A Trial of PledOx + FOLFOX6 Compared to Placebo + FOLFOX6 in Patients With Metastatic Colorectal Cancer (PLIANT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by PledPharma AB
Sponsor:
Collaborator:
Pharma Consulting Group AB
Information provided by (Responsible Party):
PledPharma AB
ClinicalTrials.gov Identifier:
NCT01619423
First received: May 25, 2012
Last updated: September 3, 2014
Last verified: August 2014

May 25, 2012
September 3, 2014
September 2012
May 2015   (final data collection date for primary outcome measure)
Change in Absolute Neutrophil count 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 ] [ Designated as safety issue: No ]
As defined by neutropenia
Same as current
Complete list of historical versions of study NCT01619423 on ClinicalTrials.gov Archive Site
  • Febrile neutropenia [ Time Frame: Every second week, in 16 weeks ] [ Designated as safety issue: No ]
  • CT or MRI of thorax, abdomen and pelvis [ Time Frame: From baseline until progression or up to 16 months, whichever comes first ] [ Designated as safety issue: No ]
    Response Rate (RR) and Progression Free Survival (PFS)as assessed by RECIST 1.1
  • Presence of positive cold allodynia test assessed by subjects [ Time Frame: Every second week, in 16 weeks ] [ Designated as safety issue: No ]
    This assessment is novel and will be measured on 0-10 numerical rating scales where 0 = no pain and 10 = worst possible pain.
  • Oxaliplatin-associated sensory neuropathy [ Time Frame: Every second week, in 16 weeks and thereafter every 12th week for up to 12 months. ] [ Designated as safety issue: No ]
    Assessed by a patient reported outcome scale (Leonard et al.).
  • Physician observed neuropathy [ Time Frame: Every second week, in 16 weeks ] [ Designated as safety issue: No ]
    As defined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and Oxaliplatin Sanofi Specific Scale
  • Oral mucositis [ Time Frame: Every second week, in 16 weeks and thereafter every 12th week for up to 12 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change in FOLFOX6 dose frequency and intensity [ Time Frame: Every second week for up to 16 weeks ] [ Designated as safety issue: No ]
    As compared to standard treatment guidelines
  • Survival [ Time Frame: from baseline up to 24 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Plasma concentration half-life of of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP) [ Time Frame: From time 0 to last observed concentration ] [ Designated as safety issue: No ]
    Dose Escalation phase
  • 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 ] [ Designated as safety issue: No ]
    Dose Escalation phase
  • Area under the plasma concentration versus time curve (AUC) of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP) [ Time Frame: From time 0 to last observed concentration ] [ Designated as safety issue: No ]
    Dose Escalation phase
  • Plasma concentration half-life of of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP) [ Time Frame: From time 0 to last observed concentration ] [ Designated as safety issue: No ]
    Randomization phase
  • 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 ] [ Designated as safety issue: No ]
    Randomization phase
  • Area under the plasma concentration versus time curve (AUC) of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP) [ Time Frame: From time 0 to last observed concentration ] [ Designated as safety issue: No ]
    Randomization phase
  • Electrocardiogram (ECG) [ Time Frame: at appropriate timepoints during the 30 minutes following PledOx administration at the every cycle ] [ Designated as safety issue: Yes ]
    Dose Escalation phase
  • Electrocardiogram (ECG) [ Time Frame: at appropriate timepoints during the 30 minutes following PledOx administration at the first cycle only ] [ Designated as safety issue: Yes ]
    Randomization phase
  • Manganese level in whole blood [ Time Frame: Change from baseline at 16 weeks or end-of-treatment, whatever comes first ] [ Designated as safety issue: No ]
  • Febrile neutropenia [ Time Frame: Every second week, in 16 weeks ] [ Designated as safety issue: No ]
  • CT or MRI of thorax, abdomen and pelvis [ Time Frame: From baseline until progression or up to 16 months, whichever comes first ] [ Designated as safety issue: No ]
    Response Rate (RR) and Progression Free Survival (PFS)as assessed by RECIST 1.1
  • Presence of positive cold and/or touch allodynia test assessed by subjects [ Time Frame: Every second week, in 16 weeks ] [ Designated as safety issue: No ]
    These two assessments are novel and will be measured on 0-10 numerical rating scales where 0 = no pain/no discomfort and 10 = worst possible pain/worst possible discomfort. "Pain" for the cold allodynia test and "discomfort" for the touch allodynia test, respectively.
  • Oxaliplatin-associated sensory neuropathy [ Time Frame: Every second week, in 16 weeks and thereafter every 12th week for up to 12 months. ] [ Designated as safety issue: No ]
    Assessed by a patient reported outcome scale (Leonard et al.).
  • Physician observed neuropathy [ Time Frame: Every second week, in 16 weeks ] [ Designated as safety issue: No ]
    As defined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and Oxaliplatin Sanofi Specific Scale
  • Visual inpection of mouth and throat for oral mucositis [ Time Frame: Every second week, in 16 weeks and thereafter every 12th week for up to 12 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Change in FOLFOX6 dose frequency and intensity [ Time Frame: Every second week for up to 16 weeks ] [ Designated as safety issue: No ]
    As compared to standard treatment guidelines
  • Survival [ Time Frame: from baseline up to 24 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Plasma concentration half-life of of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP) [ Time Frame: before dose, 0 minutes, 15 minutes, 30 minutes, 60 minutes, 4 hours, 8 hours, 12 hours and 24 hours after dosing for the first three cycles of PledOx administration ] [ Designated as safety issue: No ]
    Dose Escalation phase
  • The maximum plasma concentration (Cmax) and the corresponding time (Tmax) of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP) [ Time Frame: before dose, 0 minutes, 15 minutes, 30 minutes, 60 minutes, 4 hours, 8 hours, 12 hours and 24 hours after dosing for the first three cycles of PledOx administration ] [ Designated as safety issue: No ]
    Dose Escalation phase
  • Area under the plasma concentration versus time curve (AUC) of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP) [ Time Frame: before dose, 0 minutes, 15 minutes, 30 minutes, 60 minutes, 4 hours, 8 hours, 12 hours and 24 hours after dosing for the first three cycles of PledOx administration ] [ Designated as safety issue: No ]
    Dose Escalation phase
  • Plasma concentration half-life of of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP) [ Time Frame: before dose, 0 minutes, 15 minutes, 30 minutes, 60 minutes and 4 hours after dosing for the first cycle of PledOx administration ] [ Designated as safety issue: No ]
    Randomization phase
  • The maximum plasma concentration (Cmax) and the corresponding time (Tmax) of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP) [ Time Frame: before dose, 0 minutes, 15 minutes, 30 minutes, 60 minutes and 4 hours after dosing for the first cycle of PledOx administration ] [ Designated as safety issue: No ]
    Randomization phase
  • Area under the plasma concentration versus time curve (AUC) of PledOx (metabolites ZnDPDP, ZnPLED, ZnDPMP) [ Time Frame: before dose, 0 minutes, 15 minutes, 30 minutes, 60 minutes and 4 hours after dosing for the first cycle of PledOx administration ] [ Designated as safety issue: No ]
    Randomization phase
  • Electrocardiogram (ECG) [ Time Frame: at appropriate timepoints during the 30 minutes following PledOx administration at the every cycle ] [ Designated as safety issue: Yes ]
    Dose Escalation phase
  • Electrocardiogram (ECG) [ Time Frame: at appropriate timepoints during the 30 minutes following PledOx administration at the first cycle only ] [ Designated as safety issue: Yes ]
    Randomization phase
  • Manganese level in whole blood [ Time Frame: Change from baseline at 16 weeks or end-of-treatment, whatever comes first ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Trial of PledOx + FOLFOX6 Compared to Placebo + FOLFOX6 in Patients With Metastatic Colorectal Cancer
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

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Advanced Metastatic (Stage IV) Colorectal Cancer
  • Drug: PledOx (2 µmol/kg)
    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.
  • Drug: PledOx (5 µmol/kg)
    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
  • Drug: Placebo (0,9% NaCl)
    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.
  • Active Comparator: FOLFOX6 + PledOx 2 µmol/kg
    Intervention: Drug: PledOx (2 µmol/kg)
  • Active Comparator: FOLFOX6 + PledOx 5 µmol/kg
    Intervention: Drug: PledOx (5 µmol/kg)
  • Placebo Comparator: FOLFOX6 + 0,9% NaCl
    Intervention: Drug: Placebo (0,9% NaCl)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
165
July 2015
May 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
United States,   Sweden
 
NCT01619423
PP095, (PLIANT), 2012-001367-76
Yes
PledPharma AB
PledPharma AB
Pharma Consulting Group AB
Not Provided
PledPharma AB
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP