Neoadjuvant Axitinib in Locally Advanced Renal Cell Carcinoma (RCC)
Condition: Kidney Cancer
MeSH terms: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms
Intervention: Axitinib
Intervention description: Starting dose: 5 mg by mouth twice each day for 12 weeks.
Intervention MeSH terms: Axitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Locally advanced clear cell renal cell carcinoma; AG-013736; Axitinib; Radical nephrectomy

Summary:

      The goal of this clinical research study is to learn if axitinib can help to control kidney
      cancer. The safety of this drug will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Locally advanced renal cell carcinoma without evidence of metastatic disease with
             absence of adjacent organ invasion or retroperitoneal adenopathy (cT2-T3b, N0, M0).
             Patients with retroperitoneal lymph nodes </= 2cm in size each are considered N0.

          2. Predominant clear cell histology on pre-treatment biopsy of the primary tumor.

          3. Patient should be candidate for curative radical nephrectomy.

          4. ECOG Performance Status 0-1.

          5. Patient must provide signed informed consent.

          6. Male or female, age >/= 18 years.

          7. Adequate renal function: serum creatinine level </=1.5 x ULN or calculated creatinine
             clearance (as estimated by GFR using the MDRD formula) is >/= 60 ml/min.

          8. Adequate hepatic function: alkaline phosphatase </= 1.5 x ULN; total bilirubin, AST,
             and ALT </= 1.5 x ULN; INR <1.3 (or <3 if on anticoagulant therapy).

          9. Adequate bone marrow function: ANC >/= 1.5 x 10/ 9L; Platelets >/= 100 x 109/L; Hb >9
             g/dL

         10. Urinary protein <100 on urinalysis (equivalent to <2+ by urine dipstick). If
             urinalysis protein >/=100 (equivalent to dipstick is >/=2+) then a 24-hour urine
             collection can be done and the patient may enter only if urinary protein is <2 g per
             24 hours

         11. No hormonal therapy, chemotherapy, immunotherapy, or any other systemic therapy for a
             malignancy, in the 5 years prior to current study enrollment.

         12. Women of childbearing potential (defined as a female subject who is not surgically
             sterilized, not at least 1 year postmenopausal) must have negative urine or serum
             pregnancy test within 4 weeks of enrollment and again on the day of starting therapy
             and she and/or her partner must utilize birth control while on therapy.

         13. Male (defined as a male subject who has not been surgically sterilized) or female
             patients of child-producing potential must agree to use adequate contraception (e.g.
             IUD, condom plus spermicide, diaphragm, or cervical cap plus spermicide) or medical
             contraception: as of date of study enrollment and for at least 1 month after last dose
             of axitinib. Subjects who are not currently sexually active must agree and consent to
             use one of the above-mentioned methods should they become sexually active while
             participating in the study.

        Exclusion Criteria:

          1. Evidence of metastatic disease, adjacent organ invasion, retroperitoneal adenopathy on
             pre-treatment imaging. In addition, patients with inferior vena cava thrombi extending
             to the atrium or with evidence of Budd-Chiari Syndrome (hepatic dysfunction) will not
             be eligible for the protocol.

          2. Patients who undergo embolization of their primary tumor.

          3. Previous treatment for their primary renal tumor, including prior chemotherapy,
             immunotherapy, targeted therapy, radiation therapy, cryotherapy, radiofrequency
             ablation or embolization.

          4. Active malignancies other than renal cell carcinoma and/or history of other malignancy
             within the last 5 years, except for adequately treated cone-biopsied in situ carcinoma
             of the cervix or basal or squamous cell carcinoma of the skin

          5. Uncontrolled hypertension (BP>140/90 on medications), 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.

          6. Current use or anticipated need for treatment with drugs that are known potent CYP3A4
             inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole,
             erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir,
             nelfinavir, nefazodone, lopinavir, atazanavir, amprenavir, fosamprenavir and
             delavirdine).

          7. Current use or anticipated need for treatment with drugs that are known potent CYP3A4
             or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole,
             phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and
             St. John's wort).

          8. Active gastrointestinal bleeding.

          9. Malabsorption syndromes such as celiac disease, cystic fibrosis, inflammatory bowel
             disease, systemic sclerosis, and carcinoid syndrome.

         10. Known HIV or Hepatitis C status.

         11. Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose
             anticoagulants for maintenance of patency of central venous access devise or
             prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular
             weight heparin is allowed.

         12. Active seizure disorder or evidence of brain metastases, spinal cord compression, or
             carcinomatous meningitis.

         13. A serious uncontrolled medical disorder or active infection that would impair their
             ability to receive study treatment.

         14. Any of the following within the 12 months prior to study drug administration:
             myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft,
             symptomatic congestive heart failure, cerebrovascular accident or transient ischemic
             attack and 6 months for deep vein thrombosis or pulmonary embolism

         15. Withdrawal of consent.

         16. Unwillingness or inability to comply with mandated pretreatment biopsy or therapeutic
             regimen.