|- candidate number||7844|
|- NTR Number||NTR2245|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||17-mrt-2010|
|- Secondary IDs||2010-019005-41 Eudractnumber|
|- Public Title||Effects of Cimetidine on Cisplatin-induced Nephrotoxicity.|
|- Scientific Title||Effects of Cimetidine on Cisplatin-induced Nephrotoxicity.|
|- hypothesis||The nephrotoxicity caused by cisplatin is of great concern both in that it is dose-limiting and can be detrimental to the patient. Much work has been done to reduce or prevent this damage to renal cells, however to date the best approach has reduced the occurance but not completely prevented it. Most approaches to date have involved diluting the concentration of cisplatin (via longer infusion rate, intravenous hydration, and concomitant mannitol), which has reduced the toxicity somewhat but has failed to prevent it. There is a growing body of evidence that the renal cell damage is localized on the basolateral side of the proximal tubular cells. The presence of a cisplatin transporting solute carrier (OCT2 in humans and Oct1/2 in rodents) on the basolateral side of the proximal tubular cells is a likely candidate for how cisplatin enters the renal cells. Instead of attempting to dilute the circulating concentration of cisplatin, we propose that by blocking the OCT2-mediated uptake of cisplatin we may be able to prevent the nephrotoxicity from occurring.|
|- Healt Condition(s) or Problem(s) studied||Cisplatin, Irresectable head and neck cancer, Metastatic head and neck cancer|
|- Inclusion criteria||1. Histological or cytological confirmed diagnosis of any form of irresectable and/or metastatic Head and Neck cancer, which is not currently being treated with cisplatin;|
2. Treatment with high doses of cisplatin (3-weekly 100 mg/m2), with radiotherapy. No other systemic anti-cancer treatment is allowed;
3. Age > 18 years;
4. WHO performance < 1;
5. Adequate hematological functions (ANC > 1.5 x 109/L, platelets > 100 x 1012/L);
6. Adequate renal and hepatic functions (serum creatinin < 1.25xULN, bilirubin < 1.25xULN, ALAT and ASAT < 2.5xULN, in case of liver metastasis < 5 ULN; alkaline phosphatase < 5xULN);
7. Written informed consent;
8. Complete initial work-up within four weeks prior to therapy with cisplatin or the combination of cisplatin and cimetidine.
|- Exclusion criteria||1. Pregnant or lactating patients; patients with reproductive potential must use a reliable method of contraception (excluding oral contraceptives), if required;|
2. Serious illness or medical unstable condition requiring treatment, symptomatic CNS-metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent;
3. Current use of cisplatin therapy;
4. Patients with Chronic Kidney Disease;
5. Major surgery within 4 weeks before start of the protocol (to be evaluated by an MD);
6. (Chronic) use of CYP3A and/or ABCB1/ABCG2 inhibiting and inducing medication, dietary supplements, or other inhibiting compounds (see Appendix D);
7. Unwillingness to change medication, or no adequate alternatives available, when drugs are taken that are known to interact with CYP3A and/or ABCB1 and/or ABCG2;
8. Use of cimetidine 4 weeks prior to study entry.
|- mec approval received||no|
|- multicenter trial||no|
|- control||Not applicable|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-mei-2010|
|- planned closingdate||1-nov-2011|
|- Target number of participants||20|
|- Interventions||In a counterbalanced design half of the patients will receive concomitant administration of cimetidine with their cisplatin on the initial day of treatment and no cimetidine on the second day of treatment (3 weeks later), and vice versa for the other half of the patients. |
|- Primary outcome||To investigate the ability of cimetidine to prevent cisplatin-induced nephrotoxicity, while not impairing the efficacy of cisplatin in Head and Neck cancer patients.|
Urine and blood work will be done to establish baseline kidney function/damage.
|- Secondary outcome||N/A|
|- Timepoints||Study plan: |
Day -1: Informed consent, check of inclusion/exclusion criteria, and registration. Urine and blood work to establish baseline kidney function/damage and collection of blood for subsequent genotyping of patients.
Day 1: Administration of cimetidine to ½ of group. Initiation of cisplatin treatment. Urine and blood samples take over 24 hours.
Day 7: Urine and blood work to establish baseline kidney function/damage.
Day 14: Urine and blood work to establish baseline kidney function/damage.
Day 21: Urine and blood work to establish baseline kidney function/damage. Administration of cimetidine to the other half of group. 2nd cycle of cisplatin treatment. Urine and blood samples taken over 24 hours.
Dat 28: Urine and blood work to establish baseline kidney function/damage.
Day 35: Urine and blood work to establish baseline kidney function/damage.
|- Trial web site||N/A|
|- status||stopped: trial finished|
|- CONTACT FOR PUBLIC QUERIES||MD L. Gerven, van|
|- CONTACT for SCIENTIFIC QUERIES||MD PhD Ron H.J. Mathijssen|
|- Sponsor/Initiator ||Erasmus Medical Center, Daniel den Hoed Cancer Center |
(Source(s) of Monetary or Material Support)
|- Publications||Sprowl et al. Conjunctive therapy of cisplatin with the OCT2 inhibitor cimetidine: influence on antitumor efficacy and systemic clearance. Clin Pharmacol Ther 2013;94(5):585-92|
|- Brief summary||N/A|
|- Main changes (audit trail)|
|- RECORD||17-mrt-2010 - 12-okt-2016|