Protective Effect of Mangafodipir Against Oxaliplatin Neurotoxicity

Cancer Clinical Trial

— MnDPDP-K04  

Official title:

Evaluation of Mangafodipir Protective Activity Against Oxaliplatin Neurotoxicity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00727922
• Other study ID #: P071203
• Status: Completed
• Phase: Phase 2
• First received: July 31, 2008
• Last updated: December 15, 2011
• Start date: June 2008
• Est. completion date: April 2011

Study information

• Verified date: July 2011
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Oxaliplatin is a major antitumor agent but its use is limited by potentially disabling neurotoxicity, characterized by a sensitive defect in the extremities.Mangafodipir is a MRI contrast agent with antioxidant properties. Our previous laboratory works showed that mangafodipir is able to prevent hematologic toxicity of several chemotherapy agents, including oxaliplatin and to increase their antitumor activity. Preliminary clinical data suggested that mangafodipir could prevent oxaliplatin neurotoxicity.The primary purpose of the present study is to assess the protective effect of mangafodipir in patients who have a already moderate oxaliplatin neuropathy and in whom the continuation of this treatment is desirable because of significant antitumor effect.

Description:

Phase 2 study aiming to assess the protective effect of mangafodipir against the oxaliplatine neuropathy.Population: Cancer patient who have a mild (grade 2) oxaliplatin neuropathy and in whom the continuation of oxaliplatin for at least 4 infusions is desirable will be include, whatever the location of the primitive tumor and the use of others anticancer agents.Treatment: Mangafodipir (0.5 ml/kg) is administered as a 30 minutes infusion just after each administration of oxaliplatin. The oxaliplatin dose (85 to 100 mg/m²) and the length of the infusion (2 hours) are the same that before the inclusion and modifications are not authorized during all the study participation. Primary objective: Neuropathy are clinically evaluated according to NCI-CTC criteria before each mangafodipir and oxaliplatin and thereafter one month after the last infusion. The primary criteria is the worst grade of oxaliplatin neuropathy experienced by each patient. The improvement of neuropathy is defined as a decrease by at least one grade of the severity of the neuropathy for at least 2 months.

Hypothesis: at least 50% of patients will experience an improvement or a stabilization of the oxaliplatin neuropathy while receiving the mangafodipir - oxaliplatin association.Treatment discontinuation: the treatment will be stopped if the neuropathy worsened by at least one grade, in case of tumor progression, intolerable toxicity, and patient wish.

Number of patients: it will be determined according to a simplified Gehan procedure: The inclusions will be stopped if no objective response (neuropathy improvement) is observed among the first 9 evaluable patients. If at least one response is observed, 16 more evaluable patients will be include. The total number of patients will be between 9 and 30 patients, including non evaluable patients.

Pharmacokinetic: Serum and intra- erythrocytes manganese concentration will be evaluated before each mangafodipir infusion in order to detect accumulation Pharmacodynamic: plasmatic total antioxidant activity, superoxide dismutase activity and lipid peroxidation will be assessed at the first cycle: before and after the administration of oxaliplatin and just after the perfusion of mangafodipir.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: April 2011
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• NCI CTC grade 2 or more neuropathy induced by oxaliplatine

• At least 18 years old

• ECOG PS: 2 or less

• Life expectancy longer than 3 months

• Written informed consent

• Adequate hematologic, liver and renal functions

Exclusion Criteria:

• Known hypersensibility to oxaliplatine

• Cancer resistant to oxaliplatine

• Fertile woman or man not willing to use adequate contraception

• Pregnant or lactating women

• Vitamin B6 administration within 48h prior to mangafodipir administration

• Uncontrolled infection

• Treatment with any other investigational agent, or participation in another clinical trial within 3 weeks prior to first administration of mangafodipir

• Evidence of any other disease or condition that contra-indicates the use of an investigational drug

• No Social Security insurance

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer
• Neurotoxic Disorders
• Neurotoxicity Syndromes

Intervention

Drug:
• Mangafodipir
Mangafodipir (0.5 ml/kg) is administered as a 30 minutes infusion just after each administration of oxaliplatin. The oxaliplatin dose (85 to 100 mg/m²) and the length of the infusion (2 hours) are the same that before the inclusion and modifications are not authorized during all the study participation. During 4 months (8 administrations).

Locations

Country	Name	City	State
France	Cochin	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximal neuropathy severity (NCI-CTC score) established before each oxaliplatin injection		every 15 days	No
Secondary	Number of oxaliplatin administration		every 15 days	No
Secondary	Progression free survival (time from inclusion to cancer progression)		6 months	No