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

Colon Cancer Clinical Trial

— MANFOL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00671996
• Other study ID #: PP 01-07
• Status: Completed
• Phase: Phase 2
• First received: May 4, 2008
• Last updated: May 3, 2010
• Start date: June 2008
• Est. completion date: April 2010

Study information

• Verified date: May 2010
• Source: PledPharma AB
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chemotherapy
• Colon Cancer

Intervention

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.
• 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)

Locations

Country	Name	City	State
Sweden	Onkologkliniken, Länssjukhuset Ryhov	Jönköping

Sponsors (1)

Lead Sponsor	Collaborator
PledPharma AB

Country where clinical trial is conducted

Sweden, 

References & Publications (6)

Alexandre J, Nicco C, Chéreau 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neutropenia		Before and after completion of one, two and/or three FOLFOX6-cycles	No
Secondary	Quality of Life		Before and after completion of one, two and/or three FOLFOX6-cycles	No