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

• To determine the time to tumor progression (TTP) of combination therapy with gemcitabine and sunitinib in this patient population. [ Time Frame: Until disease progression ] [ Designated as safety issue: No ]
• To evaluate the safety and tolerability of this treatment in mRCC patients. [ Time Frame: Until disease progression ] [ Designated as safety issue: Yes ]
• To determine the overall survival of this treatment in mRCC patients. [ Time Frame: Lifetime ] [ Designated as safety issue: No ]
• To collect serum research samples for analysis of predictive biomarkers of response. [ Time Frame: Until disease progression ] [ Designated as safety issue: No ]

• To determine the time to tumor progression (TTP) of combination therapy with gemcitabine and sunitinib in this patient population. [ Time Frame: Until disease progression ]
• To evaluate the safety and tolerability of this treatment in mRCC patients. [ Time Frame: Until disease progression ]
• To determine the overall survival of this treatment in mRCC patients. [ Time Frame: Lifetime ]
• To collect serum research samples for analysis of predictive biomarkers of response. [ Time Frame: Until disease progression ]

The purpose of this research study is to determine if the combination of sunitinib and gemcitabine is effective in treating patients with metastatic renal cell carcinoma. The safety of this combination will also be studied. Sunitinib is approved by the FDA for the treatment of renal cell carcinoma. However, some patients' cancers do not respond to treatment or stops responding after initially responding. Gemcitabine is a chemotherapy drug that is approved by the FDA for the treatment of pancreatic cancer and several other cancers. It is not approved for the treatment of renal cell carcinoma. Previous research has suggested that combining gemcitabine with sunitinib may have some effectiveness in treating 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