Clinical Trial Finder

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

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.

Arms

Experimental: recombinant interferon alfa-2b

recombinant interferon alfa-2b

Interventions

Biological: - recombinant interferon alfa-2b

recombinant interferon alfa-2b

Drug: - cisplatin

recombinant interferon alfa-2b

Drug: - sodium stibogluconate

sodium stibogluconate

Drug: - dacarbazine

dacarbazine

Drug: - vinblastine

vinblastine