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

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

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.

Study Overview

• Status: Completed
• Conditions: Chemotherapy; Colon Cancer
• Intervention / Treatment: Drug: Mangafodipir; Drug: Placebo treatment (0.9% NaCl)

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Jönköping, Sweden, SE-551 85
    • Onkologkliniken, Länssjukhuset Ryhov

Participation Criteria

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:

1. Histologically proven colon cancer stage Dukes' C.
2. Patient over 18 years.
3. WHO performance status <1.
4. Adequate haematological function (Hb ≥ 100 g/L, ANC ≥ 2.0 x 109/L, platelets ≥ 150 x 109/L)
5. Adequate renal and hepatic functions: serum creatinine and total bilirubin ≤ 1.25 times upper normal limits (ASAT and ALAT ≤ 3 times upper normal limits)
6. Clinical evaluation, haematology and biochemistry performed within 1 week prior to the start of chemotherapy
7. Use of adequate contraception (males with reproductive potential)
8. Written informed consent given

Exclusion Criteria:

1. Other tumour types than colon adenocarcinomas
2. Current severe neutropenia, leucopenia or thrombocytopenia
3. Severely reduced liver or renal function
4. Unresolved bowel obstruction or sub-obstruction, uncontrolled Crohn's disease or ulcerative colitis
5. Current chronic diarrhoea
6. Contraindication for corticosteroid administration
7. History of prior serious allergic or pseudo-allergic reaction
8. Any other serious illness or medical condition
9. Symptomatic peripheral neuropathy ≥ grade 2
10. Received mangafodipir ≤ 5 weeks before planned start of chemotherapy
11. Received any of the FOLFOX drugs ≤ 5 weeks before planned start of chemotherapy
12. Any plans of administered other anti-cancer therapy (including radiotherapy) concurrent with this study
13. Fertile females
14. Males with reproductive potential not implementing adequate contraception measures
15. Phaeochromocytoma

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: B	Drug: Placebo treatment (0.9% NaCl); Intravenous infusion, 2 micromol/kg, pretreatment 30 minutes before the start of FOLFOX treatment (during the first three FOLFOX treatments)
Active Comparator: A; Mangafodipir treatment	Drug: Mangafodipir; 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.; Other Names: Teslascan; ACT code V08CAE05

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Egetis Therapeutics
• Investigators: Principal Investigator: Ursula Falkmer, MD, PhD, Lanssjukhuset Ryhov

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: May 4, 2008
• First Submitted That Met QC Criteria: May 4, 2008
• First Posted (Estimate): May 6, 2008

Study Record Updates

• Last Update Posted (Estimate): May 4, 2010
• Last Update Submitted That Met QC Criteria: May 3, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: PP 01-07