A Trial of PledOx + FOLFOX6 Compared to Placebo + FOLFOX6 in Patients With Metastatic Colorectal Cancer (PLIANT)
Advanced Metastatic (Stage IV) Colorectal Cancer
About this trial
This is an interventional treatment trial for Advanced Metastatic (Stage IV) Colorectal Cancer focused on measuring Metastatic colorectal cancer, stage IV, FOLFOX6, Chemotherapy, PledOx, Mangafodipir, Febrile neutropenia, Oxidative stress, Antioxidant, neutropenia, neuropathy
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- Moores UCSD Cancer Center
- Center for Cancer and Blood Disorders
- Associates in Oncology & Hematology
- Wellmont Medical Associates Oncology and Hematology
- The University of Texas, Health Science Center at San Antonio
- Benaroya Research Institute @ Virginia Mason
- Complex Oncology Center-Plovdiv EOOD, Department of Medical Oncology and oncology diseases in gastroenterology
- Complex Oncology Center-Shumen EOOD, Department of Medical Oncology
- MHAT "Serdika" EOOD, Department of Medical Oncology
- UMHAT "Tzaritza Joanna-ISUL" EAD, Clinic of Medical Oncology
- SHATO EAD, Sofia, Clinic of Chemotherapy
- Aalborg University Hospital, Dept of Oncology, Clinical Research Unit
- Odense Universitetshospital, Klinisk Forsknings Enhed, Onkologisk Afdelig R
- LTD Clinic Medina
- Resaerch Institte of Clinical Medicine
- JSC "Neo Medi"
- LTD " High Technology Medical Center University Clinic"
- S. Khechinashvili University Hospital
- St. Josef-Hospital -Universitätsklinik Ruhr-Universität Bochum, Leitende Ärztin der Abt. für Hämatologie und Onkologie, Medizinische Klinik I
- BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie -Onkologie
- HELIOS Klinikum Wuppertal, Klinik für Hämatologie und Onkologie
- Centro Hospitalar do Baixo Vouga, E.P.E. (Hospital Infante D. Pedro), Oncologia Médica
- Hospital de Braga, Oncologia Médica
- Instituto Português de Oncologia do Porto, Francisco Gentil, E.P.E., Oncologia Médica
- Institute for Oncology and Radiology of Serbia, Clinic for Medical Oncology
- Military Medical Academy, Gastroenterology department
- Clinical Hospital Center Zemun, Insitute for Oncology
- Clinical Center Kragujevac, Center for Oncology
- Gävle sjukhus, Oncology unit
- Sahlgrenska/Östra sjukhuset
- Universitetssjukhuset i Linköping
- Karolinska Sjukhuset
- Akademiska Sjukhuset
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Active Comparator
Active Comparator
Placebo Comparator
FOLFOX6 + PledOx 2 µmol/kg
FOLFOX6 + PledOx 5 µmol/kg
FOLFOX6 + PledOx 10 µmol/kg
FOLFOX6 + 0,9% NaCl
PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
Placebo= 0.9% NaCl; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.