Ixabepilone in Treating Patients With Metastatic, Recurrent, or Unresectable Kidney Cancer

A Phase II Trial of BMS 247550 (Ixabepilone) in Advanced Renal Cell Carcinoma

This phase II trial is studying how well ixabepilone works in treating patients with metastatic, recurrent, or unresectable kidney cancer. Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing

Study Overview

• Status: Completed
• Conditions: Clear Cell Renal Cell Carcinoma; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer; Recurrent Renal Cell Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: ixabepilone

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the objective response rate in patients with metastatic, recurrent, or unresectable renal cell carcinoma treated with ixabepilone.

SECONDARY OBJECTIVES:

I. Determine the progression-free and overall survival rates in patients treated with this drug.

II. Determine the toxicity of this drug in these patients. III. Correlate VHL gene mutations with response in patients treated with this drug.

IV. Correlate VHL pathway protein expression with response in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 9 weeks until disease progression and then every 3 months for up to 2 years.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed renal cell carcinoma of 1 of the following subtypes:

  • Clear cell
  • Papillary, type I or II
  • Chromophobe
  • Collecting duct
  • Medullary
• Metastatic, recurrent, or unresectable disease
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

• No known active brain metastases requiring steroid or anticonvulsant therapy

  • Patients with definitively treated brain metastases are eligible provided they are not on steroids or anticonvulsants AND show no evidence of disease progression for ≥ 3 months after completion of definitive therapy
• Performance status - ECOG 0-2
• At least 3 months
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Creatinine ≤ 1.5 times ULN
• Glomerular filtration rate ≥ 50 mL/min
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No ongoing or active infection
• No HIV positivity
• No peripheral neuropathy > grade 1
• No psychiatric illness or social situation that would preclude study compliance
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to study drug
• No history of severe hypersensitivity reaction to agents containing Cremophor® EL

• No other active malignancy

  • Curatively treated malignancies are allowed provided the risk of recurrent disease at the time of study enrollment is < 20%
• No other uncontrolled illness
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

• No prior tubule inhibitors, including, but not limited to, any of the following:

  • Vinca alkaloids (e.g., vinblastine, vincristine, or vinorelbine)
  • Taxanes (e.g., docetaxel or paclitaxel)
  • Epothilones
• No other concurrent chemotherapy
• See Disease Characteristics
• No concurrent hormonal therapy except steroids for adrenal failure or hypersensitivity prophylaxis or hormones for non-disease related conditions (e.g., insulin for diabetes)
• More than 4 weeks since prior radiotherapy and recovered
• No concurrent palliative radiotherapy
• No other concurrent investigational agents
• No other concurrent anticancer therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Patients receive ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Drug: ixabepilone; Given IV; Other Names: BMS-247550; epothilone B lactam; Ixempra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (partial or complete)	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS rate will be estimated using the Kaplan-Meier method. Median PFS time and its associated 90% confidence interval will be estimated using the method of Brookmeyer and Crowley.	From the start of treatment to time of progression, assessed up to 5 years
Overall survival (OS)	OS rate will be estimated using the Kaplan-Meier method. Median OS time and its associated 90% confidence interval will be estimated using the method of Brookmeyer and Crowley.	Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Edwin Posadas, University of Chicago Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: July 1, 2005
• Primary Completion (Actual): September 1, 2007

Study Registration Dates

• First Submitted: September 15, 2005
• First Submitted That Met QC Criteria: September 15, 2005
• First Posted (Estimate): September 16, 2005

Study Record Updates

• Last Update Posted (Estimate): March 25, 2013
• Last Update Submitted That Met QC Criteria: March 22, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Epothilones; Epothilone B
• Other Study ID Numbers: NCI-2012-02669; N01CM62201 (U.S. NIH Grant/Contract); N01CM62209 (U.S. NIH Grant/Contract); 13850A; CDR0000440071 (Registry Identifier: PDQ (Physician Data Query))