Drug and/or Toxin-induced Diarrhea Clinical Trial
Official title:
Randomized, Double-blind, Parallel Group, Placebo-controlled, Dose Finding Study in Colorectal Cancer Patients Receiving 5-FU-based Chemotherapy to Assess the Efficacy of Different Doses of s.c. Elsiglutide in the Prevention of Chemotherapy Induced Diarrhea (CID)
| Verified date | February 2024 |
| Source | Helsinn Healthcare SA |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 498 |
| Est. completion date | February 2016 |
| Est. primary completion date | February 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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. Inclusion criteria will be checked during the screening visit. Inclusion criteria 4 and 6 will be re-checked as applicable on Day 1 of Cycle 1 and Cycle 2. 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. Exclusion criteria 1 to 18 will be checked during the screening visit. Exclusion criteria 19 to 23 should be checked on Day 1 of Cycle 1. Exclusion criteria 7, 8, 9, 11 and 17 to 23 will be re-checked on Day 1 of Cycle 2. |
| Country | Name | City | State |
|---|---|---|---|
| Belarus | Healthcare Institution Brest Regional Oncologic Dispensary | Brest | |
| Belarus | Institution Gomel Regional Clinical Oncology Dispensary | Gomel | |
| Belarus | State Institution "Republic Scientific and Practical Center of oncology and medical radiology n.a.N.N.Alexandrov" | Lesnoy | Minsk Region |
| Belarus | Healthcare Institution Minsk City Clinical Oncologic Dispensary | Minsk | |
| Belarus | Healthcare Institution Mogilev Regional Oncologic Dispensary | Mogilev | |
| Bulgaria | 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 | "Specialized Hospital for Active Treatment of Oncology Diseases - Sofia city" EOOD | Sofia | |
| Bulgaria | "Specialized Hospital for Active Treatment ofOncologal Diseases - Sofia District" | Sofia | |
| Bulgaria | Multifunctional Hospital for Active Treatment for Women's Health Nadezhda Ltd. | Sofia | |
| Czechia | Pardubicka krajska nemocnice a.s | Pardubice | |
| Germany | Klinikum Neuperlach | München | |
| Hungary | Országos Onkológiai Intézet "C" Belgyógyászati-Onkológiai és Klinikai Farmakológiai Osztály | Budapest | |
| Hungary | Semmelweis Egyetem, ÁOK I. Sz. Belgyógyászati Klinika, Onkológiai Részleg | Budapest | |
| Hungary | Uzsoki Utcai Kórház Onkoradiológia, Sugárterápia, ovárosi 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 | |
| Poland | Centrum Medyczne MrukMed | Rzeszów | |
| Poland | Centrum Medyczne Malgorzata | Srem | |
| Poland | Wojewódzki Szpital Zespolony im. Rydygiera | Torun | |
| Russian Federation | State Budgetary Institution of Arkhangelsk Region "Arkhangelsk Clinical Oncology Dispensary" | Arkhangelsk | |
| Russian Federation | Non-State Healthcare Institution "Railway Clinical Hospital at Chelyabinsk Station of Joint Stock Company "Russian Railways" | Chelyabinsk | |
| Russian Federation | State Healthcare Institution "Kursk Regional Clinical Oncology Dispensary" | Kursk | |
| Russian Federation | Federal State Budgetary Institution "Russian Oncology Scientific Centre named after N.N. Blokhin" of the Russian Academy of Medical Science | Moscow | |
| Russian Federation | State Budgetary Healthcare Institution "City Clinical Hospital #40" of the Healthcare Department of Moscow | Moscow | |
| Russian Federation | State Budgetary Healthcare Institution of Moscow "Moscow City Oncology Hospital #62" of Healthcare Department of Moscow | Moscow | |
| Russian Federation | State Budgetary Healthcare Institution of Nizhniy Novgorod Region "Nizhniy Novgorod Regional Oncology Dispensary" | Nizhniy Novgorod | |
| Russian Federation | State Budgetary Healthcare Institution of Nizhny Novgorod region "Clinical Diagnostic centre" | Nizhniy Novgorod | |
| Russian Federation | Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Dispensary" | Omsk | |
| Russian Federation | Budgetary Healthcare Institution of Orel Region "Orel Oncology Dispensary" | Orel | |
| Russian Federation | State Budgetary Healthcare Institution "Orenburg Regional Clinical Oncology Dispensary" | Orenburg | |
| Russian Federation | State Budgetary Healthcare Institution of Perm Territory "Perm Territorial Oncology Dispensary" | Perm | |
| Russian Federation | State Budgetary Healthcare Institution of Stavropol Territory "Pyatigorsk Oncology Dispensary" | Pyatigorsk | |
| Russian Federation | 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 | |
| Russian Federation | State Budgetary Educational Institution of Higher Professional Education "First Saint Petersburg State Medical University named after Academician I.P. Pavlov" | Saint Petersburg | |
| Russian Federation | State Budgetary Healthcare Institution "Saint Petersburg Clinical Theoretical & Practical Centre of Special Types of Medical Care (Oncology)" | Saint Petersburg | |
| Russian Federation | State Healthcare Institution "City Hospital #9" (Saint Petersburg Theoretical & Practical Centre of Coloproctology) | Saint Petersburg | |
| Russian Federation | State Budgetary Healthcare Institution "Samara Regional Clinical Oncology Dispensary" (Chemotherapy Unit #1) | Samara | |
| Russian Federation | State Budgetary Healthcare Institution of Republic of Mordovia "Republican Oncology Dispensary" | Saransk | Republic Of Mordovia |
| Russian Federation | State Budgetary Healthcare Institution "Republican Clinical Oncology Dispensary" | Ufa | |
| Russian Federation | State Budgetary Healthcare Institution "Volgograd Regional Oncology Dispensary" | Volzhskiy | Volgograd Region |
| Ukraine | 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" | Kirovogrado | |
| Ukraine | Regional ?ommunal Institution Kryvyi Rig Oncology Dispensary | Kryvyi Rih | |
| Ukraine | Kyiv City Clinical Oncological Center | Kyiv | |
| Ukraine | Lviv State Oncological Regional Treatment and Preventive Center | Lviv |
| Lead Sponsor | Collaborator |
|---|---|
| Helsinn Healthcare SA | Chiltern International Inc. |
Belarus, Bulgaria, Czechia, Germany, Hungary, Poland, Russian Federation, Ukraine,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Proportion of Patients Experiencing a Maximum Grade = 2 Diarrhea During the First Cycle of Chemotherapy in the Target Population | The endpoint of primary interest for efficacy was the proportion of patients within the Target population experiencing a maximum Grade = 2 diarrhea in Cycle 1 (as assessed by the Investigator). For patient 8031362 who withdrew consent after 11 day in Cycle 1, Investigator assessments for the individual diarrhea events were missing. The data were imputed as Grade 0 for the primary endpoint, in line with the patient's eDiary data. Additional population is not included in primary endpoint evaluation. |
15 days |