Adjuvant Axitinib Therapy of Renal Cell Cancer in High Risk Patients

Adjuvant Axitinib Treatment of Renal Cancer: A Randomized Double-blind Phase 3 Study of Adjuvant Axitinib vs. Placebo in Subjects at High Risk of Recurrent RCC

The purpose of this trial is to determine if adjuvant therapy with axitinib will prevent or delay the recurrence of renal cell cancer after surgery to remove the primary tumor in high risk patients.

This is a prospective, randomized, double blind placebo controlled Phase 3 trial of oral axitinib starting at 5 mg twice daily given 3 years vs. placebo.

Approximately 700 patients will be randomized in a 1:1 ratio between axitinib vs placebo.

Inclusion Criteria:

Patients must be treated by nephrectomy and patients must meet all of the following inclusion criteria to be eligible for enrollment into the trial:

1. Patients must have no evidence of macroscopic residual disease or metastatic disease.

2. Male or female, age >=18 years (age >=20 years in Japan, Korea and Taiwan).

3. Patients must be diagnosed with one of the following based on American Joint Committee on Cancer (AJCC) TNM staging version 2010, Eastern Collaborative Oncology Group (ECOG) performance status (PS):

   • pT2, pN0 or pNx, M0 and ECOG PS 0-1
   • pT3, pN0 or pNx, M0 and ECOG PS 0-1
   • pT4, pN0 or pNx, M0 and ECOG PS 0-1
   • Any pT, pN1, M0 and ECOG PS 0-1

4. Patients must have histologically confirmed preponderant, defined as >50%, clear cell RCC.

5. Patients must not have received any previous systemic (includes chemotherapeutic, hormonal, or immunotherapeutic) treatment for RCC.

6. Patients must not have received any previous anti angiogenic treatment.

7. Patients must have adequate organ function.

Exclusion Criteria

1. Histologically undifferentiated carcinomas, sarcomas, collecting duct carcinoma, lymphoma, or patients with any metastatic renal sites.
2. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 hemorrhage <4 weeks of date of randomization.
3. Diagnosis of any non-RCC malignancy within the 5 years from date of randomization, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma of the cervix uteri that has been adequately treated with no evidence of recurrent disease for 12 months.
4. 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.
5. Gastrointestinal abnormalities