study of e7070 combined with capecitabine to determine efficacy and recommended dose of combination in patients with metastatic colorectal cancer

Conditions: Colorectal Cancer (CRC)

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.


Eligibility 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 exclusion criteria: * prior chemotherapy other than 5-fu, irinotecan and/or oxaliplatin * 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 negative 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 start * 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