Study of E7070 Combined With Capecitabine to Determine Efficacy and Recommended Dose of Combination in Patients With Metastatic Colorectal Cancer

Eisai

Status and phase

Completed

Phase 2

Conditions

Colorectal Cancer (CRC)

Treatments

Drug: E7070

Study type

Interventional

Funder types

Industry

Identifiers

NCT00165854

2004-002597-33 (EudraCT Number)

E7070-E044-209

Details and patient eligibility

About

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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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