A Trial of PledOx + FOLFOX6 Compared to Placebo + FOLFOX6 in Patients With Metastatic Colorectal Cancer
- Conditions
- Advanced Metastatic (Stage IV) Colorectal Cancer
- Interventions
- Registration Number
- NCT01619423
- Lead Sponsor
- Egetis Therapeutics
- Brief Summary
The present trial is designed to determine whether pre-treatment with PledOx lowers the frequency and severity of side effects from FOLFOX6 administration in patients with metastatic colorectal cancer.
The efficacy of PledOx will be assessed when added to FOLFOX6 chemotherapy as first line treatment of metastatic colorectal cancer.
This study was performed in multiple parts/phases. Part 1 was an open dose-escalation study with the doses 2, 5 and 10 micromol/kg of calmangafodipir. No study outcomes were planned for this part. In part 2a, participants randomly received either Placebo, 2 or 10 micromol/kg of calmangafodipir. In part 2b, participants randomly received either Placebo, 2 or 5 micromol/kg of calmangafodipir. The overall intent of the study was to compare the effect of antioxidant agent PledOx against placebo in one of three different doses/combinations (2 micromol/kg, 5/10 micromol/kg, 2/5/10 micromol/kg vs. placebo, in the first 8 cycles of FOLFOX6 treatment
- Detailed Description
Globally, nearly 800 000 colorectal cancers are believed to occur annually. Approximately about half of the patients with colorectal cancer develop metastatic disease. These patients are often offered chemotherapy with the FOLFOX6 regimen (FOL = FOLic acid; F = Fluorouracil (5-FU); OX = OXaliplatin) The use of FOLFOX6 is, however, hampered by a high incidence and severity of adverse reactions.
In the current trial patients will receive the antioxidant agent PledOx in one of two different doses, or placebo, in the first 8 cycles of FOLFOX6 treatment.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 186
- Advanced metastatic colorectal (stage IV) cancer verified by biopsy
- Patients may have received up to three previous treatment lines of chemotherapy, which may include fluoropyrimidine, irinotecan and targeted therapies. The last dose of antitumor drug must be given at least 4 weeks prior to inclusion and all toxicity (except alopecia and fatigue) resolved. Patients may also be chemotherapy-naïve, have received prior adjuvant treatment but no previous treatment with oxaliplatin
- CT-scan or MRI of thorax, abdomen and pelvis; within ≤4 weeks before start of chemotherapy
- Evaluable disease and one measurable site of disease according to RECIST 1.1 criteria (at least 10mm for CT-scan or MRI)
- Neurological examination with no significant pathological findings
- ≥18 years
- WHO performance status 0≤2 and Life expectancy ≥ 3 months
- Adequate haematological function, Hb ≥ 100 g/L, ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L
- Adequate renal and hepatic functions: creatinine clearance >50 cc/min, total bilirubin ≤ 1.5 times ULN, ASAT and ALAT ≤ 3 times ULN (ASAT and ALAT ≤ 5 times ULN in case of liver metastases)
- INR ≤1.5 times ULN, unless receiving therapeutic anticoagulation
- Negative pregnancy test for females of child-producing potential
- Written informed consent given
- Tumours other than colorectal adenocarcinomas (within the previous 5 years) except for curatively treated non melanoma skin cancer or in situ carcinoma of the cervix
- Evidence of central nervous system metastases
- Unresolved bowel obstruction or sub-obstruction, uncontrolled Crohn's disease or ulcerative colitis
- History of cardiac disease with a New York Heart Association (NYHA) Class II or greater congestive heart failure, myocardial infarction or unstable angina in the past six (6) months prior to Day 1 of treatment and serious arrhythmias requiring medication for treatment
- Prolonged QTC interval >450 msec
- Known history of stroke or cerebrovascular accident in the past six (6) months
- Severe diarrhoea
- Chronic infection or uncontrolled serious illness causing immunodeficiency
- Any uncontrolled serious illness or medical condition
- Received mangafodipir at any time
- Welders, mine workers or other workers in occupations (current or past) where high manganese exposure is likely
- Pre-existing neurodegenerative disease (Parkinson's, Alzheimer's, Huntington's etc.) or neuromuscular disorder (Multiple sclerosis, Amyotrophic lateral sclerosis, Polio, hereditary neuromuscular disease)
- Major psychiatric disorder (major depression, psychosis)
- Participation in another clinical study with an investigational medicinal product within 1 month prior to inclusion.
- Blood manganese concentration values >18.3 μg/L at screening
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FOLFOX6 + PledOx 2 µmol/kg PledOx (2 µmol/kg) PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin. FOLFOX6 + PledOx 5 µmol/kg PledOx (5 µmol/kg) PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin. FOLFOX6 + PledOx 10 µmol/kg PledOx (10 µmol/kg) PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin. FOLFOX6 + 0,9% NaCl Placebo (0,9% NaCl) Placebo= 0.9% NaCl; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
- Primary Outcome Measures
Name Time Method Number of Patients With Neuropathy Grade 2 or Higher (According to the Oxaliplatin Specific Sanofi Scale (OSSS) Criteria Related Paraesthesia/Dysaesthesia) Every second week during cycle 1-8, for up to 16 weeks Percentage of patients, over cycle 1 to 8, with neuropathy grade 2 or higher (according to the Oxaliplatin Specific Sanofi Scale (OSSS) criteria related paraesthesiae/dysaesthesiae)
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (33)
UMHAT "Tzaritza Joanna-ISUL" EAD, Clinic of Medical Oncology
🇧🇬Sofia, Bulgaria
LTD " High Technology Medical Center University Clinic"
🇬🇪Tbilisi, Georgia
Karolinska Sjukhuset
🇸🇪Stockholm, Sweden
BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie -Onkologie
🇩🇪Dresden, Germany
HELIOS Klinikum Wuppertal, Klinik für Hämatologie und Onkologie
🇩🇪Wuppertal, Germany
Wellmont Medical Associates Oncology and Hematology
🇺🇸Kingsport, Tennessee, United States
The University of Texas, Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Benaroya Research Institute @ Virginia Mason
🇺🇸Seattle, Washington, United States
Sahlgrenska/Östra sjukhuset
🇸🇪Göteborg, Sweden
Hospital de Braga, Oncologia Médica
🇵🇹Braga, Portugal
Institute for Oncology and Radiology of Serbia, Clinic for Medical Oncology
🇷🇸Belgrade, Serbia
Clinical Center Kragujevac, Center for Oncology
🇷🇸Kragujevac, Serbia
Resaerch Institte of Clinical Medicine
🇬🇪Tbilisi, Georgia
JSC "Neo Medi"
🇬🇪Tbilisi, Georgia
Military Medical Academy, Gastroenterology department
🇷🇸Belgrade, Serbia
LTD Clinic Medina
🇬🇪Batumi, Georgia
S. Khechinashvili University Hospital
🇬🇪Tbilisi, Georgia
Moores UCSD Cancer Center
🇺🇸La Jolla, California, United States
Center for Cancer and Blood Disorders
🇺🇸Bethesda, Maryland, United States
Associates in Oncology & Hematology
🇺🇸Chattanooga, Tennessee, United States
Complex Oncology Center-Plovdiv EOOD, Department of Medical Oncology and oncology diseases in gastroenterology
🇧🇬Plovdiv, Bulgaria
MHAT "Serdika" EOOD, Department of Medical Oncology
🇧🇬Sofia, Bulgaria
Complex Oncology Center-Shumen EOOD, Department of Medical Oncology
🇧🇬Shumen, Bulgaria
Aalborg University Hospital, Dept of Oncology, Clinical Research Unit
🇩🇰Aalborg, Denmark
SHATO EAD, Sofia, Clinic of Chemotherapy
🇧🇬Sofia, Bulgaria
Odense Universitetshospital, Klinisk Forsknings Enhed, Onkologisk Afdelig R
🇩🇰Odense, Denmark
Centro Hospitalar do Baixo Vouga, E.P.E. (Hospital Infante D. Pedro), Oncologia Médica
🇵🇹Aveiro, Portugal
St. Josef-Hospital -Universitätsklinik Ruhr-Universität Bochum, Leitende Ärztin der Abt. für Hämatologie und Onkologie, Medizinische Klinik I
🇩🇪Bochum, Germany
Instituto Português de Oncologia do Porto, Francisco Gentil, E.P.E., Oncologia Médica
🇵🇹Porto, Portugal
Gävle sjukhus, Oncology unit
🇸🇪Gävle, Sweden
Clinical Hospital Center Zemun, Insitute for Oncology
🇷🇸Belgrade, Serbia
Universitetssjukhuset i Linköping
🇸🇪Linköping, Sweden
Akademiska Sjukhuset
🇸🇪Uppsala, Sweden