A Phase II Study of Axitinib in Patients With Metastatic Renal Cell Cancer Unsuitable for Nephrectomy (A-PREDICT)
A-PREDICT is a study of axitinib in patients with metastatic renal cell carcinoma unsuitable for nephrectomy (as judged by the treating clinician) to evaluate efficacy, safety, toxicity and changes in biomarkers during therapy. Axitinib will given twice daily by mouth according to tolerability of treatment, for as long as patients are deriving clinical benefit. Blood and tumour tissue samples will be taken prior to and during therapy to evaluate biomarkers of treatment response. The primary clinical objective of this study is to define the activity of axitinib given to patients with metastatic renal cell carcinoma unsuitable for nephrectomy.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A-PREDICT: A Phase II Study Of Axitinib In Metastatic Renal Cell Cancer in Patients Unsuitable for Nephrectomy|
- Freedom from progression at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]The proportion of study participants alive and progression free at 6 months (day 1 week 25 visit). Progression will be measured from the date of study entry (registration date) until the first date of either death or confirmed progressive disease according to RECIST. Patients alive and free from progression will be censored at the date of last follow-up. The proportion of patients progression free at 6 months will be reported with 95% confidence interval. In addition, progression free survival will be presented using the Kaplan Meier product limit method with median progression free survival reported. A blinded central review of CT scans will be conducted for verification purposes.
- Best overall response [ Time Frame: During treatment +30 days ] [ Designated as safety issue: No ]Best tumour response that is achieved during or within 30 days after termination of axitinib that is confirmed according to RECIST
- Progression free survival [ Time Frame: Study duration (assessed week 9, 17, 25, and 4 weekly until progression) ] [ Designated as safety issue: No ]Progression-free survival (PFS) will be measured from the date of registration until first date of either death or confirmed progressive disease according to RECIST 1.1. Time to last follow-up will be used if patient has not progressed or died and PFS time for the patient will be considered censored. A Kaplan Meier graph and median survival time will be presented.
- Overall survival [ Time Frame: Study duration (estimated median overall survival (OS) of 10.9 months) ] [ Designated as safety issue: No ]Overall survival will be measured from the date of registration until the date of death due to any cause. Time to last follow-up will be used if patient has not died and survival time for the patient will be considered censored.
- Safety and toxicity of axitinib (by NCI CTC grading version 4) [ Time Frame: Treatment duration (at least 4 weekly, and again at disease progression - likely to be 6 months) ] [ Designated as safety issue: Yes ]
- Number of patients who become suitable for nephrectomy as a consequence of therapy with axitinib [ Time Frame: Study duration (assessed by clinician over treatment duration which is estimated at 6 months) ] [ Designated as safety issue: No ]The proportion of patients who undergo nephrectomy following registration as a result of treatment with axitinib will be reported with 95% confidence intervals.
- EXPLORATORY ENDPOINT: Molecular and pathological changes in biomarkers as a consequence of axitinib therapy [ Time Frame: Treatment duration (Baseline, Day 1 week 8, and again at disease progression) ] [ Designated as safety issue: No ]
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||September 2016|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Axitinib - oral tablet twice daily until disease progression. Starting dose 5mg.
Axitinib treatment Axitinib is an oral VEGF-receptor inhibitor. Patients are prescribed a starting dose of 5mg twice daily, escalating to 10mg in absence of dose limiting toxicities.
Patients should stop axitinib treatment one week prior to day 1 week 9 percutaneous research biopsy of the primary renal tumour and restart 2-3 days post biopsy.
Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day.
Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol.
Other Name: AG-013736
A-PREDICT is a single arm, single agent, open label, multicentre, phase II study of axitinib in patients with metastatic renal cell carcinoma of predominant clear cell histology and unsuitable for debulking nephrectomy (as judged by the treating clinician). Patients who have provided consent and have satisfied the eligibility criteria will be registered into the trial.
The starting dose of axitinib will be 5 mg twice daily by mouth, escalating to a maximum of 10mg twice daily by mouth according to tolerability of treatment, for as long as patients are deriving clinical benefit. Treatment will be paused for one week prior to percutaneous biopsy of the primary on day 1 week 9. Disease progression will be evaluated according to RECIST v1.1 criteria 8 weeks after commencing treatment, at 8 weekly intervals to 6 months and 3 monthly thereafter. Blood and tumour tissue samples will be taken prior to and during therapy to evaluate biomarkers of treatment response. Nephrectomy will be carried out on any patient who becomes suitable in the opinion of the treating clinician during the course of the trial. Where possible, tissue samples will be taken from resected specimens. Response to axitinib in marker lesions will be correlated with changes in biomarkers.
|Contact: A-PREDICT Trial Manager||0208 722 email@example.com|
|Royal Marsden Hospital - sutton||Recruiting|
|London, Sutton, United Kingdom, SM2 5PT|
|Principal Investigator: James Larkin, Dr|
|Cambridge, United Kingdom, CB2 0QQ|
|Principal Investigator: Timothy Eisen, Prof|
|Royal Marsden Hospital||Recruiting|
|London, United Kingdom, SW3 6JJ|
|Principal Investigator: James Larkin, Dr|
|Manchester, United Kingdom, M20 4BX|
|Principal Investigator: Robert Hawkins, Prof|
|Plymouth, United Kingdom, PL6 8DH|
|Principal Investigator: Martin Highley, Dr|
|Royal Surrey County Hospital||Recruiting|
|Surrey, United Kingdom, GU2 7XX|
|Principal Investigator: Agnieszka Michael, Dr|
|Principal Investigator:||James Larkin||Royal Marsden Hospital, London|