Clinical trial NCT00030992
Conditions: Renal Cell Carcinoma
Keywords: Epothilone B Ixabepilone Renal Cell Carcinoma Kidney Cancer
Sponsor: National Cancer Institute (NCI)
Start date: 2002-02-01; Completion date: 2012-06-01
Enrollment: 102 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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 For this procedure, a small piece of tumor tissue is withdrawn through a needle under local anesthetic.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.

Detailed description:
Background:

BMS-247550 (NSC 710428), (ixabepilone) is a semi-synthetic analog of the natural product epothilone B.

The epothilones are a novel class of non-taxane microtubule-stabilizing agents obtained from the fermentation of the cellulose degrading myxobacteria, Sorangium cellulosum.

BMS-247550 is active against cancer models that are naturally insensitive to paclitaxel or have developed resistance to paclitaxel, both in-vitro and in-vivo.

Objectives

Establish the efficacy of the investigational agent BMS-247550 in patients with renal cell carcinoma when administered as a one hour infusion on day 1 to 5 every 21 days.

Evaluate the plasma pharmacokinetics of BMS-247550.

Explore the pharmacodynamics of BMS-247550 using an assay that measures the amount of endogenous tubulin in peripheral blood mononuclear cells (PBMC) that exists in the polymerized versus the unpolymerized state.

Determine the extent to which pharmacodynamic changes are observed over a range of doses of BMS-247550.

Determine if cross-resistance to BMS-247550 exists in patients who have previously received sorafenib or sunitinib.

Eligibility:

Age greater than 18.

Pathological confirmation of renal cell carcinoma.

Prior chemotherapy including sorafenib and sunitinib is allowed.

Design:

Phase II study.

BMS-247550 will be administered on days 1 through 5, every 21 days.

Restaging will be done every two cycles.

Arms: arm 1: 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
Interventions: intervention 1: BMS-247550 intervention 2: Ranitidine intervention 3: Diphenhydramine
Intervention descriptions: intervention 1: 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 intervention 2: 50 mg 30-60 minutes prior to Ixabepilone (BMS-247550) intervention 3: 50 mg intravenously 30-60 minutes prior to Ixabepilone (BMS-247550)

Protocol documents: