Metastatic colorectal cancer
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Provision of written informed consent. - Males or females aged 18 years and older. - Histological or cytological confirmation of adenocarcinoma of the colon or rectum. - Stage IV (metastatic) disease with one or more measurable lesions at least 10 mm in the longest diameter by spiral computed tomography scan or 20 mm with conventional techniques (RECIST). - Patients must have received one prior systemic therapy for metastatic disease. - Patients must have documented progression during or following first line therapy. - Patients must be suitable for subsequent treatment with FOLFOX. - World Health Organisation (WHO) Performance score =2. - Life expectancy of =12 weeks. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Any unresolved toxicity >CTC grade 2 from previous treatments. - Prior therapy with FOLFOX or other oxaliplatin containing regimens including adjuvant therapy 9 g/dl. - Serum bilirubin ³1.5 x upper limit of reference range (ULRR). - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ³2.5 x ULRR. If liver metastases are present, ALT or AST >5 x ULRR. - Serum creatinine >1.5 x ULRR or a creatinine clearance of £50 mL/min calculated by Cockroft-Gault formula (see Section 4.7.2.2). - Greater than +1 proteinuria on 2 consecutive dipsticks taken no less than 1 week apart or if urinary protein =1.5 g in a 24 hour urine collection. - Patients with a history of poorly controlled hypertension with resting BP >150/100 mmHg in the presence or absence of a stable regimen of anti hypertensive therapy. Measurements will be made after the patient has been resting supine for a minimum of 5 minutes. Two or more readings should be taken at 2 minute intervals and averaged. If the first 2 diastolic readings differ by more than 5 mmHg then an additional reading should be obtained, and averaged. - Any evidence of severe or uncontrolled systemic diseases (eg, unstable or uncompensated respiratory disease, cardiac disease including arrhythmias, hepatic or renal disease). - Mean QTc with Bazett’s correction >470 msec in screening electrocardiogram (ECG) or history of familial long QT syndrome (as per ICH guideline E14). - Recent (30 mL/episode in previous 3 months) or haemoptysis (>5 mL fresh blood in previous 4 weeks). - Pregnant or breast-feeding women or women of childbearing potential with a positive pregnancy test prior to receiving study medication. - Known severe hypersensitivity to AZD2171, bevacizumab, oxaliplatin, 5 FU or leucovorin, or any of the excipients of these products. - Other concomitant anti-cancer therapy. - History of other malignancies within 5 years except for adequately treated basal or squamous cell skin cancer or carcinoma in situ. - History of central nervous disorders or uncontrolled seizures. - History of significant gastrointestinal impairment, as judged by the investigator that would significantly affect the absorption of AZD2171. - Peripheral neuropathy. - Known dihydropyrimidine dehydrogenase deficiency. - Hypersensitivity to Chinese hamster ovary cell products or other recombinant or humanised antibo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the efficacy of AZD2171 in combination with FOLFOX compared to efficacy of bevacizumab in combination with FOLFOX by assessment of PFS; Secondary Objective: - The efficacy of AZD2171 in combination with FOLFOX compared to the efficacy of bevacizumab in combination with FOLFOX by assessment of overall survival (OS) and overall response rate (ORR; complete response [CR] + partial response [PR]). - The effects on quality of life (QoL) and disease-related symptoms, as assessed by FACT C, of AZD2171 in combination with FOLFOX, compared with the effects of bevacizumab in combination with FOLFOX. - The safety and tolerability of randomised study therapies in combination with FOLFOX. ; Primary end point(s): The primary variable for the study is PFS. All patients will be followed until evidence of one of the following: - progression of disease (patients will be followed for subsequent therapy and death) - death without evidence of progression | — |
Countries
Austria, Belgium, Czech Republic, Germany, Slovakia, Spain, United Kingdom
Outcome results
None listed