Plain English Summary
Ms Rachel Todd
Institute of Cancer Research Clinical Trials & Statistics Unit (ICR-CTSU)
Section of Clinical Trials
Sir Richard Doll Building
15 Cotswold Road
A Phase II study of axitinib in patients with metastatic renal cell cancer unsuitable for nephrectomy
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 the week 9 biopsy. 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.
First MREC, 08/05/2012 ref: 12/LO/0639
Non-randomised interventional trial
Primary study design
Secondary study design
Non randomised study
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Oral axitinib twice a day. 5mg starting dose escalated to maximum of 10mg until disease progression
Primary outcome measure
Freedom from progression at 6 months, measured at 6 months after start of treatment
Secondary outcome measures
No secondary outcome measures
Overall trial start date
Overall trial end date
Reason abandoned (if study stopped)
Participant inclusion criteria
1. Histologically confirmed metastatic renal cell carcinoma of predominant clear cell histology
2. Unsuitable for nephrectomy as judged by treating clinician(s)
3. Not suitable for watch and wait policy as determined by treating clinician(s)
4. No prior systemic therapy for renal cell carcinoma
5. Measurable metastatic disease using RECIST v1.1
6. 18 years of age or older
7. Life expectancy of 12 weeks or greater
8. ECOG performance status 0 or 1
9. Adequate organ function as defined by serum aspartate transaminase (AST) and serum alanine transaminase (ALT) =2.5 x upper limit of normal (ULN), or AST and ALT =5 x ULN if liver function abnormalities are due to liver metastases; total serum bilirubin =1.5 x ULN
10. Adequate haematological function as defined by absolute neutrophil count (ANC) =1500/µL, platelets =75,000/µL, haemoglobin =9.0 g/dL and prothrombin time (PT) =1.5 x ULN
11. Serum creatinine =1.5 x ULN or calculated creatinine clearance = 60 mL/min;
12. Urinary protein <2+ by urine dipstick. If dipstick is =2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is <2g per 24 hours.
13. No evidence of pre-existing uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be =140 mm Hg, and the baseline diastolic blood pressure readings must be =90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
14. Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment.
15. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including tumour biopsies.
16. Written informed consent
17 Male or female participants
Target number of participants
UK Sample Size: 99
Participant exclusion criteria
1. The presence of intracranial disease, unless there has been radiological evidence of stable intracranial disease >6 months. In the case of a solitary brain metastasis which has been resected, there must be evidence of a disease-free interval of at least 3 months postsurgery. All patients previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days.
2. The presence of active second malignancy. Patients will be eligible if they have adequately treated basal cell carcinoma, squamous cell skin cancer, in situ cervical cancer, stable prostate cancer or if treated with curative intent for any other cancer with no evidence of disease for 2 years.
3. Women who are pregnant or are breastfeeding. Female patients must be surgically sterile, be postmenopausal, or must agree to use effective contraception during the period of therapy. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrolment.
4. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy.
5. Current signs or symptoms of severe progressive or uncontrolled hepatic, endocrine, pulmonary disease other than directly related to RCC.
6. Gastrointestinal abnormalities including:
6.1. Inability to take oral medication
6.2. Requirement for intravenous alimentation
6.3. Prior surgical procedures affecting absorption including total gastric resection
6.4. Treatment for active peptic ulcer disease in the past 6 months
6.5. Active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy;
6.6. Malabsorption syndromes.
7. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors
8. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers
9. Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose anticoagulants for maintenance of patency of central venous access device or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed.
10. Active seizure disorder, spinal cord compression, or carcinomatous meningitis.
11. Any of the following within 12 months prior to study entry: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack.
12. Deep vein thrombosis or pulmonary embolism within 6 months prior to study entry.
13. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Institute of Cancer Researc Clinical Trials & Statistics Unit (ICR-CTSU)
Institute of Cancer Research (UK)
Experimental Cancer Medicine Centre
123 Old Brompton Road
Funding Body Type
private sector organisation
Funding Body Subtype
Results and Publications
Publication and dissemination plan
To be confirmed at a later date
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)