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

NCT01229813 | Completed Phase 3

• 1 other identifier: ML 25359
• Study Type: interventional
• Target: 233
• Locations: 2 countries
• Sites: 12

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

Untreated; First line; Chemotherapy; Maintenance treatment; KRAS wt; KRAS mutated; Anti-angiogenetic treatment; Metronomic capecitabine; bevacizumab; erlotinib; Translational research

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• To explore the activity of bevacizumab and low dose metronomic capecitabine in patients with KRAS mutated tumors.

  3 years

Study Arms (4)

bevacizumab and erlotinib (KRAS WT)

ACTIVE COMPARATOR

Drug: bevacizumab, erlotinib

bevacizumab (KRAS WT)

ACTIVE COMPARATOR

Drug: bevacizumab

bevacizumab (KRAS mutated)

ACTIVE COMPARATOR

Drug: bevacizumab

low dose capecitabine (KRAS mutated)

ACTIVE COMPARATOR

Drug: low dose capecitabine

Interventions

bevacizumab, erlotinib DRUG

bevacizumab 7.5 mg/kg body weight every third week, erlotinib 150 mg daily

Also known as: Avastin, Tarceva

bevacizumab and erlotinib (KRAS WT)

bevacizumab DRUG

bevacizumab 7.5 mg/kg body weight every third week

Also known as: Tarceva

bevacizumab (KRAS WT)

low dose capecitabine DRUG

capecitabine 500 mg twice daily

Also known as: Xeloda

low dose capecitabine (KRAS mutated)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Lund University Hospital: lead
• Hoffmann-La Roche: collaborator

Study Sites (12)

University Hospital

Odense, Denmark

Location

County Hospital Ryhov

Jönköping, Sweden

Location

County Hospital

Kalmar, Sweden

Location

Central Hospital

Karlstad, Sweden

Location

University Hospital

Linköping, Sweden

Location

Skåne University Hospital-Lund

Lund, 221 85, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Sundsvall Hospital

Sundsvall, Sweden

Location

Norrland University Hospital

Umeå, Sweden

Location

Akademiska Hospital

Uppsala, Sweden

Location

Central Hospital

Vaxjo, Sweden

Location

Central Hospital

Västerås, Sweden

Location

Related Publications (1)

• 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.

  PMID: 26483047 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab; Erlotinib Hydrochloride; Capecitabine

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; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

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

Study Record Dates

• First Submitted: October 27, 2010
• First Posted: October 28, 2010
• Study Start: October 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: April 13, 2015

Record last verified: 2013-11

Locations

DK (1); SE (11)