Randomized, Double-blind, Parallel Group, Placebo-controlled, Dose Finding Study in Colorectal Cancer Patients Receiving 5-FU-based Chemotherapy to Assess the Efficacy of Different Doses of s.c. Elsiglutide in the Prevention of Chemotherapy Induced Diarrhea (CID)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 498
- 试验地点
- 54
- 主要终点
- Proportion of Patients Experiencing a Maximum Grade ≥ 2 Diarrhea During the First Cycle of Chemotherapy in the Target Population
研究概览
简要总结
This is a randomized, stratified, double-blind, double-dummy, parallel group, placebo-controlled, dose finding, multicentre, multinational, phase II study in patient with colorectal cancer receiving 5- Fluorouracil (5-FU)-based chemotherapy (FOLFOX or FOLFIRI). Patients will receive, starting from the day of chemotherapy administration, a single daily dose subcutaneously (s.c.) of elsiglutide 10, 20 or 40 mg or placebo for 4 consecutive days. Each patient will be in the study for 3 consecutive chemotherapy cycles. The treatment period for each patient will be 4 consecutive days at each of the first 2 chemotherapy cycles.
The primary objective is to compare the efficacy of 3 s.c. doses of elsiglutide versus (vs.) placebo and vs. each other dose in the prevention of CID in colorectal cancer patients treated with 5-FU based chemotherapy (FOLFOX or FOLFIRI) with no addition of a monoclonal antibody.
详细描述
This is a randomized, stratified, double-blind, double-dummy, parallel group, placebo-controlled, dose finding, multicentre, multinational, phase II study in patient with colorectal cancer receiving 5- Fluorouracil (5-FU)-based chemotherapy (FOLFOX -FOLinic acid, Fluorouracil, OXaliplatin chemotherapy regimen - or FOLFIRI - FOLinic acid, Fluorouracil, IRInotecan chemotherapy regimen). Patients will receive, starting from the day of chemotherapy administration, a single daily dose subcutaneously (s.c.) of elsiglutide 10, 20 or 40 mg or placebo for 4 consecutive days. Each patient will be in the study for 3 consecutive chemotherapy cycles. The treatment period for each patient will be 4 consecutive days at each of the first 2 chemotherapy cycles.
Randomization will be performed with a 1:1:1:1 treatment allocation and will be stratified by chemotherapy regimen and country. Two populations are planned for this study.
The population receiving FOLFOX or FOLFIRI without monoclonal antibody is defined as the Target population, while the population concomitantly receiving monoclonal antibody is defined as the Additional population.
Randomization in Target and Additional population are handled independently.
Primary Objective:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Written informed consent
- •Male or female > 18 years of age;
- •Histologically or cytologically confirmed diagnosis of colorectal cancer
- •Inclusion in the Target Population: Scheduled to receive at least 3 consecutive cycles of the same regimen of FOLFOX or FOLFIRI without monoclonal antibody;
- •Inclusion in the Additional Population: Scheduled to receive at least 3 consecutive cycles of the same regimen of FOLFOX or FOLFIRI in combination with monoclonal antibody;
- •A performance status of ≤ 2 according to the Eastern Cooperative Oncology Group (ECOG) scale;
- •Non-childbearing female patient or female patient of childbearing potential using reliable contraceptive measures and having negative pregnancy test before treatment administration;
- •Able to read, understand, follow the study procedure and complete patient diary.
- •Inclusion criteria will be checked during the screening visit. Inclusion criteria 4 and 6 will be re-checked as applicable on Day 1 of Cycle 1 and Cycle 2.
排除标准
- •Any investigational drugs within 30 days before enrollment or foreseen use of investigational agents during the study;
- •Treatment with chemotherapy of any type within 12 months before enrollment;
- •Patient with any type of ostomy (temporary ostomy should be closed at least 6 months prior to enrollment);
- •Patient who underwent total colectomy;
- •Patient who had abdominal-perineal resection or surgery leaving the patient without a functioning rectum;
- •Any radiotherapy to the abdomen or pelvis in the 6 months prior to enrollment;
- •Scheduled to receive radiotherapy to abdomen or pelvis during the study;
- •a) Exclusion from the Target population Scheduled to receive any concomitant chemotherapeutic agent, other than FOLFOX or FOLFIRI agents; any type of monoclonal antibodies;
- •b) Exclusion from the Additional population Scheduled to receive any concomitant chemotherapeutic agent, other than FOLFOX or FOLFIRI agents;
- •Any type of condition leading to diarrhea, including but not limited to inflammatory bowel diseases (e.g. ulcerative colitis and Crohn's disease), diarrhea of presumed or confirmed infectious origin and irritable bowel syndrome, celiac disease, lactose intolerance, pancreas, liver or diverticular disease, alcohol abuse;
- •History of chronic (≥ 30 consecutive days) use of laxatives;
- •Active and ongoing systemic infection;
- •Lactating woman;
- •History of hypersensitivity or allergies to drugs or compounds potentially related to this investigational drug class;
- •Previous exposure to Glucagon-like peptide-2 (GLP-2) or other compounds in this investigational drug class;
- •Patient who participated in a previous study with elsiglutide;
- •Patient with abnormalities in selected laboratory parameters, including:
- •Aspartate aminotransferase (AST) ≥ 5 x upper limit of normal
- •Alanine aminotransferase (ALT) ≥ 5 x upper limit of normal
- •Bilirubin > 1.5 x upper limit of normal
- •Creatinine > 2 mg/dL (177 μmol/L)
- •Albumine < 2 g/dL (20 g/L)
- •Neutrophils < 1.5 x109/L
- •Platelet count < 100 x109/L ;
- •Any illness or condition that, in the opinion of the investigator, may confound the results of the study or pose unwarranted risk in administering the investigational product to the patient;
- •Any medical condition that precludes the administration of chemotherapy;
- •Use of laxatives within 7 days prior to study Day 1;
- •Use of antibiotics within 7 days prior to study Day 1;
- •Any diarrhea in the 48 hours preceding study drug administration on Day 1;
- •Major surgery within the previous 21 days before study Day 1;
- •Use of anti-diarrheal agents and probiotics within the 48 hours prior to study drug administration on study Day
- •Exclusion criteria 1 to 18 will be checked during the screening visit. Exclusion criteria 19 to 23 should be checked on Day 1 of Cycle
- •Exclusion criteria 7, 8, 9, 11 and 17 to 23 will be re-checked on Day 1 of Cycle 2.
研究组 & 干预措施
Elsiglutide 10 mg - target population
Elsiglutide 10 mg once daily as s.c. injection for 4 consecutive days in patients receiving 5-FU based chemotherapy
干预措施: Elsiglutide (Drug)
Elsiglutide 20 mg - target population
Elsiglutide 20 mg once daily as s.c. injection for 4 consecutive days in patients receiving F-FU based chemotherapy
干预措施: Elsiglutide (Drug)
Elsiglutide 40 mg - target population
Elsiglutide 40 mg once daily as s.c. injection for 4 consecutive days in patients receiving 5-FU based chemotherapy
干预措施: Elsiglutide (Drug)
Placebo - target population
Placebo once daily as s.c. injection for 4 consecutive days in patients receiving 5-FU based chemotherapy
干预措施: Placebo (Drug)
Elsiglutide 10 mg - additional population
Elsiglutide 10 mg once daily as s.c. injection for 4 consecutive days in patients receiving 5-FU based chemotherapy with monoclonal antibody.
干预措施: Elsiglutide (Drug)
Elsiglutide 20 mg - additional population
Elsiglutide 20 mg once daily as s.c. injection for 4 consecutive days in patients receiving 5-FU based chemotherapy with monoclonal antibody.
干预措施: Elsiglutide (Drug)
Elsiglutide 40 mg - additional population
Elsiglutide 40 mg once daily as s.c. injection for 4 consecutive days in patients receiving 5-FU based chemotherapy with monoclonal antibody.
干预措施: Elsiglutide (Drug)
Placebo - additional population
Placebo once daily as s.c. injection for 4 consecutive days in patients receiving 5-FU based chemotherapy with monoclonal antibody.
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of Patients Experiencing a Maximum Grade ≥ 2 Diarrhea During the First Cycle of Chemotherapy in the Target Population
时间窗: 15 days
The endpoint of primary interest for efficacy was the proportion of patients within the Target population experiencing a maximum Grade ≥ 2 diarrhea in Cycle 1 (as assessed by the Investigator). For patient 8031362 who withdrew consent after 11 day in Cycle 1, Investigator assessments for the individual diarrhea events were missing. The data were imputed as Grade 0 for the primary endpoint, in line with the patient's eDiary data. Additional population is not included in primary endpoint evaluation.
次要结局
未报告次要终点