Colorectal Cancer
Conditions
Keywords
Colorectal, Metastatic, Chemorefractory, Ultrasound, Aflibercept
Brief summary
Various antiangiogenic agents have a modest effect in prolonging overall survival in solid tumours. In colorectal cancer it is clear that there are some patients in whom bevacizumab significantly prolongs survival, but it is not effective in the majority of patients. Biomarker studies using tumour tissue and blood have failed to define a consistent biomarker that correlates with a beneficial effect of bevacizumab on survival. DCE-MRI can detect changes in tumour blood flow which, in early phase drug studies, correlated with subsequent tumour responses, but is too expensive and time consuming to be used in larger scale trials. DCE-US is a promising biomarker for use in this group of patients with antiangiogenic agents, as detailed above. The investigators wish to use this technique as a predictive biomarker for any effects Aflibercept has on OS and PFS in patients with metastatic colorectal cancer refractory to standard treatment.
Interventions
DRUGAflibercept
Antiangiogenic
PROCEDUREDynamic Contrast Enhanced Ultrasound
DCE-US (a technique using differential liver blood flow assessments using microbubble) will be performed at baseline, Week 2 and 8 of treatment.
Sponsors
Sanofi
Barts & The London NHS Trust
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
No masking
Intervention model description
Single arm study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1\. Histologically or cytologically confirmed adenocarcinoma of the colon or rectum with liver metastasis(es), at least one of which should not have had any focal therapy including radiofrequency ablation. 2\. Evidence of uni-dimensionally measurable disease as defined by the Response Evaluation Criteria in Solid Tumours (RECIST). 3\. 18 years of age or older. 4\. ECOG performance status of \< 3. 5\. Failed (or intolerant of) at least 2 chemotherapy regimens in advanced disease and resolution of any acute toxic effects of prior therapy e.g. radiotherapy or surgical procedure to NCI CTCv4 grade ≤1. No other alternative available effective treatment options. 6\. Adequate organ function as defined by the following criteria: * Serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) ≤5 x upper limit of normal (ULN). * Total serum bilirubin \<1.5 x ULN * Serum albumin ≥25mg/dl * Absolute neutrophil count ≥1000/µL * Platelets ≥75, 000/µL * Haemoglobin ≥9.0 g/dL * Serum creatinine ≤1.5 x ULN 7\. Willingness and ability to provide fully informed consent to participate in the study. 8\. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. 9\. Willingness to maintain good oral hygiene and receive regular dental assessments. No evidence of oral infection or planned dental surgery (excluding fillings). 10\. Willingness to donate archival diagnostic tissue for translational research.
Exclusion criteria
1. Palliative radiotherapy to non-target, metastatic lesions will be allowed. 2. Less than 4 weeks following major surgery to the time of inclusion or until the surgical wound is fully healed, whichever came later (48 hours in case of minor surgical procedure or until wound full healing observed). 3. Less than 4 weeks elapsed from prior radiotherapy or prior chemotherapy to the time of inclusion. 4. Treatment with any investigational drug within 30 days prior to inclusion. 5. Adverse events (with exception of alopecia, peripheral sensory neuropathy and those listed in specific
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival | 1 year |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free survival | 1 year |
Outcome results
None listed