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

Diarrhea Clinical Trial

Official title:

Phase II, Double-blind, Randomized, Two-stage, Placebo-controlled Proof of Concept Study in Colorectal Cancer Patients Receiving 5-FU Based Chemotherapy to Assess the Efficacy of Elsiglutide (ZP1846)Administered s.c. in the Prevention of Chemotherapy Induced Diarrhea(CID)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01543451
• Other study ID #: TIDE-11-10
• Status: Completed
• Phase: Phase 2
• First received: February 21, 2012
• Last updated: February 27, 2014
• Start date: February 2012
• Est. completion date: October 2013

Study information

• Verified date: February 2014
• Source: Helsinn Healthcare SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBulgaria: Ministry of HealthHungary: National Institute of PharmacyRomania: National Medicines AgencyRussia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: October 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diarrhea

Intervention

Drug:
• Elsiglutide
24 mg administered s.c. once daily for 4 consecutive days from Day 1 chemotherapy
• Placebo
24 mg administered s.c. once daily for 4 consecutive days from Day 1 chemotherapy

Locations

Country	Name	City	State
Bulgaria	Department of Chemotherapy, Complex Oncology Center	Ruse
Bulgaria	Chemotherapy Department, Complex Oncology Center	Shumen
Bulgaria	Department of Chemotherapy Specialized Hospital for Active Treatment of Oncological Diseases	Sofia
Bulgaria	Department of Chemotherapy Specialized Hospital for Active Treatment of Oncological Diseases	Sofia
Bulgaria	Oncology Clinic, Multiprofile Hospital for Active Treatment "Sveta Marina"	Varna
Hungary	Semmelweis University, Department of Diagnostic Radiology and Oncotherapy	Budapest
Hungary	Kenezy Hospital, Department of Clinical Pharmacology, Infectology and Allergology	Debrecen
Hungary	Petz Aladar County Teaching Hospital, Center of Oncologic Radiology Hungary	Gyor
Hungary	Szeged Medical University Department of Oncology and Oncotherapy	Szeged
Romania	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	Prof. Dr. Ion Chiricuta Institute of Oncology, Medical Oncology Department	Cluj-Napoca	Cluj County
Romania	Euroclinic Oncology Center SRL - Medical Oncology Department	Iasi	Iasi county
Romania	Sf. Ioan cel Nou Emergency Clincal County Hospital	Suceava	Suceava county
Russian Federation	Regional Oncology Center	Arkhangelsk
Russian Federation	Kursk Regional Clinical Oncology Center	Kursk
Russian Federation	Pyatigorsk Oncology Center	Pyatigorsk
Russian Federation	City #9 Hospital	Saint-Petersburg	St. Petersburg
Russian Federation	City Clinical Oncology Center	Saint-Petersburg	St. Petersburg
Russian Federation	Regional Clinical Oncology Center - Chemotherapy Department	Ulyanovsk	Ulyanovsk region
Russian Federation	Regional Oncology Hospital	Yaroslavl

Sponsors (1)

Lead Sponsor	Collaborator
Helsinn Healthcare SA

Countries where clinical trial is conducted

Bulgaria,  Hungary,  Romania,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients experiencing Diarrhea	Severity of Diarrhea will be classified according to the NCI-CTCAE.	Day 1 to Day 14	No
Secondary	Safety and tolerability of the administered repeated doses of elsiglutide (ZP1846) will be evaluated	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	Day 1 to Day 32	Yes
Secondary	PK of elsiglutide will be evaluated	The followin standard PK parameters will be evaluated: Tmax, Cmax, AUC0-t, AUC0-24, AUC0-8, t1/2Z, ?Z, 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	Day 1 to Day 5	No