Clinical trial NCT01543451: Proof-of-Concept Study in Cancer Patients to Assess Efficacy of Elsiglutide in Preventing Chemotherapy-Induced Diarrhea
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diarrhea
Lead sponsor: Helsinn Healthcare SA
Sponsor class: INDUSTRY
First posted: 2012-03-05
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Patients experiencing Diarrhea
timeFrame: Day 1 to Day 14
Secondary outcomes:
measure: Safety and tolerability of the administered repeated doses of elsiglutide (ZP1846) will be evaluated
timeFrame: Day 1 to Day 32
measure: PK of elsiglutide will be evaluated
timeFrame: Day 1 to Day 5
Other outcomes:
Locations:
city: Ruse
country: Bulgaria
facility: Department of Chemotherapy, Complex Oncology Center
city: Shumen
country: Bulgaria
facility: Chemotherapy Department, Complex Oncology Center
city: Sofia
country: Bulgaria
facility: Department of Chemotherapy Specialized Hospital for Active Treatment of Oncological Diseases
city: Sofia
country: Bulgaria
facility: Department of Chemotherapy Specialized Hospital for Active Treatment of Oncological Diseases
city: Varna
country: Bulgaria
facility: Oncology Clinic, Multiprofile Hospital for Active Treatment "Sveta Marina"
city: Budapest
country: Hungary
facility: Semmelweis University, Department of Diagnostic Radiology and Oncotherapy
city: Debrecen
country: Hungary
facility: Kenezy Hospital, Department of Clinical Pharmacology, Infectology and Allergology
city: Gyor
country: Hungary
facility: Petz Aladar County Teaching Hospital, Center of Oncologic Radiology Hungary
city: Szeged
country: Hungary
facility: Szeged Medical University Department of Oncology and Oncotherapy
city: Cluj-Napoca
country: Romania
facility: Prof. Dr. Ion Chiricuta Institute of Oncology, Medical Oncology Department
state: Cluj County
city: Iasi
country: Romania
facility: Euroclinic Oncology Center SRL - Medical Oncology Department
state: Iasi county
city: Baia Mare
country: Romania
facility: Dr. Constantin Opris Clinical Country Emergency Hospital Baia Mare, Department of Oncology
state: Maramures County
city: Suceava
country: Romania
facility: Sf. Ioan cel Nou Emergency Clincal County Hospital
state: Suceava county
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute - Medical Oncology Department
city: Saint-Petersburg
country: Russian Federation
facility: City #9 Hospital
state: St. Petersburg
city: Saint-Petersburg
country: Russian Federation
facility: City Clinical Oncology Center
state: St. Petersburg
city: Ulyanovsk
country: Russian Federation
facility: Regional Clinical Oncology Center - Chemotherapy Department
state: Ulyanovsk region
city: Arkhangelsk
country: Russian Federation
facility: Regional Oncology Center
city: Kursk
country: Russian Federation
facility: Kursk Regional Clinical Oncology Center
city: Pyatigorsk
country: Russian Federation
facility: Pyatigorsk Oncology Center
city: Yaroslavl
country: Russian Federation
facility: Regional Oncology Hospital
Study officials:
References: