Metastatic or locally recurrent colorectal cancer in genetically unselected patients, followed by recruitment of patients selected for microsatellite positive tumours MedDRA version: 9.1 Level: LLT Classification code 10010035 Term: Colorectal cancer stage IV MedDRA version: 9.1 Level: LLT Classification code 10010030 Term: Colorectal cancer recurrent
Conditions
Interventions
Product Name: patupilone
Product Code: EPO906A
Pharmaceutical Form: Intravenous infusion
INN or Proposed INN: patupilone
CAS Number: 152044-54-7
Current Sponsor code: EPO906A
Other descriptive name: e
Sponsors
Royal Marsden Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically confirmed metastatic or locally recurrent carcinoma of the colon or rectum • Prior therapy with oxaliplatin, 5-fluoropyrimidine and irinotecan • Availability of paraffin embedded tumour tissue for analysis of MSI status and CIN • Male or female • 18 years of age or older • Life expectancy of 12 weeks or greater • ECOG performance status 0 or 1 • Clinically and/or radiographically documented measurable disease • Adequate liver function: i. Serum aspartate transaminase (AST) = 5 x upper limit of normal (ULN) ii. Serum alanine transaminase (ALT) = 5 x ULN iii. Serum alkaline phosphatase (ALP) 50ml/min • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures • Prior radiotherapy or colostomy are allowed • Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects prior to enrolment • For Cohort B, all patients must have tumours which are MSI positive by IHC 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: • Persistent toxicity from previous treatment. Neurotoxicity from prior oxaliplatin must have resolved to at least grade 1. • Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell carcinoma of the skin, or adequately treated in-situ cervical cancer • Any of the following within the 12 months prior to study drug administration i. Myocardial infarction or severe/unstable angina, ii. Coronary/peripheral artery bypass graft iii. Symptomatic congestive heart failure iv. Cerebrovascular accident or transient ischemic attack v. Pulmonary embolism • Pregnancy or breastfeeding • Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the anti-tumour activity of EPO906 administered to patients with metastatic or localy recurrent colorectal cancer;Primary end point(s): 12 weeks progression free survival in unselected patients;Secondary Objective: i. To determine the effect of CIN and MSI on the efficacy of EPO906 as an anticancer agent ii. To describe the safety of EPO906 and quality of life benefits associated with treatment iii. To correlate specific genetic variation with outcome following EPO906 therapy, in particular with reference to APC status (MSI+ APCwt vs MSI APCmutant vs CIN). Other genetic analysis will include but not be limited to, b-catenin, Kras, or Braf mutations; copy number polymorphisms; LOH iv. To retrospectively assess the response to prior treatment in relation to MSI and CIN status, particularly with reference to response to Irinotecan and Oxaliplatin containing regimens Exploratory objectives To correlate radiological abnormalities at initial presentation with subsequent histopathology, CIN/MSI status, response to treatment, development of metastases, pattern of disease, survival | — |
Countries
United Kingdom
Outcome results
None listed