Overview

This trial is active, not recruiting.

Condition advanced metastatic (stage iv) colorectal cancer
Treatments pledox (2 µmol/kg), pledox (5 µmol/kg), placebo (0,9% nacl)
Phase phase 1/phase 2
Sponsor PledPharma AB
Collaborator Pharma Consulting Group AB
Start date September 2012
End date March 2016
Trial size 165 participants
Trial identifier NCT01619423, 2012-001367-76, PP095, (PLIANT)

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 two different doses of PledOx will be assessed when added to FOLFOX6 chemotherapy as first line treatment of metastatic colorectal cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Arm
(Active Comparator)
PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
pledox (2 µmol/kg) Calmangafodipir
PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.
(Active Comparator)
PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
pledox (5 µmol/kg) Calmangafodipir
PledOx is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles
(Placebo Comparator)
Placebo= 0.9% NaCl; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
placebo (0,9% nacl) Sodium chloride
Placebo (0,9% NaCl) is administered intravenously for up to 5 minutes, about 10 min prior to start of FOLFOX6 chemotherapy which will be administered day 1 and 2 every second week for up to 8 cycles.

Primary Outcomes

Measure
Presence of neuropathy grade 2 or higher (according to the Sanofi-NCI criteria for oxaliplatin related paraesthesiae/dysaesthesiae)
time frame: Every second week, in 16 weeks and thereafter every 12th week for up to 12 months

Secondary Outcomes

Measure
Febrile neutropenia
time frame: Every second week, in 16 weeks
CT or MRI of thorax, abdomen and pelvis
time frame: From baseline until progression or up to 16 months, whichever comes first
Presence of positive cold allodynia test assessed by subjects
time frame: Every second week, in 16 weeks
Oxaliplatin-associated sensory neuropathy
time frame: Every second week, in 16 weeks and thereafter every 12th week for up to 12 months.
Change in Absolute Neutrophil count from both baseline and in between readings
time frame: Every second week, in 16 weeks
Oral mucositis
time frame: Every second week, in 16 weeks and thereafter every 12th week for up to 12 months
Change in white blood cell count both from baseline and in between readings
time frame: Every second week, in 16 weeks and thereafter every 12th week up to 12 months
Change in platelet count from both baseline and in between readings
time frame: Every second week, in 16 weeks adn thereafter every 12th week for up to 12 months
Change in haemoglobin from both baseline and in between readings
time frame: Every second week, in 16 weeks and thereafter every 12th week for up to 12 months
Change in FOLFOX6 dose frequency and intensity
time frame: Every second week for up to 16 weeks
Survival
time frame: from baseline up to 24 months
Change in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) from baseline
time frame: Every second week, in 16 weeks and thereafter every 12th week for up to 12 months
Plasma concentration half-life of of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP)
time frame: From time 0 to last observed concentration
The maximum plasma concentration (Cmax) and the corresponding time (Tmax) of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP)
time frame: From time 0 to last observed concentration
Area under the plasma concentration versus time curve (AUC) of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP)
time frame: From time 0 to last observed concentration
Plasma concentration half-life of of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP)
time frame: From time 0 to last observed concentration
The maximum plasma concentration (Cmax) and the corresponding time (Tmax) of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP)
time frame: From time 0 to last observed concentration
Area under the plasma concentration versus time curve (AUC) of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP)
time frame: From time 0 to last observed concentration
Electrocardiogram (ECG)
time frame: at appropriate timepoints during the 30 minutes following PledOx administration at the every cycle
Electrocardiogram (ECG)
time frame: at appropriate timepoints during the 30 minutes following PledOx administration at the first cycle only
Manganese level in whole blood
time frame: Change from baseline at 16 weeks or end-of-treatment, whatever comes first

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official 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
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.
Trial information was received from ClinicalTrials.gov and was last updated in April 2015.
Information provided to ClinicalTrials.gov by PledPharma AB.