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

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eisai Limited
• Treatments: N-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide

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