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

NCT00671996 | Completed Phase 2

• 1 other identifier: PP 01-07
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Chemotherapy; Colon Cancer

Outcome Measures

Primary Outcomes (1)

• Neutropenia

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

Secondary Outcomes (1)

• Quality of Life

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

Study Arms (2)

A

ACTIVE COMPARATOR

Mangafodipir treatment

Drug: Mangafodipir

B

PLACEBO COMPARATOR

Drug: Placebo treatment (0.9% NaCl)

Interventions

Mangafodipir DRUG

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.

Also known as: Teslascan; ACT code V08CAE05

A

Placebo treatment (0.9% NaCl) DRUG

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

B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Egetis Therapeutics: lead

Study Sites (1)

Onkologkliniken, Länssjukhuset Ryhov

Jönköping, SE-551 85, Sweden

Location

Related Publications (6)

• 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.

  PMID: 16478742 BACKGROUND

• 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.

  PMID: 7965775 BACKGROUND

• 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.

  PMID: 9920816 BACKGROUND

• 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.

  PMID: 16478735 BACKGROUND

• 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.

  PMID: 11736698 BACKGROUND

• 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.

  PMID: 16397277 BACKGROUND

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Ursula Falkmer, MD, PhD

  Länssjukhuset Ryhov

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 4, 2008
• First Posted: May 6, 2008
• Study Start: June 1, 2008
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: May 4, 2010

Record last verified: 2010-05

Locations

SE (1)