Study of E7070 Combined With Capecitabine to Determine Efficacy and Recommended Dose of Combination in Patients With Metastatic Colorectal Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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. []
Eligibility Criteria
Criteria
Part 1 Inclusion Criteria:
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Histologically or cytologically confirmed solid tumour refractory to standard therapy or for whom no established therapy exists
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Age >= 18 years
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Karnofsky performance status of >= 70%
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Life expectancy of >= 3 months
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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)
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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)
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Male and female patients
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Written informed consent to participate in the study
Part 1 Exclusion Criteria:
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More than two previous courses of documented myelosuppresive chemotherapy (epidermal growth factor targeted therapy does not constitute a course of chemotherapy)
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CNS metastases (a CT or MRI scan should be done if there is a clinical suspicion of CNS metastases)
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Major surgery, chemotherapy or radiation therapy (except palliative) within 4 weeks of treatment start
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Previous investigational cytotoxic treatment for malignant disease within 30 days before the start of the study
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Any treatment with non-oncological investigational drugs within 30 days before the start of the study
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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.
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Fertile males not willing to use contraception or whose female partners are not using adequate contraceptive protection
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Uncontrolled infections
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Clinically significant cardiac impairment or unstable ischaemic heart disease including a myocardial infarction within three months of study entry
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History of alcoholism, drug addiction, or any psychiatric or psychological condition which in the opinion of the investigator would impair study compliance
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History of hypersensitivity to sulphonamides
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Prior severe or unexpected reaction to fluoropyrimidine therapy (which may be explained by dihydropyrimidine dehydrogenase deficiency or hypersensitivity to 5-FU)
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Malabsorption syndrome or other condition which may affect absorption of drug
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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
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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:
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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.
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At least one unidimensionally measurable lesion according to the RECIST criteria
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Age ³ 18 years
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Karnofsky performance status of ³ 70%
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Life expectancy of ³ 3 months
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centre Léon Bérard | Lyon | France | F-69373 | |
| 2 | Institut Curie | Paris | France | F-75005 | |
| 3 | Universitätsklinikum der GHS-Essen | Essen | Germany | D-45122 | |
| 4 | Netherlands Cancer Institute | Amsterdam | Netherlands | 1066 CX |
Sponsors and Collaborators
- Eisai Limited
Investigators
- Study Director: Jantien Wanders, Eisai Limited
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- E7070-E044-209
- 2004-002597-33