Avastin and Chemotherapy Followed by a KRAS Stratified Randomization to Maintenance Treatment for First Line Treatment of Metastatic Colorectal Cancer. (ACT2)

Patients with metastatic colorectal cancer will be treated with chemotherapy according to investigators choice. In addition to chemotherapy treatment, treatment with bevacizumab will be given concomitantly. This treatment will continue during 18 weeks. Meanwhile, the patients KRAS status will be tested. After having fulfilled these 18 weeks of induction treatment, patients who has responded (complete response/partial response versus stable disease) will be randomized to maintenance treatment. Patients with KRAS WT will be randomized to either bevacizumab alone, or to bevacizumab and erlotinib. Patient with KRAS mutation will be randomized to either bevacizumab, or metronomic capecitabine. Translational research is performed, with purpose to find predictive factors in blood and tumor tissue.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: bevacizumab, erlotinib; Drug: bevacizumab; Drug: bevacizumab; Drug: low dose capecitabine

• Study Type: Interventional
• Enrollment (Actual): 233
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark
    • University Hospital
• Sweden
  • Jönköping, Sweden
    • County Hospital Ryhov
  • Kalmar, Sweden
    • County Hospital
  • Karlstad, Sweden
    • Central Hospital
  • Linköping, Sweden
    • University Hospital
  • Lund, Sweden, 221 85
    • Skåne University Hospital-Lund
  • Stockholm, Sweden
    • Karolinska University Hospital
  • Sundsvall, Sweden
    • Sundsvall Hospital
  • Umeå, Sweden
    • Norrland University Hospital
  • Uppsala, Sweden
    • Akademiska hospital
  • Västerås, Sweden
    • Central Hospital
  • Växjö, Sweden
    • Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Untreated metastatic colorectal carcinoma
• Age 18 yrs or over
• Measurable disease according to Response Evaluation Criteria in solid Tumors (RECIST criteria)
• ECOG performance status 0 or 1
• Life expectancy more than 3 months
• Adequate haematological, renal and liver function
• Tumor tissue available for determination of KRAS mutational status
• Blood sample and paraffin embedded tumor tissue for translational research

Exclusion Criteria:

• Adjuvant therapy within 6 months
• CNS metastases
• Clinically significant atherosclerotic vascular disease

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: bevacizumab and erlotinib (KRAS WT)	Drug: bevacizumab, erlotinib; bevacizumab 7.5 mg/kg body weight every third week, erlotinib 150 mg daily; Other Names: Avastin, Tarceva
Active Comparator: bevacizumab (KRAS WT)	Drug: bevacizumab; bevacizumab 7.5 mg/kg body weight every third week; Other Names: Tarceva; Drug: bevacizumab; bevacizumab 7.5 mg/kg body weight every third week.; Other Names: Avastin
Active Comparator: bevacizumab (KRAS mutated)	Drug: bevacizumab; bevacizumab 7.5 mg/kg body weight every third week; Other Names: Tarceva; Drug: bevacizumab; bevacizumab 7.5 mg/kg body weight every third week.; Other Names: Avastin
Active Comparator: low dose capecitabine (KRAS mutated)	Drug: low dose capecitabine; capecitabine 500 mg twice daily; Other Names: Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To demonstrate that maintenance treatment with bevacizumab + erlotinib following first line chemo- and anti-angiogenetic therapy results in a significant increase in progression free survival (PFS) compared to treatment with only bevacizumab.	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To explore the activity of bevacizumab and low dose metronomic capecitabine in patients with KRAS mutated tumors.	3 years

Collaborators and Investigators

• Sponsor: Lund University Hospital
• Collaborators: Hoffmann-La Roche

Publications and helpful links

General Publications

• Hagman H, Frodin JE, Berglund A, Sundberg J, Vestermark LW, Albertsson M, Fernebro E, Johnsson A. A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer: the Nordic ACT2 trial. Ann Oncol. 2016 Jan;27(1):140-7. doi: 10.1093/annonc/mdv490. Epub 2015 Oct 19.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: October 27, 2010
• First Submitted That Met QC Criteria: October 27, 2010
• First Posted (Estimate): October 28, 2010

Study Record Updates

• Last Update Posted (Estimate): April 13, 2015
• Last Update Submitted That Met QC Criteria: April 10, 2015
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Maintenance treatment; bevacizumab; erlotinib; Chemotherapy; Untreated; First line; Translational research; KRAS wt; KRAS mutated; Anti-angiogenetic treatment; Metronomic capecitabine
• 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; Protein Kinase Inhibitors; Erlotinib Hydrochloride; Capecitabine; Bevacizumab
• Other Study ID Numbers: ML 25359