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
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)