Clinical trial NCT01229813: Avastin and Chemotherapy Followed by a KRAS Stratified Randomization to Maintenance Treatment for First Line Treatment of Metastatic Colorectal Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: Untreated
First line
Chemotherapy
Maintenance treatment
KRAS wt
KRAS mutated
Anti-angiogenetic treatment
Metronomic capecitabine
bevacizumab
erlotinib
Translational research
Lead sponsor: Lund University Hospital
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2010-10-28
Enrollment: 233
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: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 3 years
Secondary outcomes:
measure: To explore the activity of bevacizumab and low dose metronomic capecitabine in patients with KRAS mutated tumors.
timeFrame: 3 years
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: University Hospital
city: Jönköping
country: Sweden
facility: County Hospital Ryhov
city: Kalmar
country: Sweden
facility: County Hospital
city: Karlstad
country: Sweden
facility: Central Hospital
city: Linköping
country: Sweden
facility: University Hospital
city: Lund
country: Sweden
facility: Skåne University Hospital-Lund
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Sundsvall
country: Sweden
facility: Sundsvall Hospital
city: Umeå
country: Sweden
facility: Norrland University Hospital
city: Uppsala
country: Sweden
facility: Akademiska Hospital
city: Västerås
country: Sweden
facility: Central Hospital
city: Växjö
country: Sweden
facility: Central Hospital
Study officials:
References:
citation: 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.