Protective Effect of Mangafodipir Against Oxaliplatin Neurotoxicity (MnDPDP-K04)

November 17, 2025 updated by: Assistance Publique - Hôpitaux de Paris

Evaluation of Mangafodipir Protective Activity Against Oxaliplatin Neurotoxicity

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75014
        • COCHIN

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximal neuropathy severity (NCI-CTC score) established before each oxaliplatin injection
Time Frame: every 15 days
every 15 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of oxaliplatin administration
Time Frame: every 15 days
every 15 days
Progression free survival (time from inclusion to cancer progression)
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

URC-CIC Paris Descartes Necker Cochin

Investigators

  • Principal Investigator: Jerome Alexandre, MD, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2008

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

July 31, 2008

First Submitted That Met QC Criteria

August 1, 2008

First Posted (Estimated)

August 4, 2008

Study Record Updates

Last Update Posted (Actual)

November 20, 2025

Last Update Submitted That Met QC Criteria

November 17, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P071203

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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