A Randomized Phase II Study to Explore the Efficacy and Feasibility of Upfront Bi-monthly Rotations Between Everolimus and Pazopanib in Patients With Advanced or Metastatic Clear Cell Renal Cancer
- Subjects must provide written informed consent prior to performance of study-specific
procedures or assessments, and must be willing to comply with treatment and
- Age ≥ 18 years.
- Histologically confirmed diagnosis of progressive metastatic clear cell renal cell
cancer defined as >10% of the tumor cells having the clear cell phenotype.
- Locally advanced (defined as disease not amenable to curative surgery or radiation
therapy) or metastatic RCC (equivalent to Stage IV RCC according to AJCC staging).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Measurable disease.
- No prior systemic anti-cancer treatment against clear cell renal carcinoma.
- Adequate organ system function.
- Non-childbearing potential.
- Prior malignancy.
- History or clinical evidence of central nervous system (CNS) metastases or
- Clinically significant gastrointestinal abnormalities that may increase the risk for
- Clinically significant gastrointestinal abnormalities that may affect absorption of
- Presence of uncontrolled infection.
- Known past or present infection with Hepatitis B virus (HBV), Hepatitis C virus (HCV)
or Human Immunodeficiency Virus (HIV).
- Corrected QT interval (QTc) > 480 msecs using Bazett's formula.
- History of one or more of the following cardiovascular conditions within the past 6
1. Cardiac angioplasty or stenting
2. Myocardial infarction
3. Stable or unstable angina pectoris.
4. Coronary artery bypass graft surgery.
5. Symptomatic peripheral vascular disease
6. Class III or IV congestive heart failure, as defined by the New York Heart
- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg
or diastolic blood pressure (DBP) of ≥ 90mmHg].
- History of cerebrovascular accident including transient ischemic attack (TIA),
pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6
- Prior major surgery or trauma within 28 days prior to first dose of study drug and/or
presence of any nonhealing wound, fracture, or ulcer (procedures such as catheter
placement not considered to be major).
- Evidence of active bleeding or bleeding diathesis.
- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
- Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of
- Any serious and/or unstable pre-existing medical, psychiatric, or other condition
that could interfere with subject's safety, provision of informed consent, or
compliance to study procedures.
- Unable or unwilling to discontinue use of prohibited medications or modify the dosing
of interacting drugs for at least 14 days or five half-lives of a drug (whichever is
longer) prior to the first dose of study drug and for the duration of the study.
- Pregnant or lactating female.
- Treatment with any of the following anti-cancer therapies: Radiation therapy, surgery
or tumor embolization within 14 days prior to the first dose of Pazopanib OR
Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal