Prior Axitinib as a Determinant of Outcome of Renal Surgery

The primary objective of the study is to prospectively assess utility of axitinib in
facilitation of partial nephrectomy where partial nephrectomy was not thought to be
safe/possible in the setting of imperative indication for complex renal masses in renal cell
cancer.

Secondary objectives: To determine the safety, tumor diameter (per RECIST v1.1) volume
change, surgical morbidity and renal functional outcomes following neoadjuvant axitinib for
RCC.

Anatomical/morphometric:

1. tumor diameter/volume change,

2. conversion of hilar to non-hilar tumors,

3. reduction in RENAL morphometric score.

Functional Considerations:

1. Requirement of acute dialysis

2. Change in Glomerular Filtration Rate (GFR)

3. Whether or not GFR crosses 30 threshold, or decline by GFR to >50% of baseline.

Safety indices:

1. Incidence of Clavien >3 complications

2. Avoidance of need for multiple blood transfusions

Inclusion Criteria:

1. Localized clear cell renal carcinoma without evidence of distant metastases

2. Imperative indication for nephron sparing surgery

- Baseline chronic kidney disease (CKD) (stage 3, GFR <60 ml/min/1.73m2), or
anatomically or functional solitary kidney (defined by renal scintigraphy of
contralateral renal unit with <15% function) or bilateral synchronous disease);
and

- RENAL score ≥10 or proximity to renal hilum (defined as <2 mm away from at least
2 renal hilar vessels-the main artery/vein or first order branches); and

- Radical nephrectomy would lead to severe CKD (stage 3b, GFR <45 ml/min/1.73m2).

3. Male or female, age ≥ 18 years

4. Karnofsky performance status ≥ 70.

5. Adequate organ function as defined by:

- Absolute neutrophil count (ANC) ≥1,000/μL

- Platelets ≥100,000/μL

- Hemoglobin ≥9.0 g/dL

- Serum calcium ≤12.0 mg/dL

- Serum creatinine ≤1.5 x upper limit of normal (ULN)

- Total serum bilirubin ≤1.5 x ULN

- SGOT≤2.5 x ULN and serum glutamic pyruvic transaminase (SGPT) ≤2.5x ULN

6. Signed informed consent and willingness/ability to comply with scheduled visits,
treatment plans, laboratory tests, and other study procedures

Exclusion Criteria:

1. Presence of metastatic disease on radiographic imaging.

2. Elective indication for nephron sparing surgery

3. Non-clear cell histology

4. Prior systemic treatment of any kind or radiotherapy for RCC

5. NCI CTCAE Version 5.0 grade 3 hemorrhage within 4 weeks of starting the study
treatment

6. Ongoing cardiac dysrhythmias of NCI CTCAE Version 5.0 grade ≥2. Controlled atrial
fibrillation is permitted. Prolonged corrected QT interval by the Fridericia
correction formula (QTcF) on screening EKG >480 msec.

7. Pregnancy or breastfeeding. Female subjects must be surgically sterile or be
postmenopausal,or must agree to use effective contraception during the period of
therapy. All female subjects with reproductive potential must have a negative
pregnancy test (serum) prior to enrollment. Male subjects must be surgically sterile
or must agree to use effective contraception during the period of therapy. The
definition of effective contraception will be based on the judgment of the principal
investigator or a designated associate.

8. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, or may interfere with the interpretation of study results, and in
the judgment of the investigator would make the subject inappropriate for entry into
this study.

9. Uncontrolled hypertension (HTN): systolic blood pressure ≥150 or diastolic blood
pressure ≥ 100 mmHg or both despite appropriate therapy.

10. HTN with need for greater than three anti-hypertensive agents at baseline. Drug
formulations containing two or more anti-hypertensive agents will be counted based on
the number of active agents in each formulation.

11. New York Heart Association (NYHA) class III or greater congestive heart failure (CHF)

12. Uncontrolled hyper- or hypothyroidism.

13. Subjects with arterial thrombotic events in the prior 12 months (axitinib has never
been studied in this population)

14. Subjects who have had venous thrombotic events in the prior 6 months (axitinib has
never been studied in this population)