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

July 4, 2018 updated by: Egetis Therapeutics

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 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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

186

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Plovdiv, Bulgaria, 4004
        • Complex Oncology Center-Plovdiv EOOD, Department of Medical Oncology and oncology diseases in gastroenterology
      • Shumen, Bulgaria, 9700
        • Complex Oncology Center-Shumen EOOD, Department of Medical Oncology
      • Sofia, Bulgaria, 1303
        • MHAT "Serdika" EOOD, Department of Medical Oncology
      • Sofia, Bulgaria, 1527
        • UMHAT "Tzaritza Joanna-ISUL" EAD, Clinic of Medical Oncology
      • Sofia, Bulgaria, 1756
        • SHATO EAD, Sofia, Clinic of Chemotherapy
  • Denmark
      • Aalborg, Denmark, 9000
        • Aalborg University Hospital, Dept of Oncology, Clinical Research Unit
      • Odense, Denmark, 5000
        • Odense Universitetshospital, Klinisk Forsknings Enhed, Onkologisk Afdelig R
  • Georgia
      • Batumi, Georgia, 6000
        • LTD Clinic Medina
      • Tbilisi, Georgia, 0112
        • Resaerch Institte of Clinical Medicine
      • Tbilisi, Georgia, 0131
        • JSC "Neo Medi"
      • Tbilisi, Georgia, 0144
        • LTD " High Technology Medical Center University Clinic"
      • Tbilisi, Georgia, 179
        • S. Khechinashvili University Hospital
  • Germany
      • Bochum, Germany, 44791
        • St. Josef-Hospital -Universitätsklinik Ruhr-Universität Bochum, Leitende Ärztin der Abt. für Hämatologie und Onkologie, Medizinische Klinik I
      • Dresden, Germany, 01307
        • BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie -Onkologie
      • Wuppertal, Germany, 42283
        • HELIOS Klinikum Wuppertal, Klinik für Hämatologie und Onkologie
  • Portugal
      • Aveiro, Portugal, 3814-501
        • Centro Hospitalar do Baixo Vouga, E.P.E. (Hospital Infante D. Pedro), Oncologia Médica
      • Braga, Portugal, 4710-243
        • Hospital de Braga, Oncologia Médica
      • Porto, Portugal, 4200-072
        • Instituto Português de Oncologia do Porto, Francisco Gentil, E.P.E., Oncologia Médica
  • Serbia
      • Belgrade, Serbia, 11000
        • Institute for Oncology and Radiology of Serbia, Clinic for Medical Oncology
      • Belgrade, Serbia, 11000
        • Military Medical Academy, Gastroenterology department
      • Belgrade, Serbia, 11080
        • Clinical Hospital Center Zemun, Insitute for Oncology
      • Kragujevac, Serbia, 34000
        • Clinical Center Kragujevac, Center for Oncology
  • Sweden
      • Gävle, Sweden, 80187
        • Gävle sjukhus, Oncology unit
      • Göteborg, Sweden, 41685
        • Sahlgrenska/Ostra sjukhuset
      • Linköping, Sweden, SE-581 85
        • Universitetssjukhuset i Linköping
      • Stockholm, Sweden
        • Karolinska Sjukhuset
      • Uppsala, Sweden
        • Akademiska sjukhuset
  • United States
    • California
      • La Jolla, California, United States, 92093-0698
        • Moores UCSD Cancer Center
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • Center For Cancer And Blood Disorders
    • Tennessee
      • Chattanooga, Tennessee, United States, 37421
        • Associates in Oncology & Hematology
      • Kingsport, Tennessee, United States, 37660
        • Wellmont Medical Associates Oncology and Hematology
    • Texas
      • San Antonio, Texas, United States, 78229
        • The University of Texas, Health Science Center at San Antonio
    • Washington
      • Seattle, Washington, United States, 98101
        • Benaroya Research Institute @ Virginia Mason

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: FOLFOX6 + PledOx 2 µmol/kg
PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
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.
Other Names:
  • Calmangafodipir
Active Comparator: FOLFOX6 + PledOx 5 µmol/kg
PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
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
Other Names:
  • Calmangafodipir
Active Comparator: FOLFOX6 + PledOx 10 µmol/kg
PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
Drug: PledOx (10 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
Other Names:
  • Calmangafodipir
Placebo Comparator: FOLFOX6 + 0,9% NaCl
Placebo= 0.9% NaCl; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
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.
Other Names:
  • Sodium chloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With Neuropathy Grade 2 or Higher (According to the Oxaliplatin Specific Sanofi Scale (OSSS) Criteria Related Paraesthesia/Dysaesthesia)
Time Frame: Every second week during cycle 1-8, for up to 16 weeks
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Egetis Therapeutics

Collaborators

Pharma Consulting Group AB

Investigators

  • Study Director: Marie Bengtson, Egetis Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Actual)

March 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

May 25, 2012

First Submitted That Met QC Criteria

June 12, 2012

First Posted (Estimate)

June 14, 2012

Study Record Updates

Last Update Posted (Actual)

July 6, 2018

Last Update Submitted That Met QC Criteria

July 4, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PP095, (PLIANT)
  • 2012-001367-76 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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