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

NCT ID: NCT01619423

Last Updated: 2018-07-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 186 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2016-12-31

Brief 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 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

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.

Conditions

Advanced Metastatic (Stage IV) Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

FOLFOX6 + PledOx 2 µmol/kg

PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

Group Type: ACTIVE_COMPARATOR

PledOx (2 µmol/kg)

Intervention Type: DRUG

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.

FOLFOX6 + PledOx 5 µmol/kg

PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

Group Type: ACTIVE_COMPARATOR

PledOx (5 µmol/kg)

Intervention Type: DRUG

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

FOLFOX6 + PledOx 10 µmol/kg

PledOx active ingredient= Calmangafodipir; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

Group Type: ACTIVE_COMPARATOR

PledOx (10 µmol/kg)

Intervention Type: DRUG

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

FOLFOX6 + 0,9% NaCl

Placebo= 0.9% NaCl; FOLFOX6=Combination of FOLinic Acid, 5-Fluorouracil (5-FU), and Oxaliplatin.

Group Type: PLACEBO_COMPARATOR

Placebo (0,9% NaCl)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Calmangafodipir; Calmangafodipir; Calmangafodipir; Sodium chloride

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharma Consulting Group AB

INDUSTRY

Sponsor Role: collaborator

Egetis Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marie Bengtson

Role: STUDY_DIRECTOR

Egetis Therapeutics

Locations

Moores UCSD Cancer Center

La Jolla, California, United States

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States

Associates in Oncology & Hematology

Chattanooga, Tennessee, United States

Wellmont Medical Associates Oncology and Hematology

Kingsport, Tennessee, United States

The University of Texas, Health Science Center at San Antonio

San Antonio, Texas, United States

Benaroya Research Institute @ Virginia Mason

Seattle, Washington, United States

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

Plovdiv, , Bulgaria

Complex Oncology Center-Shumen EOOD, Department of Medical Oncology

Shumen, , Bulgaria

MHAT "Serdika" EOOD, Department of Medical Oncology

Sofia, , Bulgaria

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

Sofia, , Bulgaria

SHATO EAD, Sofia, Clinic of Chemotherapy

Sofia, , Bulgaria

Aalborg University Hospital, Dept of Oncology, Clinical Research Unit

Aalborg, , Denmark

Odense Universitetshospital, Klinisk Forsknings Enhed, Onkologisk Afdelig R

Odense, , Denmark

LTD Clinic Medina

Batumi, , Georgia

Resaerch Institte of Clinical Medicine

Tbilisi, , Georgia

JSC "Neo Medi"

Tbilisi, , Georgia

LTD " High Technology Medical Center University Clinic"

Tbilisi, , Georgia

S. Khechinashvili University Hospital

Tbilisi, , Georgia

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

Bochum, , Germany

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

Dresden, , Germany

HELIOS Klinikum Wuppertal, Klinik für Hämatologie und Onkologie

Wuppertal, , Germany

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

Aveiro, , Portugal

Hospital de Braga, Oncologia Médica

Braga, , Portugal

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

Porto, , Portugal

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

Belgrade, , Serbia

Military Medical Academy, Gastroenterology department

Belgrade, , Serbia

Clinical Hospital Center Zemun, Insitute for Oncology

Belgrade, , Serbia

Clinical Center Kragujevac, Center for Oncology

Kragujevac, , Serbia

Gävle sjukhus, Oncology unit

Gävle, , Sweden

Sahlgrenska/Östra sjukhuset

Gothenburg, , Sweden

Universitetssjukhuset i Linköping

Linköping, , Sweden

Karolinska Sjukhuset

Stockholm, , Sweden

Akademiska Sjukhuset

Uppsala, , Sweden

Countries

United States; Bulgaria; Denmark; Georgia; Germany; Portugal; Serbia; Sweden

References

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.

Reference Type: RESULT

PMID: 29140155 (View on PubMed)

Other Identifiers

2012-001367-76

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PP095, (PLIANT)

Identifier Type: -

Identifier Source: org_study_id