Combination Sunitinib and Gemcitabine in Sarcomatoid and/or Poor-risk Patients With Metastatic Renal Cell Carcinoma
Condition: Renal Cell Carcinoma; Neoplasm Metastases
MeSH terms: Carcinoma; Neoplasm Metastasis; Carcinoma, Renal Cell
Intervention: Gemcitabine; Sunitinib
Intervention description: Intravenously on days 1 and 8 of each 21-day treatment cycle.; Orally on days 1-14 of each 21-day treatment cycle
Intervention MeSH terms: Gemcitabine; Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 72.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: mRCC; sunitinib; gemcitabine

Summary:

      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.
    

Eligibility criteria:

        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