Back to resultsAvastin and Chemotherapy Followed by a KRAS Stratified Randomization to Maintenance Treatment for First Line Treatment of Metastatic Colorectal Cancer. (ACT2)
Primary Purpose
Colorectal Cancer
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
bevacizumab, erlotinib
bevacizumab
bevacizumab
low dose capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring Untreated, First line, Chemotherapy, Maintenance treatment, KRAS wt, KRAS mutated, Anti-angiogenetic treatment, Metronomic capecitabine, bevacizumab, erlotinib, Translational research
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
Sites / Locations
- University Hospital
- County Hospital Ryhov
- County Hospital
- Central Hospital
- University Hospital
- Skåne University Hospital-Lund
- Karolinska University Hospital
- Sundsvall Hospital
- Norrland University Hospital
- Akademiska Hospital
- Central Hospital
- Central Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
bevacizumab and erlotinib (KRAS WT)
bevacizumab (KRAS WT)
bevacizumab (KRAS mutated)
low dose capecitabine (KRAS mutated)
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
To explore the activity of bevacizumab and low dose metronomic capecitabine in patients with KRAS mutated tumors.
Full Information
NCT ID
NCT01229813
First Posted
October 27, 2010
Last Updated
April 10, 2015
Sponsor
Lund University Hospital
Collaborators
Hoffmann-La Roche
1. Study Identification
Unique Protocol Identification Number
NCT01229813
Brief Title
Avastin and Chemotherapy Followed by a KRAS Stratified Randomization to Maintenance Treatment for First Line Treatment of Metastatic Colorectal Cancer.
Acronym
ACT2
Study Type
Interventional
2. Study Status
Record Verification Date
November 2013
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lund University Hospital
Collaborators
Hoffmann-La Roche
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
Untreated, First line, Chemotherapy, Maintenance treatment, KRAS wt, KRAS mutated, Anti-angiogenetic treatment, Metronomic capecitabine, bevacizumab, erlotinib, Translational research
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
233 (Actual)
8. Arms, Groups, and Interventions
Arm Title
bevacizumab and erlotinib (KRAS WT)
Arm Type
Active Comparator
Arm Title
bevacizumab (KRAS WT)
Arm Type
Active Comparator
Arm Title
bevacizumab (KRAS mutated)
Arm Type
Active Comparator
Arm Title
low dose capecitabine (KRAS mutated)
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
bevacizumab, erlotinib
Other Intervention Name(s)
Avastin, Tarceva
Intervention Description
bevacizumab 7.5 mg/kg body weight every third week, erlotinib 150 mg daily
Intervention Type
Drug
Intervention Name(s)
bevacizumab
Other Intervention Name(s)
Tarceva
Intervention Description
bevacizumab 7.5 mg/kg body weight every third week
Intervention Type
Drug
Intervention Name(s)
bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
bevacizumab 7.5 mg/kg body weight every third week.
Intervention Type
Drug
Intervention Name(s)
low dose capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
capecitabine 500 mg twice daily
Primary Outcome Measure Information:
Title
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.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
To explore the activity of bevacizumab and low dose metronomic capecitabine in patients with KRAS mutated tumors.
Time Frame
3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
University Hospital
City
Odense
Country
Denmark
Facility Name
County Hospital Ryhov
City
Jönköping
Country
Sweden
Facility Name
County Hospital
City
Kalmar
Country
Sweden
Facility Name
Central Hospital
City
Karlstad
Country
Sweden
Facility Name
University Hospital
City
Linköping
Country
Sweden
Facility Name
Skåne University Hospital-Lund
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
Facility Name
Karolinska University Hospital
City
Stockholm
Country
Sweden
Facility Name
Sundsvall Hospital
City
Sundsvall
Country
Sweden
Facility Name
Norrland University Hospital
City
Umeå
Country
Sweden
Facility Name
Akademiska Hospital
City
Uppsala
Country
Sweden
Facility Name
Central Hospital
City
Västerås
Country
Sweden
Facility Name
Central Hospital
City
Växjö
Country
Sweden
12. IPD Sharing Statement
Citations:
PubMed Identifier
26483047
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.
Results Reference
derived
Learn more about this trial
Avastin and Chemotherapy Followed by a KRAS Stratified Randomization to Maintenance Treatment for First Line Treatment of Metastatic Colorectal Cancer.
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