A Phase I Study of Epothilone B Analog BMS 247550 in Combination With Carboplatin in Recurrent and/or Refractory Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Study of Epothilone B Analog BMS 247550 in Combination With Carboplatin in Recurrent and/or Refractory Solid Tumors
OBJECTIVES:
I. Determine the maximum tolerated dose of BMS-247550 when given in combination with
carboplatin in patients with recurrent or refractory solid tumors.
II. Determine the dose-limiting toxicity and safety of this regimen in these patients.
III. Determine the plasma pharmacokinetics of this regimen in these patients. IV. Determine,
preliminarily, any antitumor activity of this regimen in these patients.
V. 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.
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)
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
MTD of ixabepilone defined as the first dosage tier below the MAD in which =< 1/6 patients experiences a DLT
Outcome Time Frame:
28 days
Safety Issue:
Yes
Principal Investigator
Daniel Sullivan
Investigator Role:
Principal Investigator
Investigator Affiliation:
H. Lee Moffitt Cancer Center and Research Institute
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02726
NCT ID:
NCT00028561
Start Date:
October 2001
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- Neoplasms
Name | Location |
|---|---|
| H. Lee Moffitt Cancer Center and Research Institute | Tampa, Florida 33612 |
