A Phase Ib Study to Evaluate the Efficacy and Safety of AL2846 Capsule Combined With Chemotherapy (mFOLFOX6 or FOLFIRI)Versus Placebo Combined With Chemotherapy in Subjects With Advanced Colorectal Cancer
试验速览
- 阶段
- 1 期
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
This is a study to explore the safety, tolerance and efficacy of AL2846 capsules combined with mFOLFOLX6 or FOLFIRI standard chemotherapy regimen in subjects with advanced metastatic colorectal cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Histologically confirmed advanced metastatic colorectal cancer.
- •Has received only first-line standard chemotherapy regimen for metastatic disease, and which was failed.
- •At least one measurable lesion.
- •Has received systemic chemotherapy, palliative radiotherapy or other anti-tumor therapy before first dose at least 4 weeks.
- •5.18 and 75 years old; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy ≥ 3 months.
- •Adequate laboratory indicators.
- •No pregnant or breastfeeding women, and a negative pregnancy test.
- •Understood and signed an informed consent form.
排除标准
- •Diagnosed and/or treated additional malignancy within 5 years with the exception of basal cell carcinoma of the skin and carcinoma in situ of the cervix.
- •Has received radiotherapy, chemotherapy and surgery before and less than 4 weeks from the first administration and less than 5 half-lives of oral targeted drugs after the completion of treatment.
- •Has multiple factors that affect oral medications.
- •Has gastroduodenal ulcer, ulcerative colitis, intestinal obstruction and other gastrointestinal diseases or other conditions judged by the investigator that may cause gastrointestinal bleeding or perforation.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
- •Has arterial or deep vein thrombosis events in 6 months.
- •Hypersensitivity to AL2846 or its excipient.
- •Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with blood vessels is unclear.
- •Has symptomatic brain metastases, spinal cord compression, and cancerous meningitis within 8 weeks,or brain or pia mater disease confirmed by CT or MRI examination before the first dose.
- •10.Has adverse events caused by previous therapy that did not recover to ≤ grade 1, with the exception of alopecia or ≥ grade 2 neurotoxicity caused by Oxaliplatin.
- •Subjects plan to receive FOLFIRI chemotherapy regimen with uridine diphosphate glucuronyltransferase homozygous variant or double hybrid variant.
- •Has drug abuse history that unable to abstain from or mental disorders.
- •Has any serious and/or uncontrolled disease.
- •Has received allogeneic organ transplants, hematopoietic stem cell transplants or bone marrow transplants.
- •Has participated in other clinical trials within 4 weeks before the first dose.
- •According to the investigators' judgment.
研究组 & 干预措施
AL2846 + mFOLFOX6
AL2846 capsule administered orally,once daily in 28-day cycle; oxaliplatin 85mg/ ㎡ administered intravenously (IV) on day 1, day 15 in 28-day cycle；calcium folate 400mg/ ㎡ IV on day 1, day 15 in 28-day cycle；5-fu 2800mg/ ㎡ IV on day 1, 2, 15, 16 in 28-day cycle.
干预措施: AL2846 (Drug)
AL2846 + mFOLFOX6
AL2846 capsule administered orally,once daily in 28-day cycle; oxaliplatin 85mg/ ㎡ administered intravenously (IV) on day 1, day 15 in 28-day cycle；calcium folate 400mg/ ㎡ IV on day 1, day 15 in 28-day cycle；5-fu 2800mg/ ㎡ IV on day 1, 2, 15, 16 in 28-day cycle.
干预措施: Calcium folate (Drug)
AL2846 + mFOLFOX6
AL2846 capsule administered orally,once daily in 28-day cycle; oxaliplatin 85mg/ ㎡ administered intravenously (IV) on day 1, day 15 in 28-day cycle；calcium folate 400mg/ ㎡ IV on day 1, day 15 in 28-day cycle；5-fu 2800mg/ ㎡ IV on day 1, 2, 15, 16 in 28-day cycle.
干预措施: 5-FU (Drug)
AL2846 + mFOLFOX6
AL2846 capsule administered orally,once daily in 28-day cycle; oxaliplatin 85mg/ ㎡ administered intravenously (IV) on day 1, day 15 in 28-day cycle；calcium folate 400mg/ ㎡ IV on day 1, day 15 in 28-day cycle；5-fu 2800mg/ ㎡ IV on day 1, 2, 15, 16 in 28-day cycle.
干预措施: Oxaliplatin (Drug)
AL2846 + FOLFIRI
AL2846 capsule administered orally,once daily in 28-day cycle; irinotecan 180mg/㎡ administered intravenously (IV) on day 1,15 in 28-day cycle; calcium folate 400mg/ ㎡ IV on day 1,15 in 28-day cycle; 5-fu 2800mg/ ㎡ IV on day 1, 2, 15, 16 days in 28-day cycle.
干预措施: AL2846 (Drug)
AL2846 + FOLFIRI
AL2846 capsule administered orally,once daily in 28-day cycle; irinotecan 180mg/㎡ administered intravenously (IV) on day 1,15 in 28-day cycle; calcium folate 400mg/ ㎡ IV on day 1,15 in 28-day cycle; 5-fu 2800mg/ ㎡ IV on day 1, 2, 15, 16 days in 28-day cycle.
干预措施: Calcium folate (Drug)
AL2846 + FOLFIRI
AL2846 capsule administered orally,once daily in 28-day cycle; irinotecan 180mg/㎡ administered intravenously (IV) on day 1,15 in 28-day cycle; calcium folate 400mg/ ㎡ IV on day 1,15 in 28-day cycle; 5-fu 2800mg/ ㎡ IV on day 1, 2, 15, 16 days in 28-day cycle.
干预措施: 5-FU (Drug)
AL2846 + FOLFIRI
AL2846 capsule administered orally,once daily in 28-day cycle; irinotecan 180mg/㎡ administered intravenously (IV) on day 1,15 in 28-day cycle; calcium folate 400mg/ ㎡ IV on day 1,15 in 28-day cycle; 5-fu 2800mg/ ㎡ IV on day 1, 2, 15, 16 days in 28-day cycle.
干预措施: Irinotecan (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: up to 12 month
PFS defined as the time from the first dose until the first documented progressive disease (PD) or death from any cause, based on investigator.
次要结局
- Overall response rate (ORR)(up to 12 month)
- Disease control rate（DCR）(up to 12 month)
- Duration of response (DOR)(up to 12 month)