Conditions: Drug and/or Toxin-induced Diarrhea
Keywords: Chemotherapy Induced Diarrhea (CID)
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 498
Healthy volunteers: no

Brief summary:
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.

Detailed description:
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:

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.

Secondary Objectives:

* As a secondary objective, the efficacy of 3 s.c. doses of elsiglutide 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) given in combination with a monoclonal antibody will be explored.
* Safety and tolerability of the administered repeated doses of elsiglutide will be evaluated.

Additionally the following secondary objectives will be explored:

* The pharmacokinetics (PK) of elsiglutide, and its metabolites in each patient who consents to undergo an exposure assessment after the first administration and at steady state. The influence of possible demographic and therapeutic covariates on the PK parameters and their variability will also be investigated. The possible relationship between exposure of elsiglutide and its metabolites and efficacy measures in the target and overall population will be explored.
* The economic impact of the 3 doses of elsiglutide vs. placebo and each other dose in the treatment of CID.
* The impact on patient's QoL (quality of life) of the different dosages vs. placebo.

Arms:
arm 1: Elsiglutide 10 mg once daily as s.c. injection for 4 consecutive days in patients receiving 5-FU based chemotherapy arm 2: Elsiglutide 20 mg once daily as s.c. injection for 4 consecutive days in patients receiving F-FU based chemotherapy arm 3: Elsiglutide 40 mg once daily as s.c. injection for 4 consecutive days in patients receiving 5-FU based chemotherapy arm 4: Placebo once daily as s.c. injection for 4 consecutive days in patients receiving 5-FU based chemotherapy arm 5: Elsiglutide 10 mg once daily as s.c. injection for 4 consecutive days in patients receiving 5-FU based chemotherapy with monoclonal antibody. arm 6: Elsiglutide 20 mg once daily as s.c. injection for 4 consecutive days in patients receiving 5-FU based chemotherapy with monoclonal antibody. arm 7: Elsiglutide 40 mg once daily as s.c. injection for 4 consecutive days in patients receiving 5-FU based chemotherapy with monoclonal antibody. arm 8: Placebo once daily as s.c. injection for 4 consecutive days in patients receiving 5-FU based chemotherapy with monoclonal antibody.

Interventions: intervention 1: Elsiglutide intervention 2: Placebo
Intervention descriptions: intervention 1: None intervention 2: None

Protocol document: