Metastatic Colorectal Cancer
Conditions
Keywords
Unresectable metastases
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
Interventions
DRUGbevacizumab, oxaliplatin and 5FU combination
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)
DRUGBevacizumab, oxaliplatin and raltitrexed combination
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
Sponsors
Institut du Cancer de Montpellier - Val d'Aurelle
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free survival | 6 months | DFS is estimated from the date of randomization until the first date of objectively documented event or death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-related toxicity | 6 months | Treatment-related toxicity is evaluated according to the NCI-CTCAE v.4 criteria. |
| Objective response rate | Every 9 weeks | Objective response rate is evaluated according to the RECIST V 1.1 criteria. |
| Overall survival | unk | OS is estimated from the date of randomization until the date of death from any cause |
| Cost-effectiveness study | 6 months | 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 | 6 months | Quality of life is measured using the QLQ-C30 questionnaire |
Countries
France
Outcome results
None listed