Metastatic Colorectal CancerPhase 2EROSNCT02821559
Biweekly Versus Triweekly Raltitrexed With Oxaliplatin (With or Without Bevacizumab) in First-line Metastatic Colorectal Cancer
A Phase 2 study testing TOMOX and Bevacizumab in people with Metastatic Colorectal Cancer, run by Centre Hospitalier Universitaire de Besancon at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- TOMOX and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteFrance
- Study dates
- 9 Aug 2012to 11 Sep 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
- Being tested
- TOMOX, Bevacizumab
- Keywords
- Colorectal cancer, raltitrexed, oxaliplatin, bevacizumab, biweekly, triweekly
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TOMOXDrug
Also called Tomudex-Oxaliplatin, Raltitrexed-Oxaliplatin
BevacizumabDrug
Bevacizumab was allowed and used at 7,5 mg/kg or 5 mg/kg every 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| triweekly then biweekly | Experimental | 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). Receives: Drug: TOMOX; Drug: Bevacizumab |
| biweekly then triweekly | Experimental | The arm B consisted of the reserve sequence starting with 2 cycles of biweekly TOMOX followed by 2 cycles of triweekly TOMOX regimen. Receives: Drug: TOMOX; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evolution of Raltitrexed plasma levels
pharmacokinetic study
Measured: at 5 minutes, at 40 minutes, at 2 hours, at 7,5 hours, at 24 hours and at 14 days after each raltitrexed administration
Secondary outcomes (4)
treatment-related adverse events as assessed by CTCAE v4.0
comparison of number of treatment-related adverse events between two arms
Measured: 3 months
objective response rate evaluated by RECIST 1.1 criteria
Measured: 3 months
progression-free survival (PFS)
from date to randomization to date of first progression of the disease
Measured: through study completion, an average of 2 years
overall survival (OS)
from date to randomization to date of death from any cause
Measured: through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2016 (estimated)
- Study start9 Aug 2012
- Primary completionAug 2014
- Study completion11 Sep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de BesanconThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Besancon
- Sponsor type
- University, hospital or other
- Collaborators
- Hospira, now a wholly owned subsidiary of Pfizer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02821559
- Sponsor's protocol ID
- EROS
- Other IDs
- 2011-005811-96
- Acronym
- EROS
- Status last verified
- Jul 2026
- First submitted
- 29 Mar 2016
- Last updated
- 23 Jul 2026
- Results posted
- No
Publications
Royer 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.
PubMed 32789966
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biweekly Versus Triweekly Raltitrexed With Oxaliplatin (With or Without Bevacizumab) in First-line Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT02821559
- Acronym / sponsor ID
- EROS / EROS
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Colorectal cancer, raltitrexed, oxaliplatin, bevacizumab, biweekly, triweekly
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de BesanconUniversity, hospital or other
- Collaborators
- Hospira, now a wholly owned subsidiary of Pfizer
- Study start
- 9 Aug 2012 (actual)
- Primary completion
- Aug 2014 (actual)
- Study completion
- 11 Sep 2014 (actual)
- First posted
- 1 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| triweekly then biweekly | Experimental | Drug: TOMOX, Drug: BevacizumabThe 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). |
| biweekly then triweekly | Experimental | Drug: TOMOX, Drug: BevacizumabThe arm B consisted of the reserve sequence starting with 2 cycles of biweekly TOMOX followed by 2 cycles of triweekly TOMOX regimen. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TOMOXAlso: Tomudex-Oxaliplatin, Raltitrexed-Oxaliplatin | Drug | biweekly then triweekly, triweekly then biweekly |
| BevacizumabBevacizumab was allowed and used at 7,5 mg/kg or 5 mg/kg every 2 weeks. | Drug | biweekly then triweekly, triweekly then biweekly |
Primary outcome
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
4 secondary outcomes
treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 3 months
objective response rate evaluated by RECIST 1.1 criteria
Time frame: 3 months
progression-free survival (PFS)
Time frame: through study completion, an average of 2 years
overall survival (OS)
Time frame: through study completion, an average of 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2026.
- Results publication: PubMed 32789966Royer 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TOMOX and Bevacizumab in people with Metastatic Colorectal Cancer, run by Centre Hospitalier Universitaire de Besancon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02821559, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2026.