2nd-line Treatment of Metastatic Colorectal Cancer (BEVATOMOX)
Primary Purpose
Metastatic Colorectal Cancer
Status
Terminated
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
bevacizumab, oxaliplatin and 5FU combination
Bevacizumab, oxaliplatin and raltitrexed combination
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Unresectable metastases
Eligibility Criteria
Inclusion Criteria:
- Histologically proven colorectal cancer
- Resected or asymptomatic primary tumor
- Metastatic colorectal cancer not eligible for curative surgery
- No major surgery within four weeks of the start of study treatment
- At least one target lesion unidimensionally measurable on cross-sectional imaging according to RECIST criteria (v1.1)
- Disease progression after failure of irinotecan-based chemotherapy
- Bone metastases are allowed if there is at least one other measurable metastatic site
- CT scan of the abdomen, chest and pelvis within 3 weeks of the start of study treatment
- WHO PS ≤ 2
- Platelet count >= 100,000 mm3
- Hemoglobin > 10g/dl
- Bilirubin < 1.5 ULN, AST/ALT < 5 ULN
- Serum creatinine < 1.5 ULN, creatinine clearance > 60 ml/min (Cockcroft)
- A time period of 4 weeks should be respected between the end of previous treatments and study enrollment
- Negative pregnancy test in women of childbearing potential
- Male or female using an effective contraceptive method
- Absence of known or symptomatic brain metastases
- Life expectancy > 3 months
- Informed consent signed prior any study specific procedures
Exclusion Criteria:
- Prior raltitrexed-based chemotherapy
- Prior oxaliplatin-based chemotherapy (except for adjuvant treatment completed for more than 6 months)
- Uncontrolled arterial hypertension defined as systolic pressure > 150 mm Hg or diastolic pressure > 100 mm Hg
- Malignant hypertension or hypertensive encephalopathy
- Myocardial infarction, pulmonary embolism, or severe vascular disease within 6 months prior to study entry
- Hemorrhagic diathesis or significant pathology of coagulation
- Peripheral neuropathy grade>2 (NCI-CTC v4.0)
- Hemoptysis < 1 month
- Venous access device (PAC) or any other minor surgery such as a biopsy within the last 7 days
- Symptomatic brain metastases or carcinomatous meningitis
- History or presence of other cancer within the past 5 years (except curatively treated nonmelanoma skin cancer and in situ cervical cancer)
- Severe bacterial or fungal infection (Grade > 2 NCI-CTCAE v.4.0)
- Known or suspected sensitivity to one of the study drugs
- Pregnant or breastfeeding women
- Previous enrollment in an investigational drug study within the last 4 weeks
- Psychological, social, geographical disorders or any other condition that would preclude study compliance (treatment administration and study follow-up)
Sites / Locations
- Val d'Aurelle Cancer Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm A
Arm B
Arm Description
FOLFOX6 + bevacizumab (D1=D15, 12 cycles)
Raltitrexed + Oxaliplatin + Bevacizumab (D1=D21, 8 cycles)
Outcomes
Primary Outcome Measures
Disease-free survival
DFS is estimated from the date of randomization until the first date of objectively documented event or death
Secondary Outcome Measures
Treatment-related toxicity
Treatment-related toxicity is evaluated according to the NCI-CTCAE v.4 criteria.
Objective response rate
Objective response rate is evaluated according to the RECIST V 1.1 criteria.
Overall survival
OS is estimated from the date of randomization until the date of death from any cause
Cost-effectiveness study
The cost-effectiveness study includes the number of hospital stays (treatment and toxicity), the global cost of treatments, and the cost of hospital stays due to treatment-induced toxicity
Quality of life by using the quality of life questionnaire score
Quality of life is measured using the QLQ-C30 questionnaire
Full Information
NCT ID
NCT01532804
First Posted
February 10, 2012
Last Updated
December 24, 2019
Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle
1. Study Identification
Unique Protocol Identification Number
NCT01532804
Brief Title
2nd-line Treatment of Metastatic Colorectal Cancer
Acronym
BEVATOMOX
Official Title
A Multicenter Randomized Phase 2 Trial to Evaluate the Triplet Combination of Raltitrexed, Oxaliplatin and Bevacizumab Versus FOLFOX6 Plus Bevacizumab in Second-line Treatment of Metastatic Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Terminated
Why Stopped
too slow recruiting
Study Start Date
July 28, 2011 (Actual)
Primary Completion Date
May 12, 2016 (Actual)
Study Completion Date
January 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut du Cancer de Montpellier - Val d'Aurelle
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This phase 2 trial aims to evaluate the continued use of bevacizumab with raltitrexed and oxaliplatin combination versus FOLFOX6 plus bevacizumab in patients with metastatic colorectal cancer whose disease has progressed after irinotecan-based chemotherapy.
Detailed Description
Eligible patients are randomly allocated to receive either bevacizumab with raltitrexed and oxaliplatin combination or bevacizumab with FOLFOX 6 combination. Random allocation schedule is performed using a minimization technique for the following stratification factors:
Center
Number of metastatic sites: 1 versus > 1
Bevacizumab-based first-line therapy: Yes versus No
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Unresectable metastases
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
83 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Experimental
Arm Description
FOLFOX6 + bevacizumab (D1=D15, 12 cycles)
Arm Title
Arm B
Arm Type
Experimental
Arm Description
Raltitrexed + Oxaliplatin + Bevacizumab (D1=D21, 8 cycles)
Intervention Type
Drug
Intervention Name(s)
bevacizumab, oxaliplatin and 5FU combination
Intervention Description
Bevacizumab 5 mg/kg administered as an iv infusion for 1h30, then for 1h and for 30 min. at the following cycles, respectively.
Oxaliplatin 85 mg/m² administered as an iv infusion for 2h Elvorine 200 mg/m² administered as an iv infusion for 2h 5FU 400 mg/m2 bolus then 5FU 2,400 mg/m² iv infusion for 46h D1=D15 (12 cycles)
Intervention Type
Drug
Intervention Name(s)
Bevacizumab, oxaliplatin and raltitrexed combination
Intervention Description
Bevacizumab 7.5 mg/kg administered as an iv infusion for 1h30, then administered for 1h and 30 min at the following cycles, respectively.
Oxaliplatin 130 mg/m² administered as an iv infusion for 2h Raltitrexed 3 mg/m² administered as an iv infusion for 15 min
Primary Outcome Measure Information:
Title
Disease-free survival
Description
DFS is estimated from the date of randomization until the first date of objectively documented event or death
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Treatment-related toxicity
Description
Treatment-related toxicity is evaluated according to the NCI-CTCAE v.4 criteria.
Time Frame
6 months
Title
Objective response rate
Description
Objective response rate is evaluated according to the RECIST V 1.1 criteria.
Time Frame
Every 9 weeks
Title
Overall survival
Description
OS is estimated from the date of randomization until the date of death from any cause
Time Frame
unk
Title
Cost-effectiveness study
Description
The cost-effectiveness study includes the number of hospital stays (treatment and toxicity), the global cost of treatments, and the cost of hospital stays due to treatment-induced toxicity
Time Frame
6 months
Title
Quality of life by using the quality of life questionnaire score
Description
Quality of life is measured using the QLQ-C30 questionnaire
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically proven colorectal cancer
Resected or asymptomatic primary tumor
Metastatic colorectal cancer not eligible for curative surgery
No major surgery within four weeks of the start of study treatment
At least one target lesion unidimensionally measurable on cross-sectional imaging according to RECIST criteria (v1.1)
Disease progression after failure of irinotecan-based chemotherapy
Bone metastases are allowed if there is at least one other measurable metastatic site
CT scan of the abdomen, chest and pelvis within 3 weeks of the start of study treatment
WHO PS ≤ 2
Platelet count >= 100,000 mm3
Hemoglobin > 10g/dl
Bilirubin < 1.5 ULN, AST/ALT < 5 ULN
Serum creatinine < 1.5 ULN, creatinine clearance > 60 ml/min (Cockcroft)
A time period of 4 weeks should be respected between the end of previous treatments and study enrollment
Negative pregnancy test in women of childbearing potential
Male or female using an effective contraceptive method
Absence of known or symptomatic brain metastases
Life expectancy > 3 months
Informed consent signed prior any study specific procedures
Exclusion Criteria:
Prior raltitrexed-based chemotherapy
Prior oxaliplatin-based chemotherapy (except for adjuvant treatment completed for more than 6 months)
Uncontrolled arterial hypertension defined as systolic pressure > 150 mm Hg or diastolic pressure > 100 mm Hg
Malignant hypertension or hypertensive encephalopathy
Myocardial infarction, pulmonary embolism, or severe vascular disease within 6 months prior to study entry
Hemorrhagic diathesis or significant pathology of coagulation
Peripheral neuropathy grade>2 (NCI-CTC v4.0)
Hemoptysis < 1 month
Venous access device (PAC) or any other minor surgery such as a biopsy within the last 7 days
Symptomatic brain metastases or carcinomatous meningitis
History or presence of other cancer within the past 5 years (except curatively treated nonmelanoma skin cancer and in situ cervical cancer)
Severe bacterial or fungal infection (Grade > 2 NCI-CTCAE v.4.0)
Known or suspected sensitivity to one of the study drugs
Pregnant or breastfeeding women
Previous enrollment in an investigational drug study within the last 4 weeks
Psychological, social, geographical disorders or any other condition that would preclude study compliance (treatment administration and study follow-up)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emmanuelle Samalin-Scalzi, MD
Organizational Affiliation
Val d'Aurelle Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Val d'Aurelle Cancer Institute
City
Montpellier
ZIP/Postal Code
34298
Country
France
12. IPD Sharing Statement
Learn more about this trial
2nd-line Treatment of Metastatic Colorectal Cancer
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