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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00165854
• Date of registration: 13/09/2005
• Prospective Registration: No
• Primary sponsor: Eisai Limited
• Public title: Study of E7070 Combined With Capecitabine to Determine Efficacy and Recommended Dose of Combination in Patients With Metastatic Colorectal Cancer
• Date of first enrolment: March 2003
• Target sample size: 46
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00165854
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

France, Germany, Netherlands

Contacts

• Name: Jantien Wanders
• Affiliation: Eisai Limited

Key inclusion & 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



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Colorectal Cancer (CRC)

Intervention(s)

Drug: E7070

Primary Outcome(s)

to determine the safety, tolerability and efficacy (in terms of response rate and progression-free survival) of the combination in patients with metastatic CRC.

To determine the recommended dose of E7070 in combination with capecitabine by dose adjustment;

Secondary Outcome(s)

measure duration of response and stable disease; to measure median and one year survival.

Determine the pharmacokinetic profile of capecitabine and E7070 when administered in combination;

Secondary ID(s)

E7070-E044-209

2004-002597-33

Source(s) of Monetary Support

Please refer to primary and secondary sponsors