Protective Effect of Mangafodipir Against Oxaliplatin Neurotoxicity
Sleutelwoorden
Abstract
Omschrijving
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.
Datums
| Laatst geverifieerd: | 06/30/2011 |
| Eerste ingediend: | 07/30/2008 |
| Geschatte inschrijving ingediend: | 07/31/2008 |
| Eerst geplaatst: | 08/03/2008 |
| Laatste update ingediend: | 12/14/2011 |
| Laatste update geplaatst: | 12/15/2011 |
| Werkelijke startdatum van het onderzoek: | 05/31/2008 |
| Geschatte primaire voltooiingsdatum: | 12/31/2009 |
| Geschatte voltooiingsdatum van het onderzoek: | 03/31/2011 |
Conditie of ziekte
Interventie / behandeling
Drug: 1
Fase
Armgroepen
| Arm | Interventie / behandeling |
|---|---|
| Experimental: 1 | Drug: 1 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). |
Geschiktheidscriteria
| Leeftijden die in aanmerking komen voor studie | 18 Years Naar 18 Years |
| Geslachten die in aanmerking komen voor studie | All |
| Accepteert gezonde vrijwilligers | Ja |
| 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 |
Resultaat
Primaire uitkomstmaten
1. Maximal neuropathy severity (NCI-CTC score) established before each oxaliplatin injection [every 15 days]
Secundaire uitkomstmaten
1. Number of oxaliplatin administration [every 15 days]
2. Progression free survival (time from inclusion to cancer progression) [6 months]
