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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00727922
First received: July 31, 2008
Last updated: December 15, 2011
Last verified: July 2011
  Purpose

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 Intervention Phase
Neurotoxic Disorders
Cancer
Drug: Mangafodipir
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Mangafodipir Protective Activity Against Oxaliplatin Neurotoxicity

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Maximal neuropathy severity (NCI-CTC score) established before each oxaliplatin injection [ Time Frame: every 15 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of oxaliplatin administration [ Time Frame: every 15 days ] [ Designated as safety issue: No ]
  • Progression free survival (time from inclusion to cancer progression) [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 23
Study Start Date: June 2008
Study Completion Date: April 2011
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
Other Name: Mangafodipir

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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

No publications provided by Assistance Publique - Hôpitaux de Paris

Additional 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
Study First Received: July 31, 2008
Last Updated: December 15, 2011
Health Authority: France: Ministry of Health

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

Additional relevant MeSH terms:
Neurotoxicity Syndromes
Nervous System Diseases
Poisoning
Chemically-Induced Disorders
N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid
Edetic Acid
Pyridoxal Phosphate
Oxaliplatin
Contrast Media
Diagnostic Uses of Chemicals
Pharmacologic Actions
Anticoagulants
Hematologic Agents
Therapeutic Uses
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 20, 2014