Third line colorectal liver metastases
Conditions
Interventions
Product Name: Axitinib
Product Code: AG-013736
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
Imperial College Joint Research Office
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants must meet all of the following inclusion criteria to elgible for enrollment into the trial: • Histologically or cytologically confirmed adenocarcinoma of the colon or rectum with liver metastas(es). At least one of which should not have had any focal therapy including radiofrequency ablation, chemoembolization, ethanol or cryoablation. • Failed at least 2 chemotherapy regimens in advanced disease. • Evidence of unidimensionally measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). • 18 years of age or older. • ECOG performance status of 0 or 1. • Resolution of all acute toxic effects of prior therapy e.g. radiotherapy or surgical procedure to NCI CTCv4 grade =1. • Adequate organ function as defined by the following criteria: Serum aspartate aminotransferase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine aminotransferase (ALT; serum glutamic pyruvic transaminase [SGPT]) =2.5 x upper limit of normal (ULN). For patients with liver metastases, =65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Participants must be excluded if they present with any of the following exclusion criteria: • Non-exposed to both oxaliplatin and irinotecan FP based cytotoxic chemotherapy (prior pelvic radiation therapy including adjuvant or neoadjuvant chemo-radiation therapy for resected rectal cancer is allowed provided it is completed within 4 weeks prior to study entry) • Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John’s wort). • Any of the following within the 12 months prior to study drug administration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism. • Non-English speaking • Pregnancy, breastfeeding, or unwillingness/inability to employ an effective method of birth control/contraception to prevent pregnancy during treatment and for up to 3 months after discontinuing study drug if of reproductive potential. • Hypertension uncontrolled by medication (>150/100 mmHg despite optimal medical therapy). • Diagnosis of any second malignancy within the last 3 years that is potentially liable to interfere with study outcomes (basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma and hormone controlled locally advanced prostate cancer that has been adequately treated with no evidence of recurrent disease for 12 months, are allowed) • Prior surgery or IMP within 4 weeks prior to study entry • Current treatment within another therapeutic clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess whether an absence of vascular (blood-supply) shutdown in the tumour, in metastatic colorectal cancer, using contrast enhanced ultrasound, in patients taking Axitinib will quickly select out patients who are not going to obtain benefit from this drug. This group of non-responsive patients should have a similar overall survival as the placebo group, whereas the patients on Axitinib who do have vascular tumour shutdown on contrast enhanced ultrasound should obtain significant benefit.;Secondary Objective: The secondary objectives of this study are as follows: -To compare overall survival between Axitinib and 'dummy treatment' (placebo) -To compare disease progression free survival between Axitinib and placebo -To evaluate the use of 2 week contrast enhanced ultrasound assessing response when compared to an 8 week CT scan response criteria (RECIST)and see whether this correlates to the blood levels of Axitinib (PK levels) -To compare overall survival in patients who develop raised diastolic blood pressure (>90mmHg) on Axitinib compared to those who do not including the placebo group -To collect the side-effect profile for Axitinib and compare this to the placebo receiving patients;Primary end point(s): The primary outcome anticipated is that we expect a shorter median overall survival in participants exhibiting a =20% reduction from baseline in Contrast Enhanced Hepatic Perfusion Index (CEPHI) on Axitinib compared to those on Axitinib or placebo who have a >20% reduction in CEPHI. Overall survival is defined as the time from randomization to date of death due to any cause. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Median overall survival between the Axitinib and placebo arms (with an intention to treat analysis). • Comparison of disease progression in patients who fail to display reduction in CEHPI at 2 weeks (RECIST v1.1). • Best overall response rate (CR+PR) in Axitinib versus placebo groups. • Best overall response rate (CR+PR) in CEHPI responders versus non-responders. • Progression free survival and 6 and 9 month survival percentages and duration on study treatment between Axitinib and placebo. • Progression free survival and 6 and 9 month survival percentages and ‘duration on study treatment’ between CEHPI responders and non-responders.;Timepoint(s) of evaluation of this end point: 40 weeks from last randomisation. | — |
Countries
United Kingdom
Contacts
Public ContactBecky Ward
Imperial College Joint Research Office
Outcome results
None listed