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An Open-Labeled, Non-Randomized Phase I Study of Safingol Administered With Cisplatin in Patients With Advanced Solid Tumors


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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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 CenterNew York, New York  10021