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
  Purpose

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.


Condition Intervention Phase
Advanced Metastatic (Stage IV) Colorectal Cancer
Drug: PledOx (2 µmol/kg)
Drug: PledOx (5 µmol/kg)
Drug: Placebo (0,9% NaCl)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by PledPharma AB:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 165
Study Start Date: September 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: FOLFOX6 + PledOx 2 µmol/kg 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.
Active Comparator: FOLFOX6 + PledOx 5 µmol/kg 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
Placebo Comparator: FOLFOX6 + 0,9% NaCl 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01619423

Locations
United States, Florida
Research- Hen/Onc Associates of the Treasure Coast Recruiting
Port St. Lucie, Florida, United States, 34952
Contact: Mary Cheli    772-924-2274      
Principal Investigator: Nicholas Iannotti, M.D         
United States, Tennessee
Associates in Oncology & Hematology Recruiting
Chattanooga, Tennessee, United States, 37421
Contact: Kim Donelson, LPN    423-622-2337      
Principal Investigator: Jitendra Gandhi, M.D.         
United States, Texas
The University of Texas, Health Science Center at San Antonio Recruiting
San Antonio, Texas, United States, 78229
Contact: Jennifer Moseley       MoseleyJ@uthscsa.edu   
Principal Investigator: Devalingam Mahalingam, MD, PhD         
Sweden
Universitetssjukhuset i Linköping Active, not recruiting
Linköping, Sweden, SE-581 85
Karolinska Sjukhuset Recruiting
Stockholm, Sweden
Contact: Mia Karlberg, MD       mia.karlberg@karolinska.se   
Principal Investigator: Mia Karlberg, MD         
Akademiska Sjukhuset Recruiting
Uppsala, Sweden
Contact: Bengt Glimelius, MD, PhD       bengt.glimelius@akademiska.se   
Principal Investigator: Bengt Glimelius, MD, PhD         
Sponsors and Collaborators
PledPharma AB
Pharma Consulting Group AB
  More Information

No publications provided

Responsible Party: PledPharma AB
ClinicalTrials.gov Identifier: NCT01619423     History of Changes
Other Study ID Numbers: PP095, (PLIANT), 2012-001367-76
Study First Received: May 25, 2012
Last Updated: September 3, 2014
Health Authority: United States: Food and Drug Administration
Denmark: Danish Medicines Agency
Sweden: Medical Products Agency
Germany: Federal Institute for Drugs and Medical Devices
Bulgaria: Bulgarian Drug Agency
Georgia: Ministry of Health
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Portugal: National Pharmacy and Medicines Institute

Keywords provided by PledPharma AB:
Metastatic colorectal cancer
stage IV
FOLFOX6
Chemotherapy
PledOx
Mangafodipir
Febrile neutropenia
Oxidative stress
Antioxidant
neutropenia

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on September 18, 2014