plus 2 cycles of AK104, followed by another 3 cycles of AK104, finally received clinical routine manage.
干预措施: Capecitabine (Drug)
Treatment Arm
A total of 33 pMMR/MSS LARC patients will receive long-course chemoradiotherapy plus 2 cycles of AK104, followed by another 3 cycles of AK104, finally received clinical routine manage.
干预措施: Neoadjuvant Radiotherapy (Radiation)
结局指标
主要结局
Complete response (CR) rate
时间窗: an average of 6 months.
Rate of complete response (CR), including pathologic complete response (pCR) and clinical complete response (cCR).
次要结局
- Adverse effects(From date of randomization until the date of death from any cause, assessed up to 5 years)
- Overall survival(From date of randomization until the date of death from any cause, assessed up to 60 months.)
- Rate of surgical complications(The surgery was scheduled 2-4 weeks after the end of neoadjuvant therapy. And the surgical complications were assessed up to 1 year from the surgery.)
- Local recurrence free survival(From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.)
- Rate of Major pathologic response and tumor regression grade distribution(an average of 1 year.)
- Disease free survival(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.)
- Long-term anal function(1.5 year after diagnosis)
研究者
WeiWei Xiao
Chief physician
Sun Yat-sen University