Clinical trial NCT01532804: 2nd-line Treatment of Metastatic Colorectal Cancer
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Unresectable metastases
Lead sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
Sponsor class: OTHER
First posted: 2012-02-15
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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)

Primary outcomes:
measure: Disease-free survival
timeFrame: 6 months
Secondary outcomes:
measure: Treatment-related toxicity
timeFrame: 6 months
measure: Objective response rate
timeFrame: Every 9 weeks
measure: Overall survival
timeFrame: unk
measure: Cost-effectiveness study
timeFrame: 6 months
measure: Quality of life by using the quality of life questionnaire score
timeFrame: 6 months
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Val d'Aurelle Cancer Institute
Study officials:
affiliation: Val d'Aurelle Cancer Institute
name: Emmanuelle Samalin-Scalzi, MD
role: PRINCIPAL_INVESTIGATOR
References: