A Study of Avastin (Bevacizumab) in Combination With mFOLFOX6 in Treatment-Naïve Patients With Metastatic Colorectal Cancer With or Without K-RAS Mutations, and Comparison to Cetuximab

NCT01338558 | Withdrawn Phase 3

• 1 other identifier: ML25686
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This randomized, open-label study will evaluate the safety and efficacy of Avastin (Bevacizumab) added to standard mFOLFOX6 chemotherapy in treatment-naïve patients with Stage IV metastatic colorectal cancer. According to K-RAS gene mutation status, patients will be assigned or randomized to receive either Avastin 5 mg/kg intravenously (iv) on Day 1 of each 2-week cycle or cetuximab 400 mg/m2 iv on Day 1 followed by 250 mg/m2 iv every week, in addition to mFOLFOX6 every 2 weeks. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free survival: native versus mutated K-RAS; tumour assessments according to RECIST criteria

  up to 4 years

Secondary Outcomes (5)

• Overall survival

  up to 4 years

• Objective response rate

  4 years

• Safety: Incidence of adverse events

  4 years

• Quality of Life: European Organisation for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30)

  up to 4 years

• Progression-free survival: comparison of the two treatment regimens in the native K-RAS arms

  up to 4 years

Study Arms (3)

K-RAS mutated

EXPERIMENTAL

Drug: bevacizumab [Avastin]; Drug: mFOLFOX6

K-RAS native A

EXPERIMENTAL

Drug: bevacizumab [Avastin]; Drug: mFOLFOX6

K-RAS native B

ACTIVE COMPARATOR

Drug: cetuximab; Drug: mFOLFOX6

Interventions

bevacizumab [Avastin] DRUG

5 mg/kg iv on Day 1 of each 2-week cycle until disease progression, unacceptable toxicity or withdrawal of consent

K-RAS mutated; K-RAS native A

cetuximab DRUG

400 mg /m2 iv on Day 1, followed by 250 mg/m2 every week until disease progression, unacceptable toxicity or withdrawal of consent

K-RAS native B

mFOLFOX6 DRUG

Standard mFOLFOX6 chemotherapy, 2-week cycles until disease progression, unacceptable toxicity or withdrawal of consent

K-RAS mutated; K-RAS native A; K-RAS native B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients \>/= 18 years of age
• Histologically confirmed adenocarcinoma of the colon or rectum
• Stage IV metastatic disease with at least one measurable metastatic lesion according to RECIST criteria
• Tumour tissue sample available for assessment of K-RAS and BRAF genes
• Prior radiotherapy must have been completed 4 weeks before randomization
• Adequate bone marrow, kidney and liver function
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

You may not qualify if:

• Previous chemotherapy for metastatic disease
• Completion of adjuvant treatment for colorectal cancer (Stage I, II and III) in the 12 months preceding randomization
• Prior treatment with bevacizumab, cetuximab or other EGFR inhibitors
• Clinical or radiographic evidence of brain metastases
• Clinically significant cardiovascular disease or disorder
• History of neoplastic disease other than colorectal cancer in the 3 years prior to start of study treatment, except for successfully treated non-invasive carcinomas such as cervical cancer in situ, basal cell carcinoma of the skin or superficial bladder tumours
• HIV, hepatitis B or C infection

Sponsors & Collaborators

• Hoffmann-La Roche: lead

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab; Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2011
• First Posted: April 19, 2011
• Study Start: June 1, 2011
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: November 2, 2016

Record last verified: 2016-11