Safingol and Cisplatin in Treating Patients With Locally Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Safingol may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by stopping blood flow to the tumor. PURPOSE: This phase I trial is studying the side effects and best dose of safingol when given with cisplatin in treating patients with locally advanced or metastatic solid tumors.

Detailed Description
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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.

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

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: cisplatin
* Drug: safingol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Safingol and Cisplatin<br>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. | Drug: cisplatin<br> <br> Drug: safingol<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended phase II dose as assessed by NCI toxicity scale during 3-4 weeks of treatment |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response as assessed by RECIST criteria during 3-6 weeks of treatment |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific