Proof-of-Concept Study in Cancer Patients to Assess Efficacy of Elsiglutide in Preventing Chemotherapy-Induced Diarrhea

Phase 2

Completed

• Conditions: Diarrhea
• Interventions: Drug: Placebo; Drug: Elsiglutide

• Registration Number: NCT01543451
• Lead Sponsor: Helsinn Healthcare SA

Brief Summary

The main objective of this study will be to obtain data on the efficacy of elsiglutide in preventing Chemotherapy Induced Diarrhea (CID) in patients with colorectal cancer receiving 5-FU based chemotherapy (FOLFOX4 or FOLFIRI regimen) in comparison to placebo.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-02
• Study First Submitted: 2012-02-21
• Study First Submitted QC: 2012-02-27
• Study First Posted: 2012-03-05
• Primary Completion: 2013-01
• Study Completion: 2013-10
• Status Verified: 2014-02
• Disposition First Submitted: 2014-02-27
• Disposition First Submitted QC: 2014-02-27
• Last Update Submitted: 2014-02-27
• Disposition First Posted: 2014-03-26
• Last Update Posted: 2014-03-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 138

Inclusion Criteria

1. Written informed consent;

2. Male or female patient ≥ 18 years of age;

3. Confirmed diagnosis of colorectal cancer;

4. Chemotherapy naïve patient;

5. Patient scheduled to receive a FOLFOX4 or FOLFIRI chemotherapy regimen according to the following scheme and dosage (1st cycle):

   AGENT DOSE ROUTE/DURATION DAYS Oxaliplatin or Irinotecan 85/180 mg m2 i.v. infusion/2h 1 FolinicAcid (leucovorin) 200 mg m2 i.v. infusion/2h 1+2 5-Fluorouracil (5FU) 400 mg m2 i.v. bolus 1+2 5-Fluorouracil (5FU) 600 mg m2 i.v. infusion/22h 1+2

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

7. Non-fertile patient or fertile patient (male or female) using reliable contraceptive measures

8. Female patient of childbearing potential; need to have a negative pregnancy test at screening.

Inclusion criteria 1-8 will be verified at screening.

Inclusion criteria 8 will be re-confirmed on Day 1.

Exclusion Criteria

1. Inability to understand study procedures and/or cooperate with the study Investigator;

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

3. Patient with any type of ostomy;

4. Any previous radiotherapy to the abdomen or pelvis;

5. Scheduled to receive radiotherapy to abdomen or pelvis during the study (Day 1 to Day 14);

6. Scheduled to receive any concomitant chemotherapeutic agent other than FOLFOX4 or FOLFIRI agents (Oxaliplatin, Irinotecan, Folinic acid, 5-FU) from Day 1 to Day 14;

7. Previous use or scheduled to receive monoclonal antibodies (e.g. bevacizumab, cetuximab, etc) during the study (From Day 1 to Day 14);

8. Major surgery within the previous 3 weeks;

9. Any type of condition leading to chronic diarrhea, including but not limited to inflammatory bowel diseases (e.g. ulcerative colitis and Crohn's disease), chronic diarrhea of presumed or confirmed infectious origin and irritable bowel syndrome;

10. Any diarrhea in the 48 hours preceding study drug administration;

11. Use of anti-diarrheal agents within the 48 hours prior to study drug administration;

12. Use of laxatives within 7 days prior to study drug administration;

13. Use of antibiotics within 7 days prior to study drug administration;

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

15. Active and ongoing systemic infection;

16. Lactating woman;

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

18. Previous exposure to GLP-2 or other compounds in this investigational drug class;

19. Abnormal laboratory values, including

    • Aspartate aminotransferase (AST) ≥ 5 x upper limit of normal
    • Alanine aminotransferase (ALT) ≥ 5 x upper limit of normal
    • Bilirubin > 2 mg/dL (34 μmol/L)
    • Creatinine > 2 mg/dL (177 μmol/L)
    • Albumine < 2 g/dL (20 g/L)
    • Neutrophils< 1.5 x109/L
    • Platelet count < 100 x109/L;

20. Concomitant bleeding disorders;

21. Other serious concomitant illness, which could interfere with the study;

22. Patient who participated in a previous study with elsiglutide (ZP1846).

Exclusion criteria 1-9 and 12-22 will be verified at screening. Exclusion criteria 10 and 11 will be checked on Day 1 only. Exclusion criteria 12, 13 and 15 will be re-checked on Day 1.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Elsiglutide	Elsiglutide	-

Primary Outcome Measures

Name	Time	Method
Number of Patients experiencing Diarrhea	Day 1 to Day 14	Severity of Diarrhea will be classified according to the NCI-CTCAE.

Secondary Outcome Measures

Name	Time	Method
PK of elsiglutide will be evaluated	Day 1 to Day 5	The followin standard PK parameters will be evaluated: Tmax, Cmax, AUC0-t, AUC0-24, AUC0-∞, t1/2Z, λZ, CL/F, VZ/F, the effect of multiple dosing will be evaluated (accumulation ratio). Blood sampling for PK will be performed at: pre-dose, 2h, 4, 6, 12, 24 h post-dose
Safety and tolerability of the administered repeated doses of elsiglutide (ZP1846) will be evaluated	Day 1 to Day 32	Safety will be evaluated by monitoring: * Physical examination; * Vital signs; * Clinical laboratory parameters (hematology, blood chemistry, urinalysis); * 12-lead ECG; * AEs; * Immunogenicity testing in a subset of patients

Trial Locations

Locations (20)

Department of Chemotherapy, Complex Oncology Center; 🇧🇬 Ruse, Bulgaria

Chemotherapy Department, Complex Oncology Center; 🇧🇬 Shumen, Bulgaria

Petz Aladar County Teaching Hospital, Center of Oncologic Radiology Hungary; 🇭🇺 Gyor, Hungary

Sf. Ioan cel Nou Emergency Clincal County Hospital; 🇷🇴 Suceava, Suceava county, Romania

Euroclinic Oncology Center SRL - Medical Oncology Department; 🇷🇴 Iasi, Iasi county, Romania

Regional Clinical Oncology Center - Chemotherapy Department; 🇷🇺 Ulyanovsk, Ulyanovsk region, Russian Federation

Pyatigorsk Oncology Center; 🇷🇺 Pyatigorsk, Russian Federation

Kursk Regional Clinical Oncology Center; 🇷🇺 Kursk, Russian Federation

Oncology Clinic, Multiprofile Hospital for Active Treatment "Sveta Marina"; 🇧🇬 Varna, Bulgaria

Kenezy Hospital, Department of Clinical Pharmacology, Infectology and Allergology; 🇭🇺 Debrecen, Hungary

Semmelweis University, Department of Diagnostic Radiology and Oncotherapy; 🇭🇺 Budapest, Hungary

Prof. Dr. Ion Chiricuta Institute of Oncology, Medical Oncology Department; 🇷🇴 Cluj-Napoca, Cluj County, Romania

City #9 Hospital; 🇷🇺 Saint-Petersburg, St. Petersburg, Russian Federation

Regional Oncology Hospital; 🇷🇺 Yaroslavl, Russian Federation

City Clinical Oncology Center; 🇷🇺 Saint-Petersburg, St. Petersburg, Russian Federation

Department of Chemotherapy Specialized Hospital for Active Treatment of Oncological Diseases; 🇧🇬 Sofia, Bulgaria

Szeged Medical University Department of Oncology and Oncotherapy; 🇭🇺 Szeged, Hungary

Dr. Constantin Opris Clinical Country Emergency Hospital Baia Mare, Department of Oncology; 🇷🇴 Baia Mare, Maramures County, Romania

Fundeni Clinical Institute - Medical Oncology Department; 🇷🇴 Bucharest, Romania

Regional Oncology Center; 🇷🇺 Arkhangelsk, Russian Federation