Mangafodipir as an Adjunct to FOLFOX6 Chemotherapy in Colon Cancer Stage Dukes' C

Study Overview
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Brief Summary
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The present feasibility study is designed to find out whether pre-treatment with the compound mangafodipir lowers the frequency and severity of side effects during adjuvant chemotherapy according to the FOLFOX6 regimen in patients operated upon colon cancer in stage Dukes' C.

Detailed Description
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Mangafodipir, manganese (Mn) dipyridoxyl diphosphate, is a catalytic antioxidant and iron chelator recently (2006) suggested for cancer treatment in an Editorial in Journal of the National Cancer Institute. Preclinical research has shown that mangafodipir protects normal tissues without loss of anti-tumour activity during chemotherapy. Other advantages are that mangafodipir is already approved for use in patients as a contrast agent for magnetic resonance imaging (MRI) of liver, and that the experience for more than a decade reveals high safety with mainly minor and tolerable side-effects. The present study will include 14 patients who will be followed throughout 3 treatment cycles. Each cycle will be preceded by infusion of mangafodipir or placebo in two groups, each consisting of 7 patients. The primary endpoints will be the most frequent manifestation of FOLFOX6, namely neutropenia and neurosensory toxicity. The secondary endpoints will be the frequency and severity of other FOLFOX6-related adverse events and quality of life.

Official Title
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A Local Feasibility Study on Mangafodipir as an Adjunct to FOLFOX6 Chemotherapy in Patients Operated Upon Colon Cancer Stage Dukes' C

Conditions
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Chemotherapy, Colon Cancer

Intervention / Treatment
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* Drug: Mangafodipir
* Drug: Placebo treatment (0.9% NaCl)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven colon cancer stage Dukes' C. Patient over 18 years. WHO performance status <1. Adequate haematological function (Hb ≥ 100 g/L, ANC ≥ 2.0 x 109/L, platelets ≥ 150 x 109/L) Adequate renal and hepatic functions: serum creatinine and total bilirubin ≤ 1.25 times upper normal limits (ASAT and ALAT ≤ 3 times upper normal limits) Clinical evaluation, haematology and biochemistry performed within 1 week prior to the start of chemotherapy Use of adequate contraception (males with reproductive potential) Written informed consent given Exclusion Criteria: Other tumour types than colon adenocarcinomas Current severe neutropenia, leucopenia or thrombocytopenia Severely reduced liver or renal function Unresolved bowel obstruction or sub-obstruction, uncontrolled Crohn's disease or ulcerative colitis Current chronic diarrhoea Contraindication for corticosteroid administration History of prior serious allergic or pseudo-allergic reaction Any other serious illness or medical condition Symptomatic peripheral neuropathy ≥ grade 2 Received mangafodipir ≤ 5 weeks before planned start of chemotherapy Received any of the FOLFOX drugs ≤ 5 weeks before planned start of chemotherapy Any plans of administered other anti-cancer therapy (including radiotherapy) concurrent with this study Fertile females Males with reproductive potential not implementing adequate contraception measures Phaeochromocytoma

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Mangafodipir treatment | Drug: Mangafodipir<br>* Treatment will be undertaken with a ready-to-use investigative drug formulation identical to what is in diagnostic use as a contrast medium for MRI. Formulation content: MnDPDP 10 mmol/ml Administered dose per cycle: 2 μmol/kg b.w. Administration form: Ready-to-use formulation (solution). Mangafodipir or placebo (0.2 ml/kg b.w.) will be administered as an i.v. infusion over 5 min about 30 min prior to start of chemotherapy.<br>* Other names: Teslascan; ACT code V08CAE05;|
| Placebo Comparator: B<br> | Drug: Placebo treatment (0.9% NaCl)<br>* Intravenous infusion, 2 micromol/kg, pretreatment 30 minutes before the start of FOLFOX treatment (during the first three FOLFOX treatments)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutropenia |  | Before and after completion of one, two and/or three FOLFOX6-cycles | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life |  | Before and after completion of one, two and/or three FOLFOX6-cycles |