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

Egetis Therapeutics

Status and phase: Completed; Phase 2

Conditions: Chemotherapy; Colon Cancer

Treatments: Drug: Placebo treatment (0.9% NaCl); Drug: Mangafodipir

Study type: Interventional

Funder types: Industry

Identifiers

NCT00671996

PP 01-07

Details and patient eligibility

About

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.

Full 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.

Enrollment: 14 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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14 participants in 2 patient groups, including a placebo group

A

Active Comparator group

Description:

Mangafodipir treatment

Treatment:

Drug: Mangafodipir

B

Placebo Comparator group

Treatment:

Drug: Placebo treatment (0.9% NaCl)