BMS 247550 to Treat Kidney Cancer - Full Text View

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00030992

Purpose

This study will examine whether the experimental drug BMS 247550 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 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 For this procedure, a small piece of tumor tissue is withdrawn through a needle under local anesthetic.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.

Condition	Intervention	Phase
Renal Cell Carcinoma	Drug: BMS-247550	Phase II

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Clinical Trial of BMS-247550 (NSC 710428), an Epothilone B Analog, in Renal Cell Carcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Kidney Cancer

Drug Information available for: Epothilone B Ixabepilone

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

Activity [ Designated as safety issue: No ]
Plasma pharmacokinetics and pharmacodynamics [ Designated as safety issue: No ]
Nerve growth factor (NGF) levels [ Designated as safety issue: No ]
Correlation of NGF levels with neurotoxicity [ Designated as safety issue: Yes ]
Differences between responding and non-responding tumors as assessed by cDNA microarray [ Designated as safety issue: No ]

Secondary Outcome Measures:

Determine the extent to which pharmacodynamic changes are observed over a range of doses of ixabepilone.
Determine if cross-resistance to ixabepilone exists in patients who have received prior sorafenib or sunitinib.

Enrollment:	102
Study Start Date:	February 2002
Estimated Study Completion Date:	December 2012
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Intervention Details:

N/A

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 than18.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

INCLUSION CRITERIA:

Patients must fulfill all of the following criteria to be eligible for study admission:

Age greater than or equal to 18 years.
Histologic or cytologic confirmation of renal cell carcinoma (clear cell, type I and type II papillary, chromophobe, collecting duct and medullary). Patients should either: (a) have received IL-2; (b) 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.
Measurable extent of disease.
Performance Status ECOG 0-2.
Life expectancy of 3 months or greater.
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, SGPT and SGOT less than or equal to 2.5 x 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).
Greater than or equal to 4 weeks from prior cytotoxic chemothrapy, 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.
No serious intercurrent medical illness.
The ability to understand and willingness to sign a written informed consent form, and to comply with the protocol.
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:

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.
Patients with a history of 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.
Patients who are poor medical risk because of other non-malignant systemic disease or active, uncontrolled infection.
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.
Prior craniospinal radiation, or total body irradiation (TBI).
Patients receiving other investigational drugs, or St. John's Wort (St. John's Wort can induce P450 and alter drug metabolism).
CTC Grade 2 or greater motor or sensory neuropathy.
Known prior severe hypersensitivity reactions to agents containing Cremophor EL.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00030992

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Cancer Institute (NCI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

Wilson L, Jordan MA. Microtubule dynamics: taking aim at a moving target. Chem Biol. 1995 Sep;2(9):569-73. Review.

Huizing MT, Misser VH, Pieters RC, ten Bokkel Huinink WW, Veenhof CH, Vermorken JB, Pinedo HM, Beijnen JH. Taxanes: a new class of antitumor agents. Cancer Invest. 1995;13(4):381-404. Review.

Von Hoff DD. The taxoids: same roots, different drugs. Semin Oncol. 1997 Aug;24(4 Suppl 13):S13-3-S13-10. Review.

Responsible Party:	Antonio T. Fojo, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier:	NCT00030992 History of Changes
Obsolete Identifiers:	NCT00033670
Other Study ID Numbers:	020130, 02-C-0130
Study First Received:	February 20, 2002
Last Updated:	January 7, 2012
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Epothilone B
Ixabepilone
Renal Cell Carcinoma
Kidney Cancer

Additional relevant MeSH terms:

Carcinoma
Kidney Neoplasms
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases

Adenocarcinoma
Epothilone B
Epothilones
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 13, 2012