BMS 247550 to Treat Kidney Cancer
Condition: Renal Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Renal Cell
Intervention: BMS-247550; Ranitidine; Diphenhydramine
Intervention description: One hour infusion on five successive days (daily x 5) every three weeks. Starting dose of 6 mg/m^2/day for a total per cycle dose of 30 mg/m^2; 50 mg 30-60 minutes prior to Ixabepilone (BMS-247550); 50 mg intravenously 30-60 minutes prior to Ixabepilone (BMS-247550)
Intervention MeSH terms: Diphenhydramine; Promethazine; Ranitidine; Ranitidine bismuth citrate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Epothilone B; Ixabepilone; Renal Cell Carcinoma; Kidney Cancer

Summary:

      This study will examine whether the experimental drug BMS 247550 (Ixabepilone) is an
      effective treatment for kidney cancer. BMS 247550 belongs to a class of drugs called
      epothilones that interfere with the ability of cancer cells to divide. In the way they kill
      cells, they are very similar to a class of compounds known as the taxanes, which include the
      drug Taxol. Other characteristics of the epothilones, however, enable them to work in cells
      that are resistant to Taxol.

      Patients 18 years of age or older with kidney cancer that has not spread to the central
      nervous system (unless the brain tumor has remained stable for at least six months after
      surgical or radiation treatment) may be eligible for this study. Pregnant or nursing women
      may not participate. Candidates are screened with various tests that may include blood and
      urine tests, electrocardiogram (EKG), and chest x-ray. Computerized tomography (CT) scans or
      X-rays, and possibly nuclear medicine studies may be done to determine the extent of disease.

      Participants receive BMS 247550 by a 1-hour infusion into a vein for 5 consecutive days (days
      1, 2, 3, 4 and 5) of each 21-day treatment cycle. Patients must stay in the National
      Institutes of Health (NIH) area near Bethesda, Maryland, for 7 to 8 days during the first
      treatment cycle and for the 5 days of treatment in subsequent cycles. The total number of
      cycles will vary among patients, depending on their individual clinical situation. The drug
      dose may be increased gradually in subsequent cycles in patients who can tolerate such
      increases. In addition, participants undergo the following tests and procedures:

        -  Periodic physical examinations and frequent blood tests

        -  X-ray and other imaging studies to determine if the tumor is responding to the
           treatment.

        -  Tumor biopsies to confirm the diagnosis or spread of tumor and to examine the reaction
           of certain proteins in cancer cells to BMS 247550. Two biopsies will be done. For this
           procedure, a small piece of tumor tissue is withdrawn through a needle under local
           anesthetic.

      Treatment will be stopped in patients whose tumor grows while receiving BMS 247550. Patients
      whose tumor disappears completely will be followed at NIH periodically for examinations and
      tests. Patients whose disease does not completely resolve or whose disease recurs may be
      advised of other appropriate research protocols at NIH or, if none are available, will be
      returned to the care of their local doctor.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Patients must fulfill all of the following criteria to be eligible for study admission:

          1. Age greater than or equal to 18 years.

          2. Histologic or cytologic confirmation of renal cell carcinoma (clear cell, type I and
             type II papillary, chromophobe, collecting duct and medullary).

             Patients should either:

               1. have received interleukin-2 (IL-2);

               2. have been evaluated for therapy with IL-2 and deemed to be ineligible; or (c)
                  have been evaluated for therapy with IL-2 and refused treatment.

          3. Measurable extent of disease.

          4. Performance Status Eastern Cooperative Oncology Group (ECOG) 0-2.

          5. Life expectancy of 3 months or greater.

          6. Suitable candidate for receiving planned therapy as evidenced by screening laboratory
             assessments of hematologic, renal, hepatic, and metabolic functions:

             platelet count greater than or equal to 100,000/mL, absolute granulocyte count (AGC)
             greater than or equal to 1,500/mL, serum creatinine less than or equal to 1.6 or a
             measured creatinine clearance greater than or equal to 40 ml/min, serum glutamic
             pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) less
             than or equal to 2.5 x normal limit (NL), and total bilirubin less than or equal to
             1.5 x NL (in patients with clinical evidence of Gilberts' disease, less than or equal
             to 3 x NL).

          7. Greater than or equal to 4 weeks from prior cytotoxic chemotherapy, radiation or
             immunotherapy; greater than or equal to 2 weeks from prior targeted-therapy
             (cytostatic agents); such patients should have recovered from toxicity from the prior
             therapy.

          8. No serious intercurrent medical illness.

          9. The ability to understand and willingness to sign a written informed consent form, and
             to comply with the protocol.

         10. Patients should either: (a) have received sorafenib and or sunitinib and had
             progressive disease while receiving the drug(s) or (b) been intolerant to the
             drugs(s), or (c) been evaluated for therapy with sorafenib and or sunitinib and deemed
             to be ineligible; or (d) have been evaluated for therapy with sorafenib and or
             sunitinib and refused treatment.

        EXCLUSION CRITERIA:

        Patients with any of the following will be excluded from study entry:

          1. Pregnant or nursing women are not eligible; neither are women or men of childbearing
             potential unless using effective contraception as determined by the patient's
             physician.

          2. Patients with a history of central nervous system (CNS) metastases, because
             symptoms/signs of progressive disease may be confused with drug-related toxicities,
             unless control has been achieved with either radiation or surgical resection at least
             six months prior to enrollment on study.

          3. Patients who are poor medical risk because of other non-malignant systemic disease or
             active, uncontrolled infection.

          4. Human immunodeficiency virus (HIV) seropositive patients. Patients infected with the
             HIV virus will be excluded from this trial because the effect of BMS-247550 on HIV
             replication and/or the immune system is unknown and may be potentially harmful.

          5. Prior craniospinal radiation, or total body irradiation (TBI).

          6. Patients receiving other investigational drugs, or St. John's Wort (St. John's Wort
             can induce P450 and alter drug metabolism).

          7. Common Toxicity Criteria (CTC) Grade 2 or greater motor or sensory neuropathy.

          8. Known prior severe hypersensitivity reactions to agents containing Cremophor EL.