Biweekly Versus Triweekly Raltitrexed With Oxaliplatin (With or Without Bevacizumab) in First-line Metastatic Colorectal Cancer (EROS)
Primary Purpose
Metastatic Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
TOMOX
Bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Colorectal cancer, raltitrexed, oxaliplatin, bevacizumab, biweekly, triweekly
Eligibility Criteria
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
Sites / Locations
- CHRU de Besançon
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
triweekly then biweekly
biweekly then triweekly
Arm 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).
The arm B consisted of the reserve sequence starting with 2 cycles of biweekly TOMOX followed by 2 cycles of triweekly TOMOX regimen.
Outcomes
Primary Outcome Measures
Evolution of Raltitrexed plasma levels
pharmacokinetic study
Secondary Outcome Measures
treatment-related adverse events as assessed by CTCAE v4.0
comparison of number of treatment-related adverse events between two arms
objective response rate evaluated by RECIST 1.1 criteria
progression-free survival (PFS)
from date to randomization to date of first progression of the disease
overall survival (OS)
from date to randomization to date of death from any cause
Full Information
NCT ID
NCT02821559
First Posted
March 29, 2016
Last Updated
June 29, 2016
Sponsor
Centre Hospitalier Universitaire de Besancon
Collaborators
Hospira, now a wholly owned subsidiary of Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT02821559
Brief Title
Biweekly Versus Triweekly Raltitrexed With Oxaliplatin (With or Without Bevacizumab) in First-line Metastatic Colorectal Cancer
Acronym
EROS
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
July 2012 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Besancon
Collaborators
Hospira, now a wholly owned subsidiary of Pfizer
4. Oversight
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Colorectal cancer, raltitrexed, oxaliplatin, bevacizumab, biweekly, triweekly
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
triweekly then biweekly
Arm Type
Experimental
Arm 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).
Arm Title
biweekly then triweekly
Arm Type
Experimental
Arm Description
The arm B consisted of the reserve sequence starting with 2 cycles of biweekly TOMOX followed by 2 cycles of triweekly TOMOX regimen.
Intervention Type
Drug
Intervention Name(s)
TOMOX
Other Intervention Name(s)
Tomudex-Oxaliplatin, Raltitrexed-Oxaliplatin
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
Bevacizumab was allowed and used at 7,5 mg/kg or 5 mg/kg every 2 weeks.
Primary Outcome Measure Information:
Title
Evolution of Raltitrexed plasma levels
Description
pharmacokinetic study
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
Secondary Outcome Measure Information:
Title
treatment-related adverse events as assessed by CTCAE v4.0
Description
comparison of number of treatment-related adverse events between two arms
Time Frame
3 months
Title
objective response rate evaluated by RECIST 1.1 criteria
Time Frame
3 months
Title
progression-free survival (PFS)
Description
from date to randomization to date of first progression of the disease
Time Frame
through study completion, an average of 2 years
Title
overall survival (OS)
Description
from date to randomization to date of death from any cause
Time Frame
through study completion, an average of 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
CHRU de Besançon
City
Besançon
Country
France
12. IPD Sharing Statement
Learn more about this trial
Biweekly Versus Triweekly Raltitrexed With Oxaliplatin (With or Without Bevacizumab) in First-line Metastatic Colorectal Cancer
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