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

Primary Purpose

Chemotherapy, Colon Cancer

Status

Completed

Phase

Phase 2

Locations

Sweden

Study Type

Interventional

Intervention

Mangafodipir

Placebo treatment (0.9% NaCl)

About this trial

This is an interventional treatment trial for Chemotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Onkologkliniken, Länssjukhuset Ryhov

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Arm Description

Mangafodipir treatment

Outcomes

Primary Outcome Measures

Neutropenia

Secondary Outcome Measures

Quality of Life

Full Information

NCT ID

NCT00671996

First Posted

May 4, 2008

Last Updated

May 3, 2010

Sponsor

Egetis Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT00671996

Brief Title

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

Acronym

MANFOL

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2010

Overall Recruitment Status

Completed

Study Start Date

June 2008 (undefined)

Primary Completion Date

April 2010 (Actual)

Study Completion Date

April 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Egetis Therapeutics

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chemotherapy, Colon Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

Mangafodipir treatment

Arm Title

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Mangafodipir

Other Intervention Name(s)

Teslascan; ACT code V08CAE05

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo treatment (0.9% NaCl)

Intervention Description

Intravenous infusion, 2 micromol/kg, pretreatment 30 minutes before the start of FOLFOX treatment (during the first three FOLFOX treatments)

Primary Outcome Measure Information:

Title

Neutropenia

Time Frame

Before and after completion of one, two and/or three FOLFOX6-cycles

Secondary Outcome Measure Information:

Title

Quality of Life

Time Frame

Before and after completion of one, two and/or three FOLFOX6-cycles

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ursula Falkmer, MD, PhD

Organizational Affiliation

Länssjukhuset Ryhov

Official's Role

Principal Investigator

Facility Information:

Facility Name

Onkologkliniken, Länssjukhuset Ryhov

City

Jönköping

ZIP/Postal Code

SE-551 85

Country

Sweden

12. IPD Sharing Statement

Citations:

PubMed Identifier

16478742

Citation

Alexandre J, Nicco C, Chereau C, Laurent A, Weill B, Goldwasser F, Batteux F. Improvement of the therapeutic index of anticancer drugs by the superoxide dismutase mimic mangafodipir. J Natl Cancer Inst. 2006 Feb 15;98(4):236-44. doi: 10.1093/jnci/djj049.

Results Reference

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PubMed Identifier

7965775

Citation

Asplund A, Grant D, Karlsson JO. Mangafodipir (MnDPDP)-and MnCl2-induced endothelium-dependent relaxation in bovine mesenteric arteries. J Pharmacol Exp Ther. 1994 Nov;271(2):609-14.

Results Reference

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PubMed Identifier

9920816

Citation

Brurok H, Ardenkjaer-Larsen JH, Hansson G, Skarra S, Berg K, Karlsson JO, Laursen I, Jynge P. Manganese dipyridoxyl diphosphate: MRI contrast agent with antioxidative and cardioprotective properties? Biochem Biophys Res Commun. 1999 Jan 27;254(3):768-72. doi: 10.1006/bbrc.1998.0131.

Results Reference

background

PubMed Identifier

16478735

Citation

Doroshow JH. Redox modulation of chemotherapy-induced tumor cell killing and normal tissue toxicity. J Natl Cancer Inst. 2006 Feb 15;98(4):223-5. doi: 10.1093/jnci/djj065. No abstract available.

Results Reference

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PubMed Identifier

11736698

Citation

Karlsson JO, Brurok H, Eriksen M, Towart R, Toft KG, Moen O, Engebretsen B, Jynge P, Refsum H. Cardioprotective effects of the MR contrast agent MnDPDP and its metabolite MnPLED upon reperfusion of the ischemic porcine myocardium. Acta Radiol. 2001 Nov;42(6):540-7. doi: 10.1080/028418501127347340.

Results Reference

background

PubMed Identifier

16397277

Citation

Karlsson JO, Brurok H, Towart R, Jynge P. The magnetic resonance imaging contrast agent mangafodipir exerts antitumor activity via a previously described superoxide dismutase mimetic activity. Cancer Res. 2006 Jan 1;66(1):598; author reply 598. doi: 10.1158/0008-5472.CAN-05-2053. No abstract available.

Results Reference

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

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