Metastatic colorectal cancer MedDRA version: 8.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer
Conditions
Interventions
Product Name: RECENTIN
Product Code: AZD2171
Pharmaceutical Form: Film-coated tablet
CAS Number: 288383-20-0
Current Sponsor code: AZD2171
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in the study patients must fulfill all of the following criteria: Provision of written informed consent Male or female aged 18 years or over Histological or cytological confirmation of carcinoma of the colon or rectum Patients requiring chemotherapy for 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 must have received no prior systemic therapy for metastatic disease. Any adjuvant/neoadjuvant oxaliplatin therapy must have been received greater than 12 months prior to study entry and neoadjuvant 5FU must have been received greater than 6 months prior to study entry. Patients whio have previously been disease free following a neoadjuvant chemotherapy regimen and resection of all primary tumour and metastatic disease are eligible. WHO Performance score of 0 or 1 Life expectancy of greater than or equal to 12 weeks For inclusion in the optional genetic research and biomarker analysis components of the study (blood and archival tumour sampling for DNA extraction and retrospective pharmacogenetic analysis and tumour biomarker analysis), patients must fulfill the following criteria: Provision of written informed consent for blood sampling for genetic research and/or Provision of written informed consent for tumour sampling for genetic research and biomarker analysis If a patient declines to participate in either of these components of the study, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this Clinical Study Protocol, as long as they have consented to the main study. 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 of the following is regarded as a criterion for exclusion from the study: Adjuvant/neoadjuvant oxaliplatin therapy within 12 months of study entry or adjuvant/neoadjuvant 5FU therapy within 6 months of study entry Any unresolved toxicity greater than CTC grade 1 from previous anti-cancer 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 AZD2171 Untreated unstable brain or meningeal metastases. Patients with radiological evidence of stable brain metastases are eligible providing that 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 greater than 9 g/dL Serum bilirubin greater than or equal to 1.5 x upper limit of reference range (ULRR) except in the case of known 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 greater than 5 x ULRR Serum creatinine greater than 1.5 x ULRR or a creatinine clearance of less than or equal to 50 mL/min calculated by the Cockcroft-Gault formula Greater than +1 proteinuria on 2 consecutive dipsticks taken no less than 1 week apart unless urinary protein less than 1.5 g in a 24 hour period A history of poorly controlled hypertension or resting BP greater than 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 two 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, cardiac, hepatic or renal disease) Known risk to the patient of transmitting `HIV or hepatitis B or C via infected blood Mean QTc with Bazett’s correction greater than 470 msec in screening ECG or history of familial long QT syndrome (as per ICH guideline E14) Recent (less than 28 days) major thoracic or abdominal surgery prior to entry into the study or a surgical incision that is not fully healed Significant haemorrhage (greater than 30 ml/bleeding episode in previous 3 months), haemoptysis (greater than 5 ml fresh blood in previous 4 weeks) or thrombotic event (including transient ischaemic attack) in the previous 12 months Pregnant or breast feeding women or women of child bearing potential with a positive pregnancy test prior to receiving study treatment Known hypersensitivity to AZD2171, oxaliplatin, 5-FU, leucovorin, capecitabine or any of the excipients of these products Other concomitant anti-cancer therapy (including LHRH agonists), except steroids History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years, unless the patient has been disease free for that other malignancy for 2 years and there is a tissue diagnosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Overall survival and Progression Free Survival will be co-primary endpoints;Secondary Objective: The efficacy of cedaranib when added to FOLFOX or XELOX compared to the efficacy of FOLFOX or XELOX alone in patients with previously untreated metastatic CRC by assessment of overall response rate (ORR: complete response (CR) plus PR) and duration of response. The rate of resection of liver metastases in patients with previously untreated metastatic CRC receiving cedaranib when added to FOLFOX or XELOX compared to patients receiving FOLFOX or XELOX alone. The incidence of wound healing complications in patients with previously untreated metastatic CRC receiving cedaranib when added to FOLFOX or XELOX compared to patients receiving FOLFOX or XELOX alone. The safety and tolerability of AZD2171 when added to FOLFOX or XELOX compared to the safety and tolerability of FOLFOX or XELOX alone.;Primary end point(s): Overall survival ond Progression Free Survival are co-primary endpoints | — |
Countries
Czech Republic, Germany, Hungary, United Kingdom
Outcome results
None listed