Patient with metastatic colorectal cancer MedDRA version: 12.0 Level: LLT Classification code 10010029 Term: Colorectal cancer NOS
Conditions
Interventions
Trade Name: Afinitor
Pharmaceutical Form: Tablet
CAS Number: 159351-69-6
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 7.5-10
Sponsors
Department of OncologyHerlev University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Criteria for inclusion: 1. Patients with a histological or cytological verified adenocarcinoma of the colon or rectum with non-resectable or metastatic cancer. 2. Patients with measurable disease without previous radiotherapy according to RECIST criteria. 3. Patients with metastatic colorectal cancer with progression after previous therapy with 5-fluoropyrimidiner, oxaliplatin or irinotecan. Patients should have been treated with oxaliplatin, but if oxaliplatin has be contraindicated or not tolerated the patient can participate in the trial. 4. Patients with KRAS mutation in their primary tumour or metastasis. 5. Patients with progression after therpay with irinotecan or cetuximab undependent of KRAS mutation status. . 6. Previous radiotherapy is allowed to less than 25 % of the bone marrow. 7. Age more or equal to 18 years. 8. Performance status (WHO) less than 3. 9. An expected survival time of at least 3 months. 10. Absolute Neutrophil Count (ANC) ?1,5 x 109/l and trombocyt count =100 x 109/l. 11. Normal liver function with bilirubin =1,5 x UNL (upper normal limit) og ASAT/ALAT =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Criterai for exclusion: 1. Former or other concurrent malignant disease exept treated basal cell carcinoma or in situ cervical cancer. 2. No cytotoxic therapy or other experimental treatment within 28 days before inclusion. 3. No former therapy with everolimus or other rapamyciner (sirolimus, temsirolimus). 4. No known hypersensitivity for one or more components in the therapy. 5. No uncontrolled diabetes defined as a fasting blod sucker > 1.5 x ULN (upper normal limit). 6. No serious non-healing wounds, gastic ulcers, bonefractures, greater surgical procedures, major traumatic injuries within 28 days before inclusion. 7. No ungoing bleading or pathological condition associated with a risk of bleading. 8. No liverdisease as cirrhose, chronical active hepatitis or chronic persistent hepatitis. 9. No gastrointestinal disturbences in function that might cause a major change in the absortion of everolimus as ulcerative disease, ucontrolled nausea, vomiting, diarrhoe, malabsorption syndrom. 10. No planned immunisation with attenuated virus in the study period. 11. Patients thjat is unable to follow treatment or evaluation plan. 12. Every condition or therapy that after the judgement of investigator might infer the patient a risk or influence the trials objective. 13. Pregnant or breastfeeding women. At fertile women this is insured by a negative test of pregnancy or use of a safe antikonception during the trial period and at least 3 months after end of treatment. 14. Patients with active infections or other serious medical co-morbidity, that might prevent the patient from being treated with the protocoled therapy. 15. Incapacitated,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Main objective: • Disease control as the sum of number of patients with CR, PR and SD. ;Secondary Objective: • TTP. • Lenght of disease control. • Survival • Safety and toxicity • Influence of smoking on disease control, response and survial time to progression. • Significance of metabolic responce evaluated by a PET/CT scan. • Blood: Examine the influence of potentiel predictive and prognostic tumour biomarcers in blood as LDH, CEA, VEGF, EGFR, HER-2, YKL-40, IL-6, TIMP-1, P1NP, P3NP, gen-, microRNA- and proteinarray profiles, metabolomics and CRP 2 weeks after start of therapy and thereafter every 8.weeks on disease control, response, survival and time to progression and other parameters investigated. •Tissue: Examine possible predictive and prognostic biomarkers in tissue from primary tumour or metastases for microRNAarray profiles, mutations in K-RAS, BRAF, PIK3CA, EGFR, p53, and protein ekspression and polymorphisms of PTEN, EREG, AREG, IGF-1, IGF-1R, VEGF, p53, Topo1, YKL-40, and TIMP-1 •Correlation between possible predictive and prognostic biomarkers. ;Primary end point(s): Disease control as sum of number of patients with CR, PR, and SD | — |
Countries
Denmark
Outcome results
None listed