A Randomised, Double-blind, Multicentre Phase II/III Study to Compare the Efficacy of AZD2171 in Combination with 5-fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX), to the Efficacy of Bevacizumab in Combination with FOLFOX in Patients with Previously Untreated Metastatic Colorectal Cancer

• Conditions: This is a Phase II / III trial in Patients with Previously Untreated Metastatic Colorectal Cancer.; MedDRA version: 8.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancer

• Registration Number: EUCTR2005-003440-66-CZ
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-08-08
• Last Update Posted: 12 May 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1600

Inclusion Criteria

For inclusion in the study, patients must fulfil all of the following criteria:

Provision of written informed consent.
Males or females aged 18 years and older.
Histological or cytological confirmation of carcinoma 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 criteria). Patients who have previously been disease free following a neoadjuvant chemotherapy regimen and resection of all primary tumours and metastatic disease are eligible provided they have measurable disease as above
Patients must have received no prior systemic therapy for metastatic disease. Any adjuvant/neo-adjuvant oxaliplatin therapy must have been received more than 6 months prior to study entry
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

Any of the following is regarded as a criterion for exclusion from the study:

Termination of adjuvant oxaliplatin therapy within 12 months of study entry or termination of adjuvant 5FU therapy within 6 months of study entry.
Any unresolved toxicity >CTC grade 1 from previous anticancer therapy (including radiotherapy) except haematological toxicity and alopecia.
Prior therapy with monoclonal antibodies or small molecule inhibitors against VEGF or VEGF receptors, including bevacizumab and cedaranib.
Prior therapy with oxaliplatin within 12 months of study entry.
Untreated brain or meningeal metastases. Patients with radiological evidence of stable brain metastases are eligible providing they are asymptomatic and either do not require corticosteroids or have been treated with corticosteroids with clinical and radiological evidence of stabilisation at least 10 days after discontinuation of steroids
Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count less than or equal to 1.5 x 10 to the power 9/L or platelet count less than or equal to 100 x 10 to the power 9/L or requiring regular blood transfusions to maintain haemoglobin >9 g/dL.
Serum bilirubin greater than or equal to 1.5 x upper limit of reference range (ULRR) except in the case of Gilberts syndrome.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to 2.5 x ULRR. If liver metastases are present, ALT or AST >5 x ULRR.
Serum creatinine >1.5 x ULRR or a creatinine clearance of less than or equal to 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 unless urinary protein, <1.5 g in a 24 hour urine collection.
Patients with a history of poorly controlled hypertension or 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 5mmHg, then an additional reading should be obtained, and averaged.
Any evidence of severe or uncontrolled systemic diseases (eg, unstable or uncompensated respiratory, cardiac including arrhythmias, hepatic or renal disease).
Mean QTc with Bazett’s correction >470 msec in screening ECG or history of familial long QT syndrome (as per ICH guideline E14).
Recent (<28days) major abdominal or thoracic surgery prior to entry into the study, or a procedure considered to have a significant risk of internal bleeding. Presence of a surgical wound incision that is not fully healed.
Significant haemorrhage (>30mL/bleeding episode in previous 3 months) or haemoptysis (>5mL fresh blood) in previous 4weeks) or thrombotic event (including transient ischaemic attack) in the previous 12 months.
Pregnant or breast-feeding women or women of childbearing potential with a positive pregnancy test prior to receiving study medication.
Known severe hypersensitivity to cedaranib, bevacizumab, oxaliplatin, 5 FU, or leucovorin, or any of the excipients of these products.
Other concomitant anti-cancer therapy.
History of other malignancies (except for adequately treatedbasal or squamous cell carcinoma in situ) within 5 years unless the patient has been disease free for 2 years and there is a tissue diagnosis of the primary cancer of interest from a tar

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified