2nd-line Treatment of Metastatic Colorectal Cancer (BEVATOMOX)

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

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: bevacizumab, oxaliplatin and 5FU combination; Drug: Bevacizumab, oxaliplatin and raltitrexed combination

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

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34298
    • Val d'Aurelle Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; FOLFOX6 + bevacizumab (D1=D15, 12 cycles)	Drug: bevacizumab, 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)
Experimental: Arm B; Raltitrexed + Oxaliplatin + Bevacizumab (D1=D21, 8 cycles)	Drug: Bevacizumab, 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	DFS is estimated from the date of randomization until the first date of objectively documented event or death	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-related toxicity	Treatment-related toxicity is evaluated according to the NCI-CTCAE v.4 criteria.	6 months
Objective response rate	Objective response rate is evaluated according to the RECIST V 1.1 criteria.	Every 9 weeks
Overall survival	OS is estimated from the date of randomization until the date of death from any cause	unk
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	6 months
Quality of life by using the quality of life questionnaire score	Quality of life is measured using the QLQ-C30 questionnaire	6 months

Collaborators and Investigators

• Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
• Investigators: Principal Investigator: Emmanuelle Samalin-Scalzi, MD, Val d'Aurelle Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2011
• Primary Completion (Actual): May 12, 2016
• Study Completion (Actual): January 1, 2019

Study Registration Dates

• First Submitted: February 10, 2012
• First Submitted That Met QC Criteria: February 14, 2012
• First Posted (Estimate): February 15, 2012

Study Record Updates

• Last Update Posted (Actual): December 26, 2019
• Last Update Submitted That Met QC Criteria: December 24, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Unresectable metastases
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Folic Acid Antagonists; Oxaliplatin; Bevacizumab; Raltitrexed
• Other Study ID Numbers: BEVATOMOX; 2010-023447-15 (EudraCT Number)