Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
102 participants
INTERVENTIONAL
2002-02-28
2012-06-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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 For this procedure, a small piece of tumor tissue is withdrawn through a needle under local anesthetic.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
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
BMS-247550
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
BMS-247550
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
Ranitidine
50 mg 30-60 minutes prior to Ixabepilone (BMS-247550)
Diphenhydramine
50 mg intravenously 30-60 minutes prior to Ixabepilone (BMS-247550)
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
BMS-247550
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
Ranitidine
50 mg 30-60 minutes prior to Ixabepilone (BMS-247550)
Diphenhydramine
50 mg intravenously 30-60 minutes prior to Ixabepilone (BMS-247550)
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
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
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.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
National Institutes of Health
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Tito Fojo, M.D.
Role: PRINCIPAL_INVESTIGATOR
National Cancer Institute, National Institutes of Health
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Wilson L, Jordan MA. Microtubule dynamics: taking aim at a moving target. Chem Biol. 1995 Sep;2(9):569-73. doi: 10.1016/1074-5521(95)90119-1.
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. doi: 10.3109/07357909509031919.
Von Hoff DD. The taxoids: same roots, different drugs. Semin Oncol. 1997 Aug;24(4 Suppl 13):S13-3-S13-10.
Huang H, Menefee M, Edgerly M, Zhuang S, Kotz H, Poruchynsky M, Huff LM, Bates S, Fojo T. A phase II clinical trial of ixabepilone (Ixempra; BMS-247550; NSC 710428), an epothilone B analog, in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2010 Mar 1;16(5):1634-41. doi: 10.1158/1078-0432.CCR-09-0379. Epub 2010 Feb 23.
Related Links
Access external resources that provide additional context or updates about the study.
NIH Clinical Center Detailed Web Page
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
02-C-0130
Identifier Type: -
Identifier Source: secondary_id
020130
Identifier Type: -
Identifier Source: org_study_id
NCT00033670
Identifier Type: -
Identifier Source: nct_alias