Metastatic renal cell carcinoma MedDRA version: 19.0 Level: LLT Classification code 10050076 Term: Metastatic renal carcinoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Axitinib
Product Code: AG-013736
Pharmaceutical Form: Tablet
INN or Proposed INN: Axitinib
CAS Number: 319460-85-0
Concentration unit: mg milligram(s)
Concentration type: equal
Concentra
Sponsors
Institute of Cancer Research
The Royal Marsden Hospital NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
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 (see Appendix A) 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 =65 years) yes F.1.3.1 Number of subjects for this age range 19
Exclusion criteria
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 post-surgery. 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: a. inability to take oral medication; b. requirement for intravenous alimentation; c. prior surgical procedures affecting absorption including total gastric resection; d. treatment for active peptic ulcer disease in the past 6 months; e. 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; f. malabsorption syndromes. 7. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (see section 8.12, concomitant therapy). 8. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (see section 8.12, concomitant therapy). 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. 14. Known galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Does treatment with axitinib stop previously untreated widespread kidney cancer that can't be surgically removed from getting worse for at least 6 months?;Secondary Objective: SECONDARY RESEARCH QUESTIONS: What is the largest reduction in a participant's cancer seen during treatment with axitinib? How long does treatment with axitinib stop participants' cancer from getting worse? How long does treatment with axitinib keep people alive? What are the side effects of treatment with axitinib in this group of patients? How many participants' will be able to have surgery to remove their kidney due to treatment with axitinib? EXPLORATORY QUESTION: Are there biological or genetic markers that could be used to indicate who will respond best to axitinib treatment in future?;Primary end point(s): The proportion of patients treated with axitinib who are free from disease progression 6 months from the commencement of treatment. 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 Response Evaluation Criteria In Solid Tumors (RECIST)v1.1. The main timepoint of interest is 6 months after study entry.;Timepoint(s) of evaluation of this end point: 6 months from start of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Best overall response confirmed according to RECIST v1.1. • Progression free survival confirmed according to RECIST v1.1. • Overall survival • Safety and toxicity of axitinib (by NCI CTC grading version 4). • Number of patients who become suitable for nephrectomy as a consequence of therapy with axitinib. All secondary endpoints will be measured from time of registration. ;Timepoint(s) of evaluation of this end point: Best overall response - during or within 30 days after termination of axitinib Progression-free survival - first date of either death or confirmed progressive disease - 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. Overall survival will be measured 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 will be assessed throughout the treatment period. Number of patients suitable for nephrectomy will be assessed at time of last follow up. | — |
Countries
United Kingdom
Contacts
Public ContactRachel Todd
The Institute of Cancer Research
Outcome results
None listed