Phase I Evaluation of Sodium Stibogluconate in Combination With Interferon α-2b Followed by Cisplatin, Vinblastine and Dacarbazine for Patients With Melanoma or Malignancies Potentially Responsive to SSG and/or Interferons
- To determine the safety of the combination of sodium stibogluconate and interferon
alfa-2b with chemotherapy.
- To confirm the activity of sodium stibogluconate in augmenting cytokine effects.
- To quantify the effects of sodium stibogluconate on interferon alfa-2b induced gene
modulation and signal transduction pathways by measuring the serum soluble gene
- To define the effectiveness of sodium stibogluconate in inhibiting the protein tyrosine
phosphatases SHP-1 and SHP-2 assayed from peripheral blood leukocytes of patients
receiving sodium stibogluconate in combination with interferon alfa-2b.
- To define the pharmacokinetics of sodium stibogluconate in serum at escalating doses.
- To assess clinical response to the combination of sodium stibogluconate and interferon
alfa-2b as priming for combination chemotherapy.
- Course 1: Patients receive sodium stibogluconate IV over 15 minutes on day 1 and days
15-18; interferon alfa-2b subcutaneously (SC) on days 8-12 and 15-18; cisplatin IV over
30-60 minutes and vinblastine IV on days 19 and 20; and dacarbazine. After a 2-week
rest period, patients proceed to course 2.
- Course 2 and all subsequent courses: Patients receive sodium stibogluconate IV over 15
minutes and interferon alfa-2b SC on days 1-4; cisplatin IV over 30-60 minutes and
vinblastine IV on days 5 and 6; dacarbazine. Courses repeat every 4 weeks in the
absence of disease progression or unacceptable toxicity.* NOTE: *Patients with stage IV
disease who have no evidence of disease [NED} receive only 4 courses of therapy.
Cohorts of 6 patients receive escalating doses of sodium stibogluconate until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which
dose-limiting toxicity occurs (i.e., no more than 1 patient at a given dose experiences
Patients undergo blood sample collection periodically for immunological and pharmacokinetic
studies. Samples are analyzed for serum soluble gene products and protein tyrosine
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety of the combination of sodium stibogluconate and interferon alfa-2b with chemotherapy
Ernest C. Borden, MD
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
United States: Food and Drug Administration
|Cleveland Clinic Taussig Institute, Case Comprehensive Cancer Center||Cleveland, Ohio 44195|