Colorectal cancer (advanced) Cancer Malignant neoplasm of other and ill-defined digestive organs
Conditions
Interventions
Amended 28/09/2010:
Patients will be recruited over 3 years and 6 months with 1 year follow up period.
Current information in October 2005:
1. Irinotec
Sponsors
University of Leeds (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current information as of 28/09/10: 1. Advanced colorectal cancer defined in either of the following ways: 1.1. Previous or current histologically confirmed primary adenocarcinoma of colon or rectum, together with clinical/radiological evidence of advanced/metastatic disease 1.2. Histologically/cytologically confirmed metastatic adenocarcinoma, together with clinical/radiological evidence of colorectal primary tumour 2. Unidimensionally measurable disease (please refer to RECIST criteria) 3. Prior fluoropyrimidine therapy, +/- oxaliplatin, +/- bevacizumab together with disease progression during or after that treatment. Adjuvant therapy and/or prior therapy for advanced disease may have been given 4. Able to start trial treatment within 14 days of randomisation 5. WHO performance status of 0, 1 or 2 and a life expectancy of at least 12 weeks 6. Aged =18 years at time of consent 7. Adequate full blood count, defined as: 7.1. Haemoglobin (Hb) >10.0 g/dl 7.2. While Blood Count (WBC) >3.0 x109/l 7.3. Platelets >100 x109/l 8. Adequate renal biochemistry, defined as: 8.1. Glomerular Filtration Rate (GFR) calculated/measured by either 8.1.1. Cockcroft formula >50 ml/min 8.1.2. EDTA clearance >60ml/min Or 8.2. Creatinine clearance measured by 24hr urine collection >60ml/min 9. Adequate hepatobiliary function 9.1. Total bilirubin < 25 umol/l 9.2. Alkaline Phosphatase (ALP) no more than 5x upper limit of normal (ULN) 9.3. Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) no more than 2.5 X ULN 9.4. No clinical or radiological evidence of biliary obstruction 9.5. No known history of Gilbert?s syndrome 10. If female and of child bearing potential, must have a negative pregnancy test within 72 hours before trial entry, is not breastfeeding and has agreed to take adequate, medically approved, contraceptive precautions (oral or barrier contraceptives under the supervision of a General Practioner or Family Planning Clinic) during and for 6 months after study treatment 11. If male with a partner of childbearing age, must agreed to use adequate, medically approved, contraceptive precautions (oral or barrier contraceptives under the supervision of a General Practioner or Family Planning Clinic) during and for 6 months after study treatment 12. Capable of reliable oral self-medication and toxicity reporting 13. Capable of completing Quality of Life questionnaires (The baseline Quality of Life questionnaire must be completed before randomisation) 14. In the opinion of the investigator: Is the patient capable of giving informed consent? Initial information at time of registration: 1. Confirmed advanced colorectal adenocarcinoma 2. Unidimensionally measurable disease (RECIST criteria) 3. Prior fluoropyrimidine +/- oxaliplatin therapy, +/- bevacizumab with disease progression during or after that treatment (adjuvant therapy and/or prior therapy for advanced disease may have been given) 4. At
Exclusion criteria
Exclusion criteria: Current information as of 28/09/10: 1. Previous treatment with irinotecan 2. Patient has received any of the following: 2.1. Capecitabine within 14 days prior to randomisation 2.2. All other licensed cytotoxic drugs within 21 days prior to randomisation 2.3. Prior cetuximab, panitumumab or bevacizumab within 21 days prior to randomisation 2.4. Any experimental anticancer drug therapy including antibodies within 42 days prior to randomisation 3. Prior anaphylactic allergic reaction to any anti-EGFR 4. Ongoing requirement for ciclosporin or any contraindicated concomitant medication, namely diltiazem, verapamil, amiodarone or fluvoxamine. Note: any prescribed short-courses of antifungals or antibiotics would not make a patient ineligible but should be completed 5 days before starting trial therapy. 5. Concurrent or previous other cancer (excluding non-melanomatous skin cancer), unresolved bowel obstruction or uncontrolled infection, uncontrolled chronic enteropathy (e.g. Crohn?s disease, ulcerative colitis), or chronic diarrhoea (=4 stools per day) of any cause 6. Major thoracic or abdominal surgery within the last 4 weeks 7. Known CNS metastases, carcinomatous meningitis or a recent history of seizures 8. Clinical/radiological evidence of interstitial pneumonitis, ulmonary fibrosis, pleural effusion or ascites causing grade =2 dyspnea 9. Any other condition, which, in the investigator?s opinion would make the patient unsuitable for participation in the trial Initial information at time of registration: 1. Any previous treatment with irinotecan 2. Experimental drug therapy or any antibody therapy other than cetuximab, within 6 weeks before study enrolment 3. Systemic chemotherapy and/or cetuximab within 28 days before study enrollment 4. Prior anaphylactic allergic reaction to cetuximab 5. Ongoing requirement for ciclosporin or any contraindicated concomitant medication, namely: diltiazem, verapamil, amiodarone or fluvoxamine 6. Concurrent or previous other cancer (excluding non-melanomatous skin cancer), major thoracic or abdominal surgery within preceding four weeks, unresolved bowel obstruction or uncontrolled infection, chronic enteropathy (e.g. Crohn?s disease, ulcerative colitis), or chronic diarrhoea (=4 stools per day) of any cause 7. Known CNS metastases, carcinomatous meningitis or recent history of seizures 8. Clinical or radiological evidence of interstitial pneumonitis, pulmonary fibrosis, pleural effusion or ascites causing grade =2 dyspnea 9. Incapable of reliable oral self-medication 10. Any other condition, which, in the investigator?s opinion would make the patient unsuitable for participation in the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ir vs IrCs comparison: proportion of patients progression-free 12 weeks after randomisation Amended 28/09/10: Ir vs IrPan comparison (patients with KRAS wildtype tumours not previously receiving an anti-EGRF targeted therapy cetuximab): overall survival (OS) from randomisation Initial information at time of registration: Ir vs IrPan comparison (patients not previously receiving cetuximab): overall survival (OS) from randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Current infotmation as of 28/09/10: Ir vs IrCs comparison: 1. Proportion of patients free from treatment failure at 12 weeks 2. Overall survival (OS) from randomisation 3. Research nurse-assessed toxicity (NCI-CTC[V3] grades): maximum toxicity grade per patient; rate per cycle; all-cause mortality within 60 days of randomisation; toxicity of primary interest is grade 3+ diarrhoea within 12 weeks of randomisation Ir vs IrPan comparison (patients with KRAS wildtype tumours not previously receiving an anti-EGRF targeted therapy): 1. Proportion of patients progression-free 12 weeks from randomisation 2. Research nurse-assessed toxicity (NCI-CTC[V3] grades): maximum toxicity grade per patient; rate per cycle; all-cause mortality within 60 days of randomisation Ir vs IrCs and Ir vs IrPan (patients with KRAS wildtype tumours not previously receiving an anti-EGRF targeted therapy) comparisons: 1. Progression-free survival (PFS) from randomisation 2. Best response by RECIST criteria at 1-year follow-up from randomisation 3. Patient-assessed symptom/QL/PA scores at 12 and 24 weeks Exploratory Endpoints Ir vs IrPan comparison (patients with KRAS wildtype tumours previously receiving an anti-EGRF targeted therapy): 1. Proportion of patients progression free 12 weeks after randomisation 2. Research nurse-assessed toxicity (NCI-CTC[V3] grades): maximum toxicity grade per patient; rate per cycle; all-cause mortality within 60 days of randomisation Ir vs IrPan comparison (patients randomised to receive Ir or IrPan under Protocol version 1.0 who have mutant or unknown KRAS status, regardless of previous anti-EGRF targeted therapy): 1. Proportion of patients progression free 12 weeks after randomisation | — |
Countries
United Kingdom
Outcome results
None listed