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A Phase II Clinical Trial of BMS-247550 (NSC 710428), an Epothilone B Analog, in Renal Cell Carcinoma

Phase 2
18 Years
Not Enrolling
Renal Cell Carcinoma

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Trial Information

A Phase II Clinical Trial of BMS-247550 (NSC 710428), an Epothilone B Analog, in Renal Cell Carcinoma


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.


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

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


Age greater than 18.

Pathological confirmation of renal cell carcinoma.

Prior chemotherapy including sorafenib and sunitinib is allowed.


Phase II study.

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

Restaging will be done every two cycles.

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

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.


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

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.

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response Rate

Outcome Description:

Response rate is the percentage of participants with a response assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is disappearance of all target lesions, Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions,progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions or the appearance of one or more new lesions, stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Outcome Time Frame:

6 weeks

Safety Issue:


Principal Investigator

Tito Fojo, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute, National Institutes of Health


United States: Federal Government

Study ID:




Start Date:

February 2002

Completion Date:

June 2012

Related Keywords:

  • Renal Cell Carcinoma
  • Epothilone B
  • Ixabepilone
  • Renal Cell Carcinoma
  • Kidney Cancer
  • Carcinoma
  • Carcinoma, Renal Cell
  • Kidney Neoplasms



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