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

March 21, 2013 updated by: Memorial Sloan Kettering Cancer Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

43

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Safingol and Cisplatin

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
Drug: safingol

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Gary K. Schwartz, MD, Memorial Sloan Kettering Cancer Center
  • Principal Investigator: Archie N. Tse, MD, PhD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2004

Primary Completion (Actual)

February 1, 2009

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

June 10, 2004

First Submitted That Met QC Criteria

June 10, 2004

First Posted (Estimate)

June 11, 2004

Study Record Updates

Last Update Posted (Estimate)

March 22, 2013

Last Update Submitted That Met QC Criteria

March 21, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 04-002
  • MSKCC-04002

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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