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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00727922
Recruitment Status : Completed
First Posted : August 4, 2008
Last Update Posted : December 16, 2011
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief 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.

Condition or disease Intervention/treatment Phase
Neurotoxic Disorders Cancer Drug: Mangafodipir Phase 2

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 Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Mangafodipir Protective Activity Against Oxaliplatin Neurotoxicity
Study Start Date : June 2008
Primary Completion Date : January 2010
Study Completion Date : April 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Oxaliplatin
U.S. FDA Resources

Arms and Interventions

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).


Outcome Measures

Primary Outcome Measures :
  1. Maximal neuropathy severity (NCI-CTC score) established before each oxaliplatin injection [ Time Frame: every 15 days ]

Secondary Outcome Measures :
  1. Number of oxaliplatin administration [ Time Frame: every 15 days ]
  2. Progression free survival (time from inclusion to cancer progression) [ Time Frame: 6 months ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00727922


Locations
France
Cochin
Paris, France, 75014
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Jerome Alexandre, MD, PhD Assistance Publique - Hôpitaux de Paris
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00727922     History of Changes
Other Study ID Numbers: P071203
First Posted: August 4, 2008    Key Record Dates
Last Update Posted: December 16, 2011
Last Verified: July 2011

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Neuropathy
Oxaliplatin
Mangafodipir

Additional relevant MeSH terms:
Neurotoxicity Syndromes
Nervous System Diseases
Poisoning
Chemically-Induced Disorders
Oxaliplatin
Edetic Acid
Pyridoxal Phosphate
Antineoplastic Agents
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs