Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	MCC-12657 NCI-5306, NCT00028561

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.
4. Determine, preliminarily, any antitumor activity of this regimen in these patients.
5. Correlate the protein expression of survivin with the expression of other apoptotic regulators, the apoptotic index, and response in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy:

• At least 4 week since prior immunotherapy
• At least 24 hours since prior growth factors

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No more than 3 prior chemotherapy regimens
• No prior epothilone agents

Endocrine therapy:

• At least 1 week since prior hormonal therapy directed at malignancy
• Concurrent hormone replacement therapy allowed

Radiotherapy:

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

Surgery:

• See Disease Characteristics

Other:

• 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)

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2
• ECOG 0-1 if being treated at the MTD

Life expectancy:

• More than 3 months

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• No prior bleeding disorder or unexplained bleeding if being treated at the MTD

Hepatic:

• 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

Renal:

• Creatinine no greater than 1.5 times ULN

  OR

• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• 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

Expected Enrollment

Approximately 18-45 patients will be accrued for this study within 6-15 months.

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.

Trial Contact Information

Trial Lead Organizations

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Daniel Sullivan, MD, Protocol chair		Ph: 813-979-3878; 888-663-3488

Registry Information
Official Title		A Phase I Study of Epothilone B Analog BMS 247550 in Combination with Carboplatin in Recurrent and/or Refractory Solid Tumors
Trial Start Date		2002-01-28
Registered in ClinicalTrials.gov		NCT00028561
Date Submitted to PDQ		2001-10-31
Information Last Verified		2004-04-13
NCI Grant/Contract Number		CA76292

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