Colorectal Cancer (CRC)
Conditions
Brief summary
Part 1: The primary purpose is to determine the recommended dose of E7070 in combination with capecitabine by dose adjustment. Part 2: The primary purpose is to determine the safety and efficacy of the combination in patients with metastatic CRC resistant to 5-fluorouracil and irinotecan.
Interventions
DRUGE7070
Sponsors
Eisai Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part 1 Inclusion Criteria: * Histologically or cytologically confirmed solid tumour refractory to standard therapy or for whom no established therapy exists * Age \>= 18 years * Karnofsky performance status of \>= 70% * Life expectancy of \>= 3 months * Absolute neutrophil count of \>= 1.5 × 109/l, platelet count of ³ 100 × 109/l, haemoglobin level of ³ 10 g/dl (\>= 6.2 mmol/l) (prior transfusion is permitted) * Normal hepatic and renal function as defined by serum bilirubin £ 1.5 times the upper limit of normal, ALT and AST £ 2.5 times the upper limit of normal (£ 5 times the upper limit of normal in the presence of hepatic metastases), creatinine clearance ³ 50 ml/min (by Cockroft-Gault formula) * Male and female patients * Written informed consent to participate in the study Part 1
Exclusion criteria
* More than two previous courses of documented myelosuppresive chemotherapy (epidermal growth factor targeted therapy does not constitute a course of chemotherapy) * CNS metastases (a CT or MRI scan should be done if there is a clinical suspicion of CNS metastases) * Major surgery, chemotherapy or radiation therapy (except palliative) within 4 weeks of treatment start * Previous investigational cytotoxic treatment for malignant disease within 30 days before the start of the study * Any treatment with non-oncological investigational drugs within 30 days before the start of the study * Pregnancy or breast feeding (all women of childbearing potential must have a pregnancy test before inclusion in the study; post-menopausal women must be amenorrhoeic for at least 12 months). Female patients must use adequate contraceptive protection. * Fertile males not willing to use contraception or whose female partners are not using adequate contraceptive protection * Uncontrolled infections * Clinically significant cardiac impairment or unstable ischaemic heart disease including a myocardial infarction within three months of study entry * History of alcoholism, drug addiction, or any psychiatric or psychological condition which in the opinion of the investigator would impair study compliance * History of hypersensitivity to sulphonamides * Prior severe or unexpected reaction to fluoropyrimidine therapy (which may be explained by dihydropyrimidine dehydrogenase deficiency or hypersensitivity to 5-FU) * Malabsorption syndrome or other condition which may affect absorption of drug * Concurrent or previous malignancy of a different tumour type within five years of starting the study except for adequately treated non-melanoma skin cancer or cervical intraepithelial neoplasia * Treatment within two weeks before the start of the study with any of the following: coumarin anti-coagulants, terfenadine, cisapride, cyclosporin, tacrolimus, theophylline, diazepam, sulphonylurea hypoglycaemics, phenytoin, or carbamazepine * Legal incapacity Part 2 Inclusion Criteria: * Ambulant patients with progressive metastatic CRC who have received prior treatment with 5 FU and irinotecan and/or oxaliplatin either as single agents or in combination. Either 5 FU and/or irinotecan and/or oxaliplatin may have been administered in the adjuvant setting or for the treatment of metastatic disease. Patients who have received both 5-FU and irinotecan or oxaliplatin in the adjuvant setting only must have experienced disease recurrence within one year of starting chemotherapy. * At least one unidimensionally measurable lesion according to the RECIST criteria * Age ³ 18 years * Karnofsky performance status of ³ 70% * Life expectancy of ³ 3 months * Absolute neutrophil count of ³ 1.5 × 109/l, platelet count of ³ 100 × 109/l, haemoglobin level of ³ 10 g/dl (³ 6.2 mmol/l) (prior transfusion is permitted) * Normal hepatic and renal function as defined by serum bilirubin £ 1.5 times the upper limit of normal, ALT and AST £ 2.5 times the upper limit of normal (£ 5 times the upper limit of normal in the presence of hepatic metastases), creatinine clearance ³ 50 ml/min (by Cockroft-Gault formula) * Male and female patients * Written informed consent to participate in the study Part 2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the recommended dose of E7070 in combination with capecitabine by dose adjustment; | — |
| to determine the safety, tolerability and efficacy (in terms of response rate and progression-free survival) of the combination in patients with metastatic CRC. | — |
Secondary
| Measure | Time frame |
|---|---|
| Determine the pharmacokinetic profile of capecitabine and E7070 when administered in combination; | — |
| measure duration of response and stable disease; to measure median and one year survival. | — |
Countries
France, Germany, Netherlands
Outcome results
None listed