Clear cell renal cell cancer with venous thrombus invasion Cancer Clear cell renal cell cancer with venous thrombus invasion
Conditions
Interventions
All participants will receive an 8 week course of Axitinib. Patients will be followed up every 2 weeks from day 1, week 1 of receiving Inlyta. All patients will start at 5mg BID with possible escalati
Sponsors
Common Services Agency
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 11/02/2019: 1. Aged 18 years and over 2. Biopsy-proven clear cell RCC 3. Immediate resection of the primary tumour considered technically possible 4. The patient must be suitable for and willing to undergo nephrectomy surgery 5. The clinical (radiologically determined) stage of the tumour must be into the main renal vein (cT3a, but seen in the main branch of the renal vein leading to but not beyond the vein ostium with the inferior vena cava (IVC)), or the IVC itself either below of above the diaphragm (cT3b or cT3c respectively) 6. Nodal status may be clinically node negative (cN0) on CT, indeterminate (cNx) or clinically node positive on CT (cN1) 7. Non-metastatic (M0) and metastatic (M1) clear cell renal cell patients 8. The patient must have an ECOG performance status of either 0 or 1 9. Urine must contain less than 2 g protein. If urine contains =2 g then a 24-h urine collection or urinary protein creatinine ratio (PCR) should be performed and the patient may enter NAXIVA only if urinary protein is <2g per 24 hours or PCR <200mg/mmol. 10. Serum Creatinine =1.5xULN or estimated Creatinine clearance =30mL/min as calculated using the Cockcroft- Gault (CG) equation. 11. All female patients with reproductive potential must have a negative serum or urine pregnancy test within a maximum of 14 days prior to starting trial treatment. Previous inclusion criteria as of 23/04/2018: 1. Aged 18 years and over 2. Biopsy-proven clear cell RCC 3. Immediate resection of the primary tumour considered technically possible 4. The patient must be suitable for and willing to undergo nephrectomy surgery 5. The clinical (radiologically determined) stage of the tumour must be into the main renal vein (cT3a, but seen in the main branch of the renal vein leading to but not beyond the vein ostium with the inferior vena cava (IVC)), or the IVC itself either below of above the diaphragm (cT3b or cT3c respectively) 6. Nodal status may be clinically node negative (cN0) on CT, indeterminate (cNx) or clinically node positive on CT (cN1) 7. Non-metastatic (M0) and metastatic (M1) clear cell renal cell patients 8. The patient must have an ECOG performance status of either 0 or 1 9. Urine must contain less than 2 g protein. If urine contains =2 g then a 24-h urine collection should be performed and the patient may enter if urinary protein is <2 g per 24 hours. 10. All female patients with reproductive potential must have a negative serum or urine pregnancy test within a maximum of 14 days prior to starting trial treatment. Previous inclusion criteria: 1. Aged 18 years and over 2. Biopsy proven clear cell RCC 3. Resectable Tumour 4. The clinical (radiologically determined) stage of the tumour must be into the main renal vein (cT3a, but seen in the main branch of the renal vein leading to but not beyond the vein ostium with the inferior vena cava (IVC)), or the IVC itself either below of above the diaphragm (cT3b or cT3c respectively) 5. Nodal status may be clinically node negative (cN0) on CT, indeterminate (cNx) or clinically node positive on CT (cN1) 6. Non-metastatic (M0) and Metastatic (M1) clear cell renal cell patients 7. Stratification by the Mayo classification
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 11/02/2019: 1. Metastatic patients with poor risk on the Memorial Sloan Kettering Cancer Centre (MSKCC) score and deemed suitable for cytoreductive nephrectomy at time of enrolment 2. Other invasive malignancy within the last 2 years. Patients with previous history of malignancies with a negligible risk of metastasis or death and treated with expected curative intent are eligible, for example but not exclusively: 2.1. Carcinoma in situ of the cervix. 2.2 Basal or squamous cell skin cancer. 2.3 Localized low to intermediate risk prostate cancer treated with curative intent and absence of prostate specific antigen (PSA) relapse; or prostate cancer (Stage T1/T2a, Gleason =6 and PSA 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. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy. 4. Current signs or symptoms of severe progressive or uncontrolled hepatic, endocrine, pulmonary disease other than directly related to RCC 5. Gastrointestinal abnormalities including: 5.1. Inability to take oral medication 5.2. Requirement for intravenous alimentation 5.3. Prior surgical procedures affecting absorption including total gastric resection 5.4. Treatment for active peptic ulcer disease in the past 6 months 5.5. 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 5.6. Malabsorption syndromes 6. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (see section 8.12, concomitant therapy) 7. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (see section 8.12, concomitant therapy) 8. 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. 9. Active seizure disorder, spinal cord compression, or carcinomatous meningitis 10. Any of the following within 12 months prior to study entry: 10.1 myocardial infarction 10.2 uncontrolled angina 10.3 coronary/peripheral artery bypass graft 10.4 symptomatic congestive heart failure 10.5 cerebrovascular accident or transient ischemic attack 11. Uncontrolled hypertension (>160/100 mmHg despite optimised antihypertensive treatment) 12. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness 13. ALT or AST =1.5 x upper limit of normal; Bilirubin =1.5 x upper limit of normal 14. Serum creatinine =1.5 x upper limit of normal 15. Neutrophil count <1.0 x 10(9)/l; platelet count <100 x 10(9)/l; Hb =90 g/l 16. Known severe hepatic impairment (Child-Pugh class C) 17. Known hypersensitivity to axitinib or any of its excipients. Specifically patients with hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not enter the study. Previous exclusion criteria as of 23/04/2018: 1. Metastatic patients with poor risk on the Memorial Sloan Kettering Cancer Ce
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Thrombus invasion will be measured using MRI scanning according to the Mayo classification at baseline and pre-surgery (week 9). | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 23/04/2018: 1. Percentage change in surgical approach (to a less invasive surgical approach) as assessed by review of MRI scans by surgeons at baseline and week 9 (i.e after axitinib therapy has been completed) 2. Percentage change in height of the cancer invasion into the large blood vessels draining the kidney (venous tumour thrombus). This will be evaluated by comparing baseline and week 9 scans. Local radiologists will conduct the evaluation and a central radiology review will be conducted. 3. Objective tumour response rate measured by MRI/CT scans at baseline and week 9. 4. Complications of surgery (i.e. blood loss and need for a blood transfusion) assessed according to the Clavien-Dindo classification of surgical complications at baseline and week 9 Previous secondary outcome measures 1. Percentage change in surgical approach is assessed by review of MRI scans by surgeons at baseline and 9 weeks 2. Percentage change in height of the venous tumour thrombus will be evaluated by comparing baseline and week 9 scans. Local Radiologists will conduct the evaluation and a central radiology review will be conducted. 3. The response rate (RECIST) will be measured by MRI/CT at baseline and week 9 4. Change in Inferior vena cava- tumour thrombus volume will be assessed by radiologists comparing CT/MRI scans taken at baseline and week 9 5. Morbidity will be measured using MRI/CT scanning according to the Clavien-Dindo classification at baseline and week 9 | — |
Countries
England, Scotland, United Kingdom
Contacts
Public ContactKathleen Riddle
Outcome results
None listed