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Completed

NCT Number: NCT02821559

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

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.

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Key information

Conditions

Metastatic Colorectal Cancer Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

CHRU de Besançon

Besançon, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

TOMOX

Drug

Other names: Tomudex-Oxaliplatin, Raltitrexed-Oxaliplatin

Bevacizumab

Drug

Bevacizumab was allowed and used at 7,5 mg/kg or 5 mg/kg every 2 weeks.

Primary outcomes

  1. Evolution of Raltitrexed plasma levels

    Time frame: at 5 minutes, at 40 minutes, at 2 hours, at 7,5 hours, at 24 hours and at 14 days after each raltitrexed administration

    pharmacokinetic study

Secondary outcomes

  1. treatment-related adverse events as assessed by CTCAE v4.0

    Time frame: 3 months

    comparison of number of treatment-related adverse events between two arms

  2. objective response rate evaluated by RECIST 1.1 criteria

    Time frame: 3 months

  3. progression-free survival (PFS)

    Time frame: through study completion, an average of 2 years

    from date to randomization to date of first progression of the disease

  4. overall survival (OS)

    Time frame: through study completion, an average of 2 years

    from date to randomization to date of death from any cause

Sponsors and collaborators

Lead sponsor

Centre Hospitalier Universitaire de Besancon

Other

Collaborators

  • Hospira, now a wholly owned subsidiary of Pfizer

Registry information

Acronym: EROS

Important dates

Study start
2012
Primary completion
2014
Study completion
2014
First posted
Jul 1, 2016
Registry last updated
Jul 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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