SLM + Axitinib for Clear Cell RCC

This is a Phase 1 trial for safety and preliminary efficacy of the combination of axitinib
and selenomethionine (SLM) for adult patients with advanced metastatic clear cell renal cell
carcinoma (CCRCC). This will be a two part study consisting of a dose escalation and
expansion study.

Dose-Escalation Part 1 (6-12 patients) : SLM will be given twice daily for 14 days followed
by SLM once daily in combination with axitinib 5 mg twice daily with titration according to
package insert in patients with advanced renal cell carcinoma. Treatment will continue until
disease progression or unacceptable toxicity.

Expansion Part 2: In this phase (approximately 19 patients), will be treated at the maximum
tolerated dose (MTD) of SLM determined in the Escalation Part 1. It will be given orally
twice daily for 14 days, followed by SLM once daily in combination with axitinib 5 mg twice
daily with titration according to package insert in patients with advanced renal cell
carcinoma. Treatment will continue until disease progression or unacceptable toxicity.

Inclusion Criteria:

- Histologically and radiologically confirmed advanced metastatic CCRCC in patients who
have had at least one prior systemic therapy, which can include axitinib for the dose
escalation part. In the expansion part, patients with prior axitinib use will be
excluded.

- Written and voluntary informed consent.

- At least one Response Evaluation Criteria In Solid Tumors (RECIST)-defined target
lesion. *Patient must have documented disease progression.

- Renal function (creatinine level within normal institutional limit, or creatinine
clearance >15 mL/min/1.73 m2 for patients with creatinine levels above institutional
normal, calculated using the Cockcroft-Gault formula).

- Liver function (AST/ALT <2.5 X institutional upper limit of normal OR <5 X
institutional upper limit of normal in cases of liver metastases; Total bilirubin ≤
1.5 times ULN.)

- Adequate hematological lab values including: Absolute Neutrophil Count (ANC) ≥ 1.0 x
109/L, Platelets ≥ 100 x 109/L, Hemoglobin ≥ 9.0 g/dL

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 (fully active, able
to carry on all pre-disease performance without restriction) or 1 (restricted in
physically strenuous activity but ambulatory and able to carry out work of a light or
sedentary nature, such as light housework or office work) or 2 (Ambulatory and capable
of all self-care but unable to carry out any work activities; up and about more than
50% of waking hours).

- Age of at least 18 years.

- Life expectancy of 12 weeks and more.

- 2 weeks or more since end of previous systemic treatment (4 weeks or more for
bevacizumab plus interferon-alfa). 3 days wash out for palliative radiation.

Exclusion Criteria:

- Any other cancer from which the patient has been disease-free for less than 5 years
(except treated and cured basal-cell or squamous-cell skin cancer, superficial bladder
cancer, or treated carcinoma in situ of the cervix, breast, or bladder and treated
localized prostate cancer with undetectable PSA for 2 years).

- Symptomatic untreated metastases in the central nervous system.

- Subject that is pregnant or lactating

- Pre-existing uncontrolled hypertension defined as > 150/90 mm Hg with medication.

- Present use or anticipated need for cytochrome P450 (CYP) 3A4-inhibiting,
CYP3A4-inducing drugs (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir,
indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and
voriconazole, rifampin, phenytoin, carbamazepine, rifabutin, rifapentin,
phenobarbital, and St. John's wort, bosentan, efavirenz, etravirine, modafinil, and
nafcillin).Myocardial infarction, uncontrolled angina, congestive heart failure, or
cerebrovascular accident within previous 6 months. Subjects with history of deep vein
thrombosis or pulmonary embolism, at provider discretion.

- Myocardial infarction, uncontrolled angina, congestive heart failure, or
cerebrovascular accident within previous 12 months; and deep vein thrombosis or
pulmonary embolism within previous 6 months.

- Major surgery within 4 weeks of starting study treatment.

- Known HIV or acquired immunodeficiency syndrome-related disease.