Sodium Stibogluconate and Interferon in Treating Patients With Advanced Solid Tumors, Lymphoma, or Myeloma

Study Overview
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Brief Summary
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RATIONALE: Sodium stibogluconate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Interferon may interfere with the growth of cancer cells. Giving sodium stibogluconate together with interferon may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of sodium stibogluconate when given together with interferon in treating patients with advanced solid tumors, lymphoma, or myeloma.

Detailed Description
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OBJECTIVES: Primary Confirm the tolerance, safety, and maximum tolerated dose of sodium stibogluconate (SSG) in combination with interferon alfa-2b in patients with advanced solid tumors, lymphoma, or myeloma. Secondary Quantify the effect of SSG on interferon alfa-2b-induced gene modulation and signal transduction pathways by measurement of the serum-soluble gene products β-2 microglobulin, immune serum globulin 15, and neopterin. Define the effectiveness of SSG in inhibiting the protein tyrosine phosphatases src homology proteins (SHP)-1 and SHP-2 assayed from peripheral blood leukocytes of patients receiving SSG in combination with interferon alfa-2b. Define pharmacokinetics of SSG in serum at escalating doses. Assess clinical response to the combination of SSG and interferon alfa-2b. OUTLINE: This is an open-label, dose-escalation study of sodium stibogluconate (SSG). Patients receive SSG IV over 15 minutes on days 1, 15-19, and 22-26 and interferon alfa-2b subcutaneously daily on days 8-12 and 15-28. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 6 patients receive escalating doses of SSG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Official Title
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Phase I Evaluation of Sodium Stibogluconate in Combination With Interferon α-2b for Solid Tumors, Lymphoma or Myeloma

Conditions
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Cancer

Intervention / Treatment
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* Biological: recombinant interferon alfa-2b
* Drug: sodium stibogluconate
* Drug: SSG & interferon


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed malignancy, including, but not limited to, any of the following: Renal cell carcinoma Melanoma Kaposi's sarcoma Breast, prostate, colorectal, or lung adenocarcinoma Bone and soft tissue sarcomas Lymphoma Myeloma Tumors of neuroendocrine and endothelial cell origin Stage IV disease Refractory disease, resistant to established treatments, or no effective treatment available Measurable or evaluable disease CNS metastases allowed if no prior definitive therapy within the past 3 months and no glucocorticoids required PATIENT CHARACTERISTICS: ECOG performance status 0-1 Granulocyte count > 1,500/mm^3 Platelet count > 100,000/mm^3 Creatinine < 1.0 times upper limit of normal (ULN) Creatinine clearance ≥ 60 mL/min Bilirubin < 1.5 times ULN AST/ALT < 1.5 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after completion of study treatment No history of any of the following: Atrial fibrillation, atrial flutter, or other serious arrhythmia (excluding asymptomatic atrial and ventricular premature complexes) Congestive heart failure currently requiring treatment Angina pectoris Other severe cardiovascular disease (i.e., New York Heart Association class III or IV heart disease) No baseline ECG abnormalities suggestive of cardiac conduction delay, i.e., 1° or greater atrio-ventricular block and/or complete or incomplete (QRS > 120 ms) bundle branch block, or repolarization abnormalities (i.e., QTc ≥ 0.48 sec) No systemic infections requiring antibiotics within the past 14 days No known hepatitis B surface antigen positivity Psychologically prepared to participate in study treatment PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 4 weeks since prior interferon (IFN) therapy and/or ≤ 400 million units of IFN At least 3 weeks since prior major surgery At least 3 weeks since prior radiation therapy or chemotherapy No prior solid organ allografts or allogeneic bone marrow transplantation No concurrent daily glucocorticoids except for physiological replacement No other concurrent medications known to prolong QT interval

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SSG & INF<br>1 arm study: SSG & interferon | Biological: recombinant interferon alfa-2b<br>* SSG x 5 week<br>* Other names: Sodium Stibocluconate;Drug: sodium stibogluconate<br>* SSG & IFN<br>Drug: SSG & interferon<br>* 1 arm study with SSG & interferon<br>* Other names: Sodium Stiboglucante;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance, safety, and maximum tolerated dose at 1 week after each course |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV melanoma, stage IV adult soft tissue sarcoma, recurrent melanoma