Sunitinib Malate With or Without Gemcitabine Hydrochloride in Treating Patients With Advanced Kidney Cancer That Cannot Be Removed By Surgery
Condition: Kidney Cancer
MeSH terms: Carcinoma, Renal Cell; Kidney Neoplasms
Intervention: Gemcitabine; Sunitinib
Intervention description: Given IV; Given PO
Intervention MeSH terms: Gemcitabine; Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 87.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: recurrent renal cell cancer; stage IV renal cell cancer; clear cell renal cell carcinoma; papillary renal cell carcinoma; clear cell sarcoma of the kidney

Summary:

      RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth or by blocking blood flow to the tumor. Drugs used in
      chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth or
      tumor cells, either by killing the cells or by stopping them from dividing. It is not yet
      known whether giving sunitinib malate and gemcitabine hydrochloride together is more
      effective than sunitinib malate alone in treating patients with kidney cancer.

      PURPOSE: This randomized phase II clinical trial is studying giving sunitinib malate together
      with or without gemcitabine hydrochloride to see how well they work in treating patients with
      advanced kidney cancer that cannot be removed by surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed* renal cell carcinoma of any subtype containing any
             sarcomatoid features NOTE: *Patients must have a paraffin-embedded tumor specimen from
             the kidney or metastatic site available for central review and confirmation of tumor
             histology

          -  Measurable advanced disease that is not resectable by surgery

          -  Patients with resected or radiated brain metastases or those treated with stereotactic
             radiation therapy are eligible, provided they have been off steroids for at least 2
             weeks

          -  More than 2 weeks since prior radiotherapy and recovered

               -  Previously irradiated lesions must not be the sole site of disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Absolute neutrophil count (ANC) ≥ 1,500/mm^3

          -  Platelet count ≥ 100,000/mm^3

          -  Hemoglobin ≥ 9.0 g/dL (transfusions allowed)

          -  Serum creatinine clearance ≥ 30 mL/min

          -  serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase
             (SGPT) ≤ 2.5 times upper limit of normal (ULN; ≤ 5 times ULN in the presence of liver
             metastases)

          -  Total bilirubin ≤ 1.5 times ULN

          -  Baseline corrected QT interval < 500 msec on EKG

          -  Able to swallow pills

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception before and during study treatment

          -  More than 2 weeks since prior and no concurrent ketoconazole, dexamethasone,
             dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucol, bepridil,
             indapamide, or flecainide), haloperidol, risperidone, rifampin, grapefruit, or
             grapefruit juice

          -  Patients with a history of prior malignancy are eligible provided they were treated
             with curative intent and have been disease free for the time period considered
             appropriate to not interfere with the outcome of this study

        Exclusion Criteria:

          -  Collecting duct or medullary carcinoma

          -  Prior systemic therapy for metastatic disease. One prior therapeutic regimen with a
             non-tyrosine kinase inhibitor, such as an mtor inhibitor is allowed. Patients who were
             randomized to placebo on an adjuvant study are eligible

          -  History of stroke within the past 6 months.

          -  Pregnant or nursing

          -  Clinically significant cardiovascular disease, defined as one of the following:

               -  Uncontrolled hypertension (blood pressure > 150/100 mm Hg at the time of
                  enrollment); patients with hypertension and BP ≤ 150/100 mm Hg on stable
                  antihypertensive regimen are eligible

               -  History of myocardial infarction or unstable angina within the past 24 weeks

               -  New York heart association grade II or greater congestive heart failure, serious
                  cardiac arrhythmia requiring medication, unstable angina pectoris

               -  Peripheral vascular disease ≥ grade II

          -  Ongoing ventricular cardiac dysrhythmias ≥ grade 2 as assessed by National Cancer
             Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4

          -  History of serious ventricular arrhythmia (ventricular tachycardia or ventricular
             fibrillation > 3 beats in a row)

          -  Ongoing atrial fibrillation

          -  Pre-existing thyroid abnormality with thyroid-stimulating hormone that cannot be
             maintained at less than or within the normal range with medication

          -  Serious concurrent illness or active infection that would jeopardize the ability of
             the patient to receive study treatment

          -  Known HIV