Study of Axitinib for Reducing Extent of Venous Tumour Thrombus in Renal Cancer With Venous Invasion
Condition: Renal Cell Carcinoma; Metastatic Renal Cell Carcinoma; Non-metastatic Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell; Thrombosis
Intervention: Axitinib Oral Tablet
Intervention description: 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 and blood pressure.
Doses should be taken approximately 12 hours apart and patients should be instructed to take their doses at approximately the same times each day with or without food as per instruction. On clinic days only, patients will be advised to fast for 6 hours prior to their clinic visit.
Patients should be advised to stop axitinib treatment a minimum of 36 hours and maximum of 7 days prior to week 9 nephrectomy and thrombectomy surgery.
Dose adjustments, including dose increase or dose reduction, are permitted and should be based on clinical judgement and the guidelines provided in the protocol.
Intervention MeSH terms: Axitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Neoadjuvant; Venous Tumour Thrombus; Axitinib; Mayo Classification; Nephrectomy; Thrombectomy

Summary:

      NAXIVA is a study of axitinib in patients with metastatic and non-metastatic renal cell
      carcinoma with venous invasion. Patients will be given axitinib (twice daily) for 8 weeks (at
      an escalated dose) and the response of the venous invasion will be assessed.

      Blood, urine and tumour tissue samples will be taken prior to and during therapy to evaluate
      biomarkers of treatment response.

      The primary objective is to assess the response of the thrombus to axitinib. Its thought that
      axitinib will reduce the extent of the thrombus in the inferior vena cava will reduce the
      extent of surgical intervention.
    

Eligibility criteria:

        Inclusion Criteria:

        1. Age ≥ 18. 2. Histologically proven clear cell RCC. 3. Immediate resection of the primary
        tumour considered technically possible. 4. Suitable for and willing to undergo nephrectomy
        (either cytoreductive or with curative intent) 4. cT3b, cT3c, cT3a (main renal vein) 5. N0,
        N1, or Nx 6. M0, or M1 7. ECOG performance status 0 - 1 8. Urinalysis <2+ protein. If
        dipstick is ≥2+ then a 24-hour urine collection should be performed and the patient may
        enter NAXIVA only if urinary protein is <2g per 24 hours.

        9. 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.

        Exclusion Criteria:

          1. For M1 patients: poor risk on Memorial Sloan Kettering Cancer Centre (MSKCC) score and
             deemed suitable for cytoreductive nephrectomy at time of enrolment.

          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. Patients with prostate cancer will be
             permitted entry if not receiving treatment and prostrate-specific antigen (PSA) is not
             rising.

          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 and up to 1 week after treatment.

             Male patients must be surgically sterile or must agree to use effective contraception
             during the period of therapy and for 6 months after completion of study drug (Patients
             who do not meet this will not be are not eligible).

          4. Current signs or symptoms of severe progressive or uncontrolled hepatic, endocrine or
             pulmonary disease other than directly related to RCC.

          5. 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.

          6. Current use or anticipated need for treatment with drugs that are known potent CYP3A4
             inhibitors (see section 4.4, concomitant therapy).

          7. Current use, or anticipated need for treatment with, drugs that are known CYP3A4
             inducers or substrates for CYP1A2 (see section 4.4, 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: myocardial infarction,
             uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive
             heart failure, 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 ULN; Bilirubin ≥ 1.5 x ULN.

         14. Serum creatinine ≥ 1.5 x ULN

         15. Neutrophil count < 1.0 x 109/L; platelet count < 100 x 109/L; Hb ≤ 90g/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.