Effects of mutations in KRAS and BRAF gene and histological parameters on the clinical course of disease in patients with metastatic colorectal cancer

ISRCTN	ISRCTN10604174
DOI	https://doi.org/10.1186/ISRCTN10604174
Secondary identifying numbers	105/08/10

Submission date: 04/11/2010
Registration date: 20/12/2010
Last edited: 12/02/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

Not provided at time of registration

Contact information

Dr Martina Rebersek
Scientific

Zaloska 2
Ljubljana
1000
Slovenia

Study information

Study design	Single centre prospective cohort study
Primary study design	Interventional
Secondary study design	Cohort study
Study setting(s)	Hospital
Study type	Diagnostic
Participant information sheet	Not available in web format, please use contact details below to request a patient information sheet
Scientific title	The influence of mutation status in KRAS and BRAF gene according to the classical histological parameters of tumor as a predictive factor of the aggressive course of disease in metastatic colorectal cancer: a single centre, prospective, cohort trial
Study hypothesis	Knowledge of mutation status of KRAS and BRAF genes in addition to classical prognostic factors (histological characteristics of tumor and number of affected regional lymph nodes) improves the prediction of the aggressive course of disease in metastatic colorectal cancer to determine the start and the type of systemic therapy.
Ethics approval(s)	The National Medical Ethics Committee, Ministry of Health, Republic of Slovenia, approved on the 26th August 2010 (ref: 105/08/10)
Condition	Metastatic colorectal cancer
Intervention	Patients with metastatic colorectal adenocarcinoma will be treated with combination chemotherapy and targeted drugs in accordance with the guidelines for the systemic treatment of metastatic colorectal carcinoma and reviewed in accordance with good clinical practice and recommendations. The efficacy of treatment will be assessed in terms of RECIST criteria (version 1.1, Eur J Cancer 2009). During the treatment toxicity will be recorded according the Common Terminology Criteria for Adverse Events (CTCAE), version 4.02. In histological preparations, we will search for radical resection, the presence of vascular and perinevral invasion, lymphatic invasion, stage T, differentiation of tumor, number of affected regional lymph nodes. Molecular analysis for the presence of mutations in KRAS and BRAF gene we will do on the existing primary tumor or metastases, or in bioptic samples of primary tumor or metastases.
Intervention type	Other
Primary outcome measure	1. Progression-free survival (PFS) 2. Response rate (Response Evaluation Criteria in Solid Tumors [RECIST]) in correlation with histological parameters of tumor tissue, KRAS and BRAF status
Secondary outcome measures	Overall survival (OS)
Overall study start date	29/11/2010
Overall study end date	31/12/2013

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	400 patients
Participant inclusion criteria	1. Written informed consent 2. Histologically confirmed colorectal cancer 3. Diagnosis of metastatic disease 4. Age 18 to 75 years 5. Eastern Cooperative Oncology Group (ECOG) performance score 0 - 2 6. Life expectancy of at least 3 months 7. Primary tumor with described histological features 8. Histology available for further analysis and molecular diagnostics 9. Determination of BRAF mutations in KRAS gene before starting treatment 10. Adequate haematological function (ANC greater than or equal to 1.5 x 10/9L, platelets greater than or equal to 100 x 10/9/L, Hb greater than or equal to 90 g/L) 11. Adequate liver function (serum bilirubin less than or equal to 1.5 x ULN, AST/ALP less than or equal to 2.5 x ULN 12. In case of liver metastases less than 5 x ULN), adequate renal function (calculated creatinine clearance greater than or equal to 50 mL/min)
Participant exclusion criteria	1. ECOG performance score greater than 2 2. Participation in another clinical trial within 30 days prior to entering this study 3. Known hypersensitivity to any of the study drugs 4. Clinically significant cardiovascular disease (myocardial infarction less than or equal to 6 months before treatment start 5. Unstable angina 6. Uncontrolled hypertension 7. Arrhythmia requiring medication 8. Clinically significant renal disease (creatinine clearance less than 30 ml/min) 9. Liver cirrhosis Child B and C 10. Psychiatric disability to be clinically significant precluding informed consent 11. Evidence of any other disease 12. Metabolic dysfunction or laboratory findings, which give a suspicion of a disease or condition that contraindicates the use of any investigational drugs or means a higher risk for treatment-related complications
Recruitment start date	29/11/2010
Recruitment end date	31/12/2013

Locations

Countries of recruitment

Slovenia

Study participating centre

Zaloska 2

Ljubljana
1000
Slovenia

Sponsor information

Institute of Oncology Ljubljana (Slovenia)
Research organisation

Zaloska 2
Ljubljana
1000
Slovenia

Phone	+38 (0)61 5879220
Email	mrebersek@onko-i.si
"ROR"	https://ror.org/00y5zsg21

Funders

Funder type

Research organisation

Institute of Oncology Ljubljana (Slovenia)

No information available

Results and Publications

Intention to publish date	01/03/2019
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	The article will be published in March 2019.
IPD sharing plan

Editorial Notes

12/02/2019: The publication and dissemination plan and intention to publish date were added.