Dose Finding Study in Colorectal Cancer Patients Receiving 5-FU-based Chemotherapy to Assess the Efficacy of Elsiglutide in the Prevention of Chemotherapy Induced Diarrhea (CID)

NCT ID: NCT02383810

Last Updated: 2024-03-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 498 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2016-02-29

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.

Conditions

Drug and/or Toxin-induced Diarrhea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Elsiglutide

Intervention Type: 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

Group Type: ACTIVE_COMPARATOR

Elsiglutide

Intervention Type: 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

Group Type: ACTIVE_COMPARATOR

Elsiglutide

Intervention Type: DRUG

Placebo - target population

Placebo once daily as s.c. injection for 4 consecutive days in patients receiving 5-FU based chemotherapy

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Group Type: ACTIVE_COMPARATOR

Elsiglutide

Intervention Type: 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.

Group Type: ACTIVE_COMPARATOR

Elsiglutide

Intervention Type: 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.

Group Type: ACTIVE_COMPARATOR

Elsiglutide

Intervention Type: 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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Elsiglutide

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Written informed consent

2. Male or female > 18 years of age;

3. 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;

4. A performance status of ≤ 2 according to the Eastern Cooperative Oncology Group (ECOG) scale;

5. Non-childbearing female patient or female patient of childbearing potential using reliable contraceptive measures and having negative pregnancy test before treatment administration;

6. Able to read, understand, follow the study procedure and complete patient diary.

Exclusion Criteria

1. Any investigational drugs within 30 days before enrollment or foreseen use of investigational agents during the study;

2. Treatment with chemotherapy of any type within 12 months before enrollment;

3. Patient with any type of ostomy (temporary ostomy should be closed at least 6 months prior to enrollment);

4. Patient who underwent total colectomy;

5. Patient who had abdominal-perineal resection or surgery leaving the patient without a functioning rectum;

6. Any radiotherapy to the abdomen or pelvis in the 6 months prior to enrollment;

7. Scheduled to receive radiotherapy to abdomen or pelvis during the study;

8. a) Exclusion from the Target population Scheduled to receive any concomitant chemotherapeutic agent, other than FOLFOX or FOLFIRI agents; any type of monoclonal antibodies;

8. b) Exclusion from the Additional population Scheduled to receive any concomitant chemotherapeutic agent, other than FOLFOX or FOLFIRI agents;

9. 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;

10. History of chronic (≥ 30 consecutive days) use of laxatives;

11. Active and ongoing systemic infection;

12. Lactating woman;

13. History of hypersensitivity or allergies to drugs or compounds potentially related to this investigational drug class;

14. Previous exposure to Glucagon-like peptide-2 (GLP-2) or other compounds in this investigational drug class;

15. Patient who participated in a previous study with elsiglutide;

16. 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 ;

17. 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;

18. Any medical condition that precludes the administration of chemotherapy;

19. Use of laxatives within 7 days prior to study Day 1;

20. Use of antibiotics within 7 days prior to study Day 1;

21. Any diarrhea in the 48 hours preceding study drug administration on Day 1;

22. Major surgery within the previous 21 days before study Day 1;

23. Use of anti-diarrheal agents and probiotics within the 48 hours prior to study drug administration on study Day 1.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chiltern International Inc.

INDUSTRY

Sponsor Role: collaborator

Helsinn Healthcare SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

State Institution "Republic Scientific and Practical Center of oncology and medical radiology n.a.N.N.Alexandrov"

Lyasny, Minsk Oblast, Belarus

Healthcare Institution Brest Regional Oncologic Dispensary

Brest, , Belarus

Institution Gomel Regional Clinical Oncology Dispensary

Homyel, , Belarus

Healthcare Institution Minsk City Clinical Oncologic Dispensary

Minsk, , Belarus

Healthcare Institution Mogilev Regional Oncologic Dispensary

Mogilev, , Belarus

Specialized Hospital for active treatment in oncology - Haskovo Ltd

Haskovo, , Bulgaria

''Multifunctional Hospital for Active Treatment Central Onco Hospital" Ltd

Plovdiv, , Bulgaria

Complex Oncology Centre - Plovdiv Ltd

Plovdiv, , Bulgaria

Multifunctional Hospital for Active Treatment for Women's Health Nadezhda Ltd.

Sofia, , Bulgaria

"Specialized Hospital for Active Treatment of Oncology Diseases - Sofia city" EOOD

Sofia, , Bulgaria

"Specialized Hospital for Active Treatment ofOncologal Diseases - Sofia District"

Sofia, , Bulgaria

Pardubicka krajska nemocnice a.s

Pardubice, , Czechia

Klinikum Neuperlach

München, , Germany

Semmelweis Egyetem, ÁOK I. Sz. Belgyógyászati Klinika, Onkológiai Részleg

Budapest, , Hungary

Országos Onkológiai Intézet "C" Belgyógyászati-Onkológiai és Klinikai Farmakológiai Osztály

Budapest, , Hungary

Uzsoki Utcai Kórház Onkoradiológia, Sugárterápia, ővárosi Onkoradiológiai Központ

Budapest, , Hungary

Debreceni Egyetem, OEC Onkológiai Tanszék

Debrecen, , Hungary

Somogy Megyei Kaposi Mór Oktató Kórház Klinikai Onkológiai Osztály

Kaposvár, , Hungary

Jósa András Oktatókórház Onkoradiológiai Osztály

Nyíregyháza, , Hungary

Szegedi Tudományegyetem, ÁOK, Szent-Györgyi Albert Klinikai Központ Onkoterápiás Klinika

Szeged, , Hungary

Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház Onkológiai Osztály

Szolnok, , Hungary

Centrum Medyczne Malgorzata

Gmina Śrem, , Poland

Centrum Medyczne MrukMed

Rzeszów, , Poland

Wojewódzki Szpital Zespolony im. Rydygiera

Torun, , Poland

State Budgetary Healthcare Institution of Republic of Mordovia "Republican Oncology Dispensary"

Saransk, Respublika Mordoviya, Russia

State Budgetary Healthcare Institution "Volgograd Regional Oncology Dispensary"

Volzhsky, Volgograd Oblast, Russia

State Budgetary Institution of Arkhangelsk Region "Arkhangelsk Clinical Oncology Dispensary"

Arkhangelsk, , Russia

Non-State Healthcare Institution "Railway Clinical Hospital at Chelyabinsk Station of Joint Stock Company "Russian Railways"

Chelyabinsk, , Russia

State Healthcare Institution "Kursk Regional Clinical Oncology Dispensary"

Kursk, , Russia

Federal State Budgetary Institution "Russian Oncology Scientific Centre named after N.N. Blokhin" of the Russian Academy of Medical Science

Moscow, , Russia

State Budgetary Healthcare Institution "City Clinical Hospital #40" of the Healthcare Department of Moscow

Moscow, , Russia

State Budgetary Healthcare Institution of Moscow "Moscow City Oncology Hospital #62" of Healthcare Department of Moscow

Moscow, , Russia

State Budgetary Healthcare Institution of Nizhny Novgorod region "Clinical Diagnostic centre"

Nizhny Novgorod, , Russia

State Budgetary Healthcare Institution of Nizhniy Novgorod Region "Nizhniy Novgorod Regional Oncology Dispensary"

Nizhny Novgorod, , Russia

Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Dispensary"

Omsk, , Russia

State Budgetary Healthcare Institution "Orenburg Regional Clinical Oncology Dispensary"

Orenburg, , Russia

Budgetary Healthcare Institution of Orel Region "Orel Oncology Dispensary"

Oryol, , Russia

State Budgetary Healthcare Institution of Perm Territory "Perm Territorial Oncology Dispensary"

Perm, , Russia

State Budgetary Healthcare Institution of Stavropol Territory "Pyatigorsk Oncology Dispensary"

Pyatigorsk, , Russia

State Budgetary Educational Institution of Higher Professional Education "First Saint Petersburg State Medical University named after Academician I.P. Pavlov"

Saint Petersburg, , Russia

State Healthcare Institution "City Hospital #9" (Saint Petersburg Theoretical & Practical Centre of Coloproctology)

Saint Petersburg, , Russia

Research Institute of Pulmonology of State Budgetary Educational Institution of Higher Professional Education "First Saint Petersburg State Medical University named after Academician I.P. Pavlov" of the Ministry of Healthcare of the Russian Federation

Saint Petersburg, , Russia

State Budgetary Healthcare Institution "Saint Petersburg Clinical Theoretical & Practical Centre of Special Types of Medical Care (Oncology)"

Saint Petersburg, , Russia

State Budgetary Healthcare Institution "Samara Regional Clinical Oncology Dispensary" (Chemotherapy Unit #1)

Samara, , Russia

State Budgetary Healthcare Institution "Republican Clinical Oncology Dispensary"

Ufa, , Russia

Chernigiv medical and prophylactic establishment "Chernigiv regional oncological center"

Chernihiv, , Ukraine

Communal Institution "Chernivtsi Regional clinical oncology dispensary"

Chernivtsi, , Ukraine

Communal Institution Dnipropetrovsk City Multifunctional Clinical Hospital #4

Dnipropetrovsk, , Ukraine

Ivano-Frankivsk Regional Oncological Center

Ivano-Frankivsk, , Ukraine

Communal Institution Kharkiv Regional Clinical Oncology Center

Kharkiv, , Ukraine

Municipal institution "Kirovograd Regional Oncology Center"

Kropyvnytskyi, , Ukraine

Regional Сommunal Institution Kryvyi Rig Oncology Dispensary

Kryvyi Rih, , Ukraine

Kyiv City Clinical Oncological Center

Kyiv, , Ukraine

Lviv State Oncological Regional Treatment and Preventive Center

Lviv, , Ukraine

Countries

Belarus; Bulgaria; Czechia; Germany; Hungary; Poland; Russia; Ukraine

Other Identifiers

TIDE-13-22

Identifier Type: -

Identifier Source: org_study_id