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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Helsinn Healthcare SA
ClinicalTrials.gov Identifier:
NCT01543451
First received: February 21, 2012
Last updated: February 27, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Diarrhea
Drug: Elsiglutide
Drug: Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Helsinn Healthcare SA:

Primary Outcome Measures:
  • Number of Patients experiencing Diarrhea [ Time Frame: Day 1 to Day 14 ] [ Designated as safety issue: No ]
    Severity of Diarrhea will be classified according to the NCI-CTCAE.


Secondary Outcome Measures:
  • Safety and tolerability of the administered repeated doses of elsiglutide (ZP1846) will be evaluated [ Time Frame: Day 1 to Day 32 ] [ Designated as safety issue: Yes ]

    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

  • PK of elsiglutide will be evaluated [ Time Frame: Day 1 to Day 5 ] [ Designated as safety issue: No ]

    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



Enrollment: 138
Study Start Date: February 2012
Study Completion Date: October 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Elsiglutide Drug: Elsiglutide
24 mg administered s.c. once daily for 4 consecutive days from Day 1 chemotherapy
Placebo Comparator: Placebo Drug: Placebo
24 mg administered s.c. once daily for 4 consecutive days from Day 1 chemotherapy

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01543451

Locations
Bulgaria
Department of Chemotherapy, Complex Oncology Center
Ruse, Bulgaria, 7002
Chemotherapy Department, Complex Oncology Center
Shumen, Bulgaria, 9700
Department of Chemotherapy Specialized Hospital for Active Treatment of Oncological Diseases
Sofia, Bulgaria, 1784
Department of Chemotherapy Specialized Hospital for Active Treatment of Oncological Diseases
Sofia, Bulgaria, 1233
Oncology Clinic, Multiprofile Hospital for Active Treatment "Sveta Marina"
Varna, Bulgaria, 9010
Hungary
Semmelweis University, Department of Diagnostic Radiology and Oncotherapy
Budapest, Hungary, H-1082
Kenezy Hospital, Department of Clinical Pharmacology, Infectology and Allergology
Debrecen, Hungary, H-4043
Petz Aladar County Teaching Hospital, Center of Oncologic Radiology Hungary
Gyor, Hungary, 9024
Szeged Medical University Department of Oncology and Oncotherapy
Szeged, Hungary, H-6720
Romania
Prof. Dr. Ion Chiricuta Institute of Oncology, Medical Oncology Department
Cluj-Napoca, Cluj County, Romania, 400015
Euroclinic Oncology Center SRL - Medical Oncology Department
Iasi, Iasi county, Romania, 700106
Dr. Constantin Opris Clinical Country Emergency Hospital Baia Mare, Department of Oncology
Baia Mare, Maramures County, Romania, 430031
Sf. Ioan cel Nou Emergency Clincal County Hospital
Suceava, Suceava county, Romania, 720237
Fundeni Clinical Institute - Medical Oncology Department
Bucharest, Romania, 022328
Russian Federation
City #9 Hospital
Saint-Petersburg, St. Petersburg, Russian Federation, 197110
City Clinical Oncology Center
Saint-Petersburg, St. Petersburg, Russian Federation, 198255
Regional Clinical Oncology Center - Chemotherapy Department
Ulyanovsk, Ulyanovsk region, Russian Federation, 432063
Regional Oncology Center
Arkhangelsk, Russian Federation, 163045
Kursk Regional Clinical Oncology Center
Kursk, Russian Federation, 305035
Pyatigorsk Oncology Center
Pyatigorsk, Russian Federation, 357502
Regional Oncology Hospital
Yaroslavl, Russian Federation, 150054
Sponsors and Collaborators
Helsinn Healthcare SA
  More Information

No publications provided

Responsible Party: Helsinn Healthcare SA
ClinicalTrials.gov Identifier: NCT01543451     History of Changes
Other Study ID Numbers: TIDE-11-10
Study First Received: February 21, 2012
Last Updated: February 27, 2014
Health Authority: United States: Food and Drug Administration
Bulgaria: Ministry of Health
Hungary: National Institute of Pharmacy
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation

Additional relevant MeSH terms:
Diarrhea
Signs and Symptoms, Digestive
Signs and Symptoms

ClinicalTrials.gov processed this record on July 29, 2014