An Open-Labeled, Non-Randomized Phase I Study of Safingol Administered With Cisplatin in Patients With Advanced Solid Tumors
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
An Open-Labeled, Non-Randomized Phase I Study of Safingol Administered With Cisplatin in Patients With Advanced Solid Tumors
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) of safingol when administered with cisplatin
in patients with locally advanced or metastatic solid tumors.
Secondary
- Determine the toxic effects of this regimen in these patients.
- Determine the clinical pharmacokinetics of this regimen in these patients.
- Determine, preliminarily, the therapeutic activity of this regimen in these patients.
- Determine a safe dose (i.e., near the MTD) for phase II evaluation of this regimen in
these patients.
- Determine, preliminarily, the role of ceramide and S1P, relative to response and
apoptosis, in patients treated with this regimen.
OUTLINE: This is an open-label, non-randomized, dose-escalation study of safingol.
Patients receive safingol IV over 1 hour and cisplatin IV over 1 hour on day 1. Courses
repeat every 21 days* in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients receive safingol on days 1 and 8 and cisplatin on day 8 for course 1 only;
course 1 is 28 days in duration.
Cohorts of 3-6 patients receive escalating doses of safingol until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 additional
patients are treated at that dose level.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed solid tumor
- Locally advanced or metastatic disease
- Refractory to standard therapy OR not amenable to standard therapy
- No known CNS metastasis or CNS primary
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- Karnofsky 70-100%
Life expectancy
- At least 12 weeks
Hematopoietic
- Neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- WBC count ≥ 3,500/mm^3
- Hemoglobin ≥ 9.5 g/dL
- Haptoglobin ≥ 30 mg/dL
- No concurrent hemolysis or history of non-drug-induced hemolysis (e.g.,
spherocytosis)
Hepatic
- AST and ALT ≤ 2.5 times upper limit of normal
- Bilirubin ≤ 1.5 mg/dL
- PT and PTT normal
Renal
- Creatinine ≤ 1.5 mg/dL
Cardiovascular
- No cardiac arrhythmias
- No congestive heart failure
- No myocardial infarction within the past 6 months
Other
- Not pregnant
- Negative pregnancy test
- No nursing during and for at least 2 months after study participation
- Fertile patients must use effective contraception during and for at least 2 months
after study participation
- HIV negative
- No mental incapacity that would preclude giving informed consent
- No moderate-to-severe high-frequency hearing loss
- No persistent severe (grade 2) drug-induced peripheral neuropathy
- No known allergy to cisplatin or any other platinum-containing compound
- No serious or uncontrolled infection
- No other medical condition or reason that would preclude study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 4 weeks since prior immunotherapy
Chemotherapy
- Prior cisplatin allowed
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin)
Endocrine therapy
- Not specified
Radiotherapy
- At least 4 weeks since prior radiotherapy
Surgery
- Not specified
Other
- Recovered from all prior therapy
- No concurrent vitamins, antioxidants, herbal preparations, or supplements
- Concurrent single tablet multivitamin allowed
- No other concurrent investigational medications
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Recommended phase II dose as assessed by NCI toxicity scale during 3-4 weeks of treatment
Outcome Time Frame:
2 years
Safety Issue:
Yes
Principal Investigator
Gary K. Schwartz, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
04-002
NCT ID:
NCT00084812
Start Date:
March 2004
Completion Date:
February 2009
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
