Combination Sunitinib and Gemcitabine in Sarcomatoid and/or Poor-risk Patients With Metastatic Renal Cell Carcinoma

• Participants will receive study treatment as an outpatient. Study treatment will be given in 3-week cycles.
• Sunitinib will be taken orally once per day for the first two weeks (days 1-14) of each treatment cycle.
• Gemcitabine will be given intravenously at the study clinic on days 1 and 8 of each treatment cycle.
• Before receiving sunitinib and gemcitabine on day 1 of each cycle the following will be performed: physical exam, performance status assessment and blood work. Before receiving gemcitabine on day 8 the following will be performed: physical exam, performance status assessment and blood work. Every 3 cycles a CT scan will be performed to measure the tumor.

• Renal Cell Carcinoma
• Neoplasm Metastases

• Drug: Gemcitabine
  Intravenously on days 1 and 8 of each 21-day treatment cycle.
  Other Name: Gemzar
• Drug: Sunitinib
  Orally on days 1-14 of each 21-day treatment cycle
  Other Name: Sutent

Inclusion Criteria:

• Histologically proven metastatic renal cell carcinoma with any sarcomatoid histology or poor-risk features as defined by having 3 or more of the following characteristics:

  • PS > 1, high serum lactate dehydrogenase
  • low hemoglobin
  • high "corrected" serum calcium
  • 2 or more sites of metastatic disease
  • time from initial diagnosis to evidence of metastatic disease 12 months or less
• Evidence of unidimensional measurable disease based on RECIST criteria, with at least 1 measurable lesion
• Male or female, 18 years of age or older
• ECOG performance status of 0-2
• Patients with brain metastasis can only be included of they were treated 4 weeks or more prior to enrollment with whole brain radiation and the effects of treatment have resolved
• Resolution of all acute toxic effects of prior therapy, radiotherapy or surgical procedure to NCI CTCAE version 3.0 grade of 1 or less
• Laboratory values as outlined in the protocol
• 2 weeks or more must have elapsed from the time of major surgery or radiation therapy prior to the day of registration
• No anticipated need for major surgical procedure during the course of the study

Exclusion Criteria:

• Prior treatment with sunitinib or gemcitabine
• More than one prior systemic therapy of any kind for renal cell carcinoma
• Uncontrolled high blood pressure
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, or symptomatic congestive heart failure
• Ejection fraction < 30%
• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
• NCT CTCAE grade 3 or higher hemorrhage within 4 weeks of starting treatment
• Significant vascular disease
• Current grade 3 or higher cardiac dysrhythmia or QT prolongation
• Concurrent use of proarrhythmic medications including terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide, and flecainide
• Pregnancy or breastfeeding or inadequate contraception
• Evidence of bleeding diathesis or coagulopathy
• Serious, non-healing wound, ulcer or bone fracture
• Psychiatric illness/social situation that would limit compliance with study requirements
• Previous diagnosis of concurrent malignancy requiring active systemic therapy

• Pfizer
• Beth Israel Deaconess Medical Center
• Dana-Farber Cancer Institute