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BMS-247550 Plus Carboplatin in Treating Patients With Recurrent or Refractory Solid Tumors

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Terminated
CT.gov ID
NCT00028561
Collaborator
(none)
45
Enrollment
1
Location
1
Arm

Study Details

Study Description

Brief Summary

This phase I trial is studying the side effects and best dose of BMS-247550 when given together with carboplatin in treating patients with recurrent or refractory solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

OBJECTIVES:

  1. Determine the maximum tolerated dose of BMS-247550 when given in combination with carboplatin in patients with recurrent or refractory solid tumors.

  2. Determine the dose-limiting toxicity and safety of this regimen in these patients.

  3. Determine the plasma pharmacokinetics of this regimen in these patients. IV. Determine, preliminarily, any antitumor activity of this regimen in these patients.

  4. Correlate the protein expression of survivin with the expression of other apoptotic regulators, the apoptotic index, and response in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of BMS-247550.

Patients receive BMS-247550 IV over 1 hour on days 1, 8, and 15 followed by carboplatin IV over 1 hour on day 1. Treatment repeats every 28 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 2 additional courses after achieving CR or up to a total of 6 courses. The first two cohorts of 3-6 patients each receive escalating doses of BMS-247550 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT).The third and fourth cohorts of 10 patients each receive escalating doses of BMS-247550 until the MTD is determined. The MTD is defined as the dose preceding that at which at least 3 of 10 patients experience DLT. Once the MTD is determined for the third and fourth cohorts, 15 additional patients are treated at the MTD. Patients are followed for 30 days.

Study Design

Study Type:
Interventional
Actual Enrollment :
45 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Study of Epothilone B Analog BMS 247550 in Combination With Carboplatin in Recurrent and/or Refractory Solid Tumors
Study Start Date :
Oct 1, 2001
Actual Primary Completion Date :
Feb 1, 2007

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (ixabepilone, carboplatin)

Patients receive BMS-247550 IV over 1 hour on days 1, 8, and 15 followed by carboplatin IV over 1 hour on day 1. Treatment repeats every 28 days for at least 2 courses in the absence of disease progression or unacceptable toxicity. Patients with a CR receive 2 additional courses after achieving CR or up to a total of 6 courses

Drug: ixabepilone
Given IV
Other Names:
  • BMS-247550
  • epothilone B lactam
  • Ixempra

    • Drug: carboplatin
    Given IV
    Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin

    • Other: laboratory biomarker analysis
    Correlative studies

    Other: pharmacological study
    Correlative studies
    Other Names:
  • pharmacological studies

    		•

    Outcome Measures

    Primary Outcome Measures

    1. MTD of ixabepilone defined as the first dosage tier below the MAD in which =< 1/6 patients experiences a DLT [28 days]

    Secondary Outcome Measures

    1. Pharmacokinetics of ixabepilone and carboplatin [Week 1]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Histologically or cytologically confirmed metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective

    • Measurable or evaluable disease

    • Lesion accessible for core or excisional biopsy if being treated at the maximum tolerated dose (MTD)

    • No biliary tract dilation if radiologically guided biopsy of the liver is planned

    • No requirement for core biopsy of lung lesion that is not pleural based

    • No requirement for laparotomy or thoracotomy solely for biopsy

    • No medical condition that would preclude biopsy

    • No known brain metastases

    • Performance status - ECOG 0-2

    • Performance status - ECOG 0-1 if being treated at the MTD

    • More than 3 months

    • Absolute neutrophil count at least 1,500/mm^3

    • Platelet count at least 100,000/mm^3

    • No prior bleeding disorder or unexplained bleeding if being treated at the MTD

    • Bilirubin no greater than 1.5 mg/dL

    • AST/ALT no greater than 2 times upper limit of normal (ULN) (5 times ULN if liver metastases present)

    • PT/PTT normal

    • Creatinine no greater than 1.5 times ULN

    • Creatinine clearance at least 60 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 other concurrent uncontrolled illness that would preclude study participation

    • No ongoing or active infection

    • No grade 2 or greater neuropathy (sensory or motor)

    • No prior severe allergic reaction attributable to compounds containing Cremophor EL or platinum agents

    • No psychiatric illness or social situation that would preclude study compliance

    • No medical condition that would preclude study if being treated at the MTD

    • At least 4 week since prior immunotherapy

    • At least 24 hours since prior growth factors

    • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

    • No more than 3 prior chemotherapy regimens

    • No prior epothilone agents

    • At least 1 week since prior hormonal therapy directed at malignancy

    • Concurrent hormone replacement therapy allowed

    • At least 4 weeks since prior wide-field radiotherapy involving 30% or more of bone marrow

    • See Disease Characteristics

    • At least 4 weeks since prior investigational agents

    • No prior or concurrent St. John's Wort

    • No concurrent combination anti-retroviral therapy for HIV-positive patients

    • No other concurrent investigational agents

    • No concurrent heparin or other anticoagulants if being treated at the MTD

    • No concurrent inhibitors of cytochrome P450 3AP (CYP3A4)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 H. Lee Moffitt Cancer Center and Research Institute Tampa Florida United States 33612

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Daniel Sullivan, H. Lee Moffitt Cancer Center and Research Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00028561
    Other Study ID Numbers:
    • NCI-2012-02726
    • 12657
    • CDR0000069105
    First Posted:
    Jan 27, 2003
    Last Update Posted:
    Jan 17, 2013
    Last Verified:
    Jan 1, 2013
    Additional relevant MeSH terms:
    Neoplasms
    Carboplatin
    Epothilone B
    Epothilones

    Study Results

    No Results Posted as of Jan 17, 2013