Clinical trial · Interventional
Biweekly Versus Triweekly Raltitrexed With Oxaliplatin (With or Without Bevacizumab) in First-line Metastatic Colorectal Cancer
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Metastatic Colorectal Cancer | Malignant Colorectal Neoplasm | CURATED_BROADER | 0.80 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Bevacizumab | Drug | Bevacizumab | ALIAS |
| TOMOX | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- triweekly then biweekly
- description
- The arm A consisted of 2 cycles of triweekly TOMOX (standard dose 3mg/m2 of Raltitrexed in 15-minutes infusion, and 130mg/m2 of oxaliplatin in 2h infusion, every 3 weeks), followed by 2 cycles of biweekly TOMOX (2mg/m2 of Raltitrexed in 15-minutes infusion, and 85mg/m2 of oxaliplatin in 2h infusion, every 2 weeks).
- interventionNames
- Drug: TOMOX
- Drug: Bevacizumab
- type
- EXPERIMENTAL
- label
- biweekly then triweekly
- description
- The arm B consisted of the reserve sequence starting with 2 cycles of biweekly TOMOX followed by 2 cycles of triweekly TOMOX regimen.
- interventionNames
- Drug: TOMOX
- Drug: Bevacizumab
Primary outcomes (1)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 80 Years
Show eligibility criteria text
Inclusion Criteria: * performance status (ECOG-PS) of 0 or 1 * patient with histologically proven colorectal cancer with distant metastases * measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 * life expectancy \> 12 months * signed written informed consent Exclusion Criteria: * prior chemotherapy at metastatic stage * presence of brain or meningeal metastases * other malignancies in the past 5 years with the exception of adequately treated carcinoma in situ of the cervix and squamous or basal cell carcinoma of the skin * preexisting peripheral neuropathy * known hypersensitivity to any component of the study treatment * any psychiatric condition compromising the understanding of information or conduct of the study * pregnancy, breast-feeding or absence of adequate contraception for fertile patients * patient under guardianship, curator or under the protection of justice
References
Publications (1)
- RESULTRoyer B, Schmitt A, Nguyen T, Paillard MJ, Jary M, Demarchi M, Vernerey D, Henriques J, Jacquin M, Borg C, Kim S. Exposure-response analysis of Raltitrexed assessing liver toxicity. Br J Clin Pharmacol. 2021 Mar;87(3):1327-1337. doi: 10.1111/bcp.14519. Epub 2020 Sep 4. PMID 32789966