Sodium Stibogluconate and IFNa-2b Followed By CDDP, VLB and DTIC Treating Pts.With Advanced Melanoma or Other Cancers

OBJECTIVES:

Primary

• 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.

Secondary

• To quantify the effects of sodium stibogluconate on interferon alfa-2b induced gene modulation and signal transduction pathways by measuring the serum soluble gene products.
• 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.

OUTLINE:

• 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 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.

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

• A CT scan or MRI must confirm stable brain metastases within 28 days of study entry
• Patients with primary CNS malignancies refractory to other therapies are eligible
• Malignancy potentially responsive to sodium stibogluconate and/or interferon alfa-2b and combination chemotherapy
• Patients must have measurable or evaluable disease

• Evaluable disease can include clinically or radiographically nonmeasurable tumor, specific tumor markers, or stage IV patients with no evidence of disease (NED)

PATIENT CHARACTERISTICS:

• Inclusion criteria:

• ECOG performance status 0-2
• Granulocytes > 1,500/μl
• Platelets > 100,000/μl
• Creatinine < 1.5 x upper limit of normal (ULN)
• Bilirubin < 1.5 x ULN
• AST and ALT < 1.5 x ULN (unless due to hepatic metastases)
• Potassium ≤ 5.0 mmol/L
• Magnesium ≤ 2.4 mg/dL
• Creatinine clearance ≥ 60 cc/min
• Ejection fraction ≥ 50%
• Exclusion criteria:

• Pregnant or lactating women and fertile women or men unless surgically sterile or using effective contraception

• All female patients of childbearing potential or less than 1 year postmenopausal must have a negative β-HCG pregnancy test at baseline and practice a medically acceptable method of birth control (i.e., oral contraceptives for at least 3 months, implantation of an intrauterine device for at least 2 months, or barrier methods [e.g., vaginal diaphragm, vaginal sponge, or condom with spermicidal jelly]) during and for 3 months after study initiation
• 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

• Patients on long term suppressive antibiotic therapies are eligible
• 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:

• Prior interferon therapy is allowed if administered ≥ 4 months ago
• At least 3 weeks since prior major surgery, radiation therapy, or chemotherapy
• 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:

• Amiodarone (Cordarone)
• Disopyramide (Norpace)
• Dofetilide (Tikosyn)
• Procainamide (Procanbid or Pronestyl)
• Quinidine (Quinaglute)
• Sotalol (Betapace)
• Erythromycin
• Azithromycin (Z-pack)
• Clarithromycin (Biaxin)
• Pentamidine (Pentacarinat)
• Trimethoprim-sulfamethoxazole (Bactrim)
• Bepridil (Vascor)
• Phenothiazines (e.g., prochlorperazine [Compazine], promethazine [Phenergan], or chlorpromazine [Thorazine])
• Butyrophenones (e.g., Haloperidol [Haldol])
• Risperidone (Risperdal)
• Any other antipsychotic medication
• Tricyclic or tetracyclic antidepressants (e.g., imipramine [Tofranil], amitriptyline [Elavil], desipramine [Norpramin], or nortriptyline [Pamelor])
• Monoamine oxidase inhibitors
• High-dose methadone
• Arsenic trioxide
• Dolasetron (Anzemet)
• Any herbal preparations
• Use of daily glucocorticoids except for physiological replacement