Advanced Metastatic (Stage IV) Colorectal Cancer Clinical Trial
— PLIANTOfficial title:
A Double Blinded Randomised Three Armed Phase II Trial of PledOx in Two Different Doses in Combination With FOLFOX6 Compared to Placebo + FOLFOX6 in Patients With Advanced Metastatic Colorectal (Stage IV) Cancer
| Verified date | July 2018 |
| Source | PledPharma AB |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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
| Status | Completed |
| Enrollment | 186 |
| Est. completion date | December 2016 |
| Est. primary completion date | March 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| Bulgaria | Complex Oncology Center-Plovdiv EOOD, Department of Medical Oncology and oncology diseases in gastroenterology | Plovdiv | |
| Bulgaria | Complex Oncology Center-Shumen EOOD, Department of Medical Oncology | Shumen | |
| Bulgaria | MHAT "Serdika" EOOD, Department of Medical Oncology | Sofia | |
| Bulgaria | SHATO EAD, Sofia, Clinic of Chemotherapy | Sofia | |
| Bulgaria | UMHAT "Tzaritza Joanna-ISUL" EAD, Clinic of Medical Oncology | Sofia | |
| Denmark | Aalborg University Hospital, Dept of Oncology, Clinical Research Unit | Aalborg | |
| Denmark | Odense Universitetshospital, Klinisk Forsknings Enhed, Onkologisk Afdelig R | Odense | |
| Georgia | LTD Clinic Medina | Batumi | |
| Georgia | JSC "Neo Medi" | Tbilisi | |
| Georgia | LTD " High Technology Medical Center University Clinic" | Tbilisi | |
| Georgia | Resaerch Institte of Clinical Medicine | Tbilisi | |
| Georgia | S. Khechinashvili University Hospital | Tbilisi | |
| Germany | St. Josef-Hospital -Universitätsklinik Ruhr-Universität Bochum, Leitende Ärztin der Abt. für Hämatologie und Onkologie, Medizinische Klinik I | Bochum | |
| Germany | BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie -Onkologie | Dresden | |
| Germany | HELIOS Klinikum Wuppertal, Klinik für Hämatologie und Onkologie | Wuppertal | |
| Portugal | Centro Hospitalar do Baixo Vouga, E.P.E. (Hospital Infante D. Pedro), Oncologia Médica | Aveiro | |
| Portugal | Hospital de Braga, Oncologia Médica | Braga | |
| Portugal | Instituto Português de Oncologia do Porto, Francisco Gentil, E.P.E., Oncologia Médica | Porto | |
| Serbia | Clinical Hospital Center Zemun, Insitute for Oncology | Belgrade | |
| Serbia | Institute for Oncology and Radiology of Serbia, Clinic for Medical Oncology | Belgrade | |
| Serbia | Military Medical Academy, Gastroenterology department | Belgrade | |
| Serbia | Clinical Center Kragujevac, Center for Oncology | Kragujevac | |
| Sweden | Gävle sjukhus, Oncology unit | Gävle | |
| Sweden | Sahlgrenska/Östra sjukhuset | Göteborg | |
| Sweden | Universitetssjukhuset i Linköping | Linköping | |
| Sweden | Karolinska Sjukhuset | Stockholm | |
| Sweden | Akademiska Sjukhuset | Uppsala | |
| United States | Center for Cancer and Blood Disorders | Bethesda | Maryland |
| United States | Associates in Oncology & Hematology | Chattanooga | Tennessee |
| United States | Wellmont Medical Associates Oncology and Hematology | Kingsport | Tennessee |
| United States | Moores UCSD Cancer Center | La Jolla | California |
| United States | The University of Texas, Health Science Center at San Antonio | San Antonio | Texas |
| United States | Benaroya Research Institute @ Virginia Mason | Seattle | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| PledPharma AB | Pharma Consulting Group AB |
United States, Bulgaria, Denmark, Georgia, Germany, Portugal, Serbia, Sweden,
Glimelius B, Manojlovic N, Pfeiffer P, Mosidze B, Kurteva G, Karlberg M, Mahalingam D, Buhl Jensen P, Kowalski J, Bengtson M, Nittve M, Näsström J. Persistent prevention of oxaliplatin-induced peripheral neuropathy using calmangafodipir (PledOx(®)): a pla — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Patients With Neuropathy Grade 2 or Higher (According to the Oxaliplatin Specific Sanofi Scale (OSSS) Criteria Related Paraesthesia/Dysaesthesia) | 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) | Every second week during cycle 1-8, for up to 16 weeks |