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Advanced Metastatic (Stage IV) Colorectal CancerPhase 1/2PLIANTNCT01619423

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

A Phase 1/2 study testing PledOx (2 µmol/kg), PledOx (5 µmol/kg) and PledOx (10 µmol/kg) in people with Advanced Metastatic (Stage IV) Colorectal Cancer, run by Egetis Therapeutics AB (publ) at 33 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
PledOx (2 µmol/kg), PledOx (5 µmol/kg) and PledOx (10 µmol/kg)
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
186 participants
Where
33 sitesin 8 countries
Study dates
Sep 2012to Dec 2016
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 12Show fewer
  • 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

Who cannot join

  • 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
Show all 15Show fewer
  • 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

Trial locations and contacts

33 sites in 8 countries.

33 sites in 8 countries

United States6 sites

  • Center for Cancer and Blood Disorders

    Bethesda, Maryland, 20817

  • Associates in Oncology & Hematology

    Chattanooga, Tennessee, 37421

  • Wellmont Medical Associates Oncology and Hematology

    Kingsport, Tennessee, 37660

  • Moores UCSD Cancer Center

    La Jolla, California, 92093-0698

  • The University of Texas, Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • Benaroya Research Institute @ Virginia Mason

    Seattle, Washington, 98101

Other trials in United States

Bulgaria5 sites

  • Complex Oncology Center-Plovdiv EOOD, Department of Medical Oncology and oncology diseases in gastroenterology

    Plovdiv, 4004

  • Complex Oncology Center-Shumen EOOD, Department of Medical Oncology

    Shumen, 9700

  • MHAT "Serdika" EOOD, Department of Medical Oncology

    Sofia, 1303

  • UMHAT "Tzaritza Joanna-ISUL" EAD, Clinic of Medical Oncology

    Sofia, 1527

  • SHATO EAD, Sofia, Clinic of Chemotherapy

    Sofia, 1756

Other trials in Bulgaria

Georgia5 sites

  • LTD Clinic Medina

    Batumi, 6000

  • Resaerch Institte of Clinical Medicine

    Tbilisi, 0112

  • JSC "Neo Medi"

    Tbilisi, 0131

  • LTD " High Technology Medical Center University Clinic"

    Tbilisi, 0144

  • S. Khechinashvili University Hospital

    Tbilisi, 179

Other trials in Georgia

Sweden5 sites

  • Gävle sjukhus, Oncology unit

    Gävle, 80187

  • Sahlgrenska/Östra sjukhuset

    Gothenburg, 41685

  • Universitetssjukhuset i Linköping

    Linköping, SE-581 85

  • Karolinska Sjukhuset

    Stockholm

  • Akademiska Sjukhuset

    Uppsala

Other trials in Sweden

Serbia4 sites

  • Institute for Oncology and Radiology of Serbia, Clinic for Medical Oncology

    Belgrade, 11000

  • Military Medical Academy, Gastroenterology department

    Belgrade, 11000

  • Clinical Hospital Center Zemun, Insitute for Oncology

    Belgrade, 11080

  • Clinical Center Kragujevac, Center for Oncology

    Kragujevac, 34000

Other trials in Serbia

Germany3 sites

  • St. Josef-Hospital -Universitätsklinik Ruhr-Universität Bochum, Leitende Ärztin der Abt. für Hämatologie und Onkologie, Medizinische Klinik I

    Bochum, 44791

  • BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie -Onkologie

    Dresden, 01307

  • HELIOS Klinikum Wuppertal, Klinik für Hämatologie und Onkologie

    Wuppertal, 42283

Other trials in Germany

Portugal3 sites

  • Centro Hospitalar do Baixo Vouga, E.P.E. (Hospital Infante D. Pedro), Oncologia Médica

    Aveiro, 3814-501

  • Hospital de Braga, Oncologia Médica

    Braga, 4710-243

  • Instituto Português de Oncologia do Porto, Francisco Gentil, E.P.E., Oncologia Médica

    Porto, 4200-072

Other trials in Portugal

Denmark2 sites

  • Aalborg University Hospital, Dept of Oncology, Clinical Research Unit

    Aalborg, 9000

  • Odense Universitetshospital, Klinisk Forsknings Enhed, Onkologisk Afdelig R

    Odense, 5000

Other trials in Denmark

About this study

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

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

Read the 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.

Being tested
PledOx (2 µmol/kg), PledOx (5 µmol/kg), PledOx (10 µmol/kg), Placebo (0,9% NaCl)
Keywords
Metastatic colorectal cancer, stage IV, FOLFOX6, Chemotherapy, PledOx, Mangafodipir, Febrile neutropenia, Oxidative stress, Antioxidant, neutropenia, neuropathy
Medical subject headings
Colorectal Neoplasms, Febrile Neutropenia, Neutropenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PledOx (2 µmol/kg)Drug

    Also called 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.

  • PledOx (5 µmol/kg)Drug

    Also called 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

  • PledOx (10 µmol/kg)Drug

    Also called 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 (0,9% NaCl)Drug

    Also called 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.

Study groups in NCT01619423
Study groupRoleWhat they receive
FOLFOX6 + PledOx 2 µmol/kgActive comparatorPledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
Receives: Drug: PledOx (2 µmol/kg)
FOLFOX6 + PledOx 5 µmol/kgActive comparatorPledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
Receives: Drug: PledOx (5 µmol/kg)
FOLFOX6 + PledOx 10 µmol/kgActive comparatorPledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
Receives: Drug: PledOx (10 µmol/kg)
FOLFOX6 + 0,9% NaClPlacebo comparatorPlacebo= 0.9% NaCl; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.
Receives: Drug: Placebo (0,9% NaCl)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: Every second week during cycle 1-8, for up to 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jun 2012 (estimated)
  2. Study startSep 2012
  3. Primary completionMar 2016
  4. Study completionDec 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
The study is a three arm study, however, we changed the high dose in the secord part of the study, from 10 micromol/kg (part 2a) to 5 mictomol/kg (part 2b)
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
186 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01619423
Sponsor's protocol ID
PP095, (PLIANT)
Other IDs
2012-001367-76
Acronym
PLIANT
Status last verified
Jul 2018
First submitted
25 May 2012
Last updated
6 Jul 2018
Data monitoring committee
Yes

Publications

  • Glimelius B, Manojlovic N, Pfeiffer P, Mosidze B, Kurteva G, Karlberg M, Mahalingam D, Buhl Jensen P, Kowalski J, Bengtson M, Nittve M, Nasstrom J. Persistent prevention of oxaliplatin-induced peripheral neuropathy using calmangafodipir (PledOx(R)): a placebo-controlled randomised phase II study (PLIANT). Acta Oncol. 2018 Mar;57(3):393-402. doi: 10.1080/0284186X.2017.1398836. Epub 2017 Nov 15.

    PubMed 29140155

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing PledOx (2 µmol/kg), PledOx (5 µmol/kg) and PledOx (10 µmol/kg) in people with Advanced Metastatic (Stage IV) Colorectal Cancer, run by Egetis Therapeutics AB (publ) at 33 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States, Bulgaria, Georgia, Sweden, Serbia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01619423, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2018.

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