A Prospective, Two-cohort Phase II Trial of Standard Systemic Therapy in Combination With High/Low-dose Radiotherapy Plus Toripalimab for Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- PFS
研究概览
简要总结
TORCH-M is a prospective, single-arm, two-cohort, investigator-initiated phase II trial to investigate the efficacy and safety of standard systemic therapy in combination with high/low-dose radiotherapy plus toripalimab in paitents with microsatellite stable metastatic colorectal cancer (MSS mCRC). Eligible patients will be assigned to two cohorts according to previous treatment: a first-line cohort A and a second-line cohort B. Patients in both arms will first receive one cycle of standard systemic therapy and toripalimab, followed by high/low-dose radiotherapy, and then continue with standard systemic therapy and toripalimab.The survival benefits, response rates, and adverse effects will be analyzed.
详细描述
First-line standard systemic therapies in cohort A include: FOLFOX/XELOX+ bevacizumab, FOLFOX/XELOX+cetuximab (KRAS/NRAS/BRAF WT and left-sided tumors only), FOLFIRINOX+ bevacizumab.
Second-line standard systemic therapies in cohort B include: FOLFOX/XELOX+ bevacizumab, FOLFOX/XELOX+cetuximab (KRAS/NRAS/BRAF WT), FOLFIRI/irinotecan+raltitrexed/irinotecan/+bevacizumab, FOLFIRI/irinotecan+raltitrexed/irinotecan/+cetuximab (KRAS/NRAS/BRAF WT), based on the previous first-line chemotherapy and adverse events.
Toripalimab will be delivered at 240 mg q3w. Radiotherapy regimes include 4-8 fractions of 4-12Gy via SABR or hypofractionated radiotherapy (HFRT) and 5 fractions of 0.5-2Gy via LDRT.
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 between18 and 75 years old.
- •An Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Histopathological confirmed MSS/pMMR adenocarcinoma of the colon or rectum.
- •At least one evaluable metastatic lesion for radiotherapy and evaluation according to RECIST 1.
- •Treatment naive (first-line cohort) and progressed on after first-line therapy or stopped first-line therapy due to unacceptable toxic effects (second-line cohort).
- •Prior radiotherapy completed at least 4 weeks before enrollment.
- •Adequate bone-marrow, hepatic, and renal function: neutrophils ≥ 1.5 × 10^9/L, Hb ≥ 90 g/L, PLT ≥ 100 × 10^9/L, ALT/ AST≤2.5 ULN, Cr≤1 ULN.
- •Sign the informed consent and have good compliance.
排除标准
- •Neutrophil < 1.5×10^9/L, PLT < 100×10^9/L (PLT < 80×10^9/L in patients with liver metastasis), or Hb < 90g/L; blood transfusion within 2 weeks before enrollment is not allowed to meet the enrollment criteria.
- •TBIL > 1.5 ULN, or TBIL > 2.5 ULN in patients with liver metastasis. AST or ALT > 2.5 ULN, or ALT and / or AST > 5 ULN in patients with liver metastasis.
- •Cr > 1.5 ULN, or creatinine clearance < 50ml / min (calculated according to Cockcroft Gault formula).
- •APTT > 1.5 ULN, PT > 1.5 ULN (subject to the normal value of the clinical trial research center).
- •Serious electrolyte abnormalities. Urinary protein ≥ 2+, or 24-hour urine protein ≥1.0g/24h. Uncontrolled hypertension: SBP >140mmHg or DBP > 90mmHg. The presence of gastrointestinal diseases such as gastric or duodenal active ulcers, ulcerative colitis or unresected tumours with active bleeding; or other conditions likely to cause gastrointestinal bleeding or perforation; or unhealed gastrointestinal perforation or gastrointestinal fistula after surgical treatment.
- •A history of arterial thrombosis or deep vein thrombosis within 6 months; a history of bleeding or evidence of bleeding tendency within 2 months.
- •A history of heart disease within 6 months (including congestive heart failure, acute myocardial infarction, severe/unstable angina, coronary artery bypass grafting, cardiac insufficiency ≥ NYHA grade 2 and LVEF<50%).
- •Uncontrolled malignant pleural effusion, ascites, or pericardial effusion. History of anti-PD-1, PD-L1, PD-L2, CTLA-4 or any other specific T cell co-stimulation or checkpoint pathway targeted therapy.
- •The presence of a clinically detectable second primary malignancy, or history of other malignancies within 5 years excluding adequately treated non-melanoma skin cancer, carcinoma in situ of cervix and superficial bladder tumour (non-invasive tumour, or carcinoma in situ, or T1).
- •A history of liver disease including, but not limited to HBV infection or HBV DNA positive(≥1×10^4/ml), HCV infection or HCV DNA positive(≥1×10^3/ml) and liver cirrhosis.
- •Pregnant or lactating women or women who may be pregnant have a positive pregnancy test before the first medication; Or the female participants themselves and their partners who were unwilling to implement strict contraception during the study period.
- •The investigator considers that the subject is not suitable to participate in this clinical study due to any clinical or laboratory abnormalities or compliance problems.
- •Serious mental abnormalities. The diameter of brain metastasis is greater than 3cm or the total volume is greater than 30cc.
- •Clinical or radiological evidence of spinal cord compression, or tumours within 3 mm of the spinal cord on MRI.
研究组 & 干预措施
a first-line cohort A and a second-line cohort B
干预措施: standard systemic therapy combined with high/low-dose radiotherapy plus toripalimab (Drug)
结局指标
主要结局
PFS
时间窗: Up to 2 years
Defined as the time from initiation of treatment to PD or death from any cause.
次要结局
- OS(Up to 3 years)
- ORR(Up to 1 year)
- DCR(Up to 1 year)
- Adverse events(Up to 3 years)