NCT02821559

Biweekly Versus Triweekly Raltitrexed With Oxaliplatin (With or Without Bevacizumab) in First-line Metastatic Colorectal Cancer

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 37 (actual)
• Sponsor: Centre Hospitalier Universitaire de Besancon · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Raltitrexed is a potent thymidylate synthase (TS) inhibitor. Conversely to 5-fluorouracil (5FU), raltitrexed can be administered safely in patients with cardiovascular disease, as well as in patients with dihydropyrimidine dehydrogenase deficit. Since raltitrexed is administered in 15-minutes infusion, complications related to continuous infusion can be avoided, and it becomes a potential good candidate for locoregional treatments as hepatic intra-arterial or intra-peritoneal infusion. Despite these potential benefits over 5FU, clinical trials failed in their temptation to replace the 5FU in colorectal cancer patients, mainly due to raltitrexed toxicity at 3mg/m2 every 3 weeks. Oxaliplatin has demonstrated a synergic effect when combined with TS inhibitors, and its association with raltitrexed was evaluated at 130mg/m2 of oxaliplatin and 3mg/m2 of raltitrexed, every 3 weeks. Actually, one of the first-line standard regimens in metastatic colorectal cancer patients is the biweekly FOLFOX (85mg/m2 of oxaliplatin, and infusional 5FU) plus bevacizumab regimen, since a significant progression-free survival (PFS) benefit was observed over FOLFOX plus placebo. Biweekly administration of raltitrexed at 2mg/m2 demonstrated a favorable toxicity profile even in patients aged \>65 years. Besides, the association of raltitrexed, oxaliplatin and bevacizumab seems safe. Then, the investigators decided to perform a randomized pharmacokinetic comparative study between biweekly TOMOX (raltitrexed 2 mg/m2 and oxaliplatin 85mg/m2) and triweekly TOMOX (raltitrexed 3 mg/m2 and oxaliplatin 130mg/m2) regimens in metastatic colorectal cancer patients, in a "ping-pong" crossover strategy to reduce the intra-individual variability. Bevacizumab was allowed at the dose of 5mg/kg or 7.5mg/kg, in biweekly and triweekly schedules, respectively. The secondary end-points were, objective response rate evaluated by RECIST 1.1 criteria, PFS, overall survival (OS), toxicity, and the comparison of toxicity between two arms for the first 2 cycles.

Conditions

• Metastatic Colorectal Cancer

Interventions

Type	Name	Description
DRUG	TOMOX
DRUG	Bevacizumab	Bevacizumab was allowed and used at 7,5 mg/kg or 5 mg/kg every 2 weeks.

Timeline

• Start date: 2012-07-01
• Primary completion: 2014-08-01
• First posted: 2016-07-01
• Last updated: 2016-07-01

Locations

1 site across 1 country: France