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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Sodium stibogluconate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of melanoma and other cancers. Drugs used in chemotherapy, such as cisplatin, vinblastine, and dacarbazine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sodium stibogluconate and interferon alfa-2b together with combination chemotherapy may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of sodium stibogluconate when given together with interferon alfa-2b, cisplatin, vinblastine, and dacarbazine in treating patients with advanced melanoma or other cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE:
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 DLT).
Patients undergo blood sample collection periodically for immunological and pharmacokinetic studies. Samples are analyzed for serum soluble gene products and protein tyrosine phosphatase inhibition.](streamdown:incomplete-link)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| recombinant interferon alfa-2b | Experimental | recombinant interferon alfa-2b |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| recombinant interferon alfa-2b | Biological | recombinant interferon alfa-2b |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety of the combination of sodium stibogluconate and interferon alfa-2b with chemotherapy | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Effects of sodium stibogluconate on interferon alfa-2b induced gene modulation and signal transduction pathways by measuring the serum soluble gene product | 2 years | |
| Effectiveness of sodium stibogluconate in inhibiting the protein tyrosine phosphatases SHP-1 and SHP-2 assayed from peripheral blood leukocytes |
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DISEASE CHARACTERISTICS:
Histologically confirmed melanoma or other malignancies
Must be refractory or resistant to established treatments OR have metastatic disease for which no effective therapy has been established
Gliomas or controlled CNS metastasis allowed
Malignancy potentially responsive to sodium stibogluconate and/or interferon alfa-2b and combination chemotherapy
Patients must have measurable or evaluable disease
PATIENT CHARACTERISTICS:
Inclusion criteria:
Exclusion criteria:
Pregnant or lactating women and fertile women or men unless surgically sterile or using effective contraception
History of atrial fibrillation, flutter, or other serious arrhythmia (excluding asymptomatic atrial or ventricular premature complexes) in the past 24 months
History of congestive heart failure currently requiring treatment; angina pectoris; or other severe cardiovascular disease (i.e., New York Heart Association class III or IV heart disease)
Baseline ECG abnormalities suggestive of cardiac conduction delay (i.e., first degree or greater atrio-ventricular block and/or complete or incomplete [QRS > 120 ms] bundle branch block)
Baseline ECG abnormalities suggestive of repolarization abnormalities (i.e., QTc ≥ 0.48 sec)
Culture positive acute infections requiring antibiotics within the past 14 days
Known to be positive for HBsAg
Patients judged to not be psychologically prepared to understand informed consent or comply with an investigational study
PRIOR CONCURRENT THERAPY:
Inclusion criteria:
Exclusion criteria:
No prior treatment with interferon, sodium stibogluconate, cisplatin, vinblastine, or dacarbazine, except if given in an adjuvant setting
Patients with a prior history of solid organ allografts or allogeneic bone marrow transplant
Patients taking the following medications will not be eligible:
Use of daily glucocorticoids except for physiological replacement
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| Name | Affiliation | Role |
|---|---|---|
| Ernest C. Borden, MD | Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cleveland Clinic Taussig Institute, Case Comprehensive Cancer Center | Cleveland | Ohio | 44195 | United States |
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| cisplatin | Drug | recombinant interferon alfa-2b |
|
|
| sodium stibogluconate | Drug | sodium stibogluconate |
|
| dacarbazine | Drug | dacarbazine |
|
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| vinblastine | Drug | vinblastine |
|
|
| 2 years |
| Pharmacokinetics of sodium stibogluconate in serum at escalating doses | 2 years |
| Clinical response to the combination of sodium stibogluconate and interferon alfa-2b as priming for combination chemotherapy | 2 years |
| ID | Term |
|---|---|
| D008545 | Melanoma |
| D001254 | Astrocytoma |
| D005909 | Glioblastoma |
| D004806 | Ependymoma |
| D018315 | Glioma, Subependymal |
| D009837 | Oligodendroglioma |
| D005910 | Glioma |
| D001932 | Brain Neoplasms |
| D018316 | Gliosarcoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D018302 | Neoplasms, Neuroepithelial |
| D009375 | Neoplasms, Glandular and Epithelial |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D007438 | Introns |
| D002945 | Cisplatin |
| D000967 | Antimony Sodium Gluconate |
| D003606 | Dacarbazine |
| D014747 | Vinblastine |
| ID | Term |
|---|---|
| D021901 | DNA, Intergenic |
| D040481 | Genome Components |
| D016678 | Genome |
| D040342 | Genetic Structures |
| D055614 | Genetic Phenomena |
| D040461 | Gene Components |
| D005796 | Genes |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D009930 | Organic Chemicals |
| D005942 | Gluconates |
| D013400 | Sugar Acids |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D006880 | Hydroxy Acids |
| D002241 | Carbohydrates |
| D014226 | Triazenes |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
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