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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

Phase 1
18 Years
Not Enrolling
Stage IV Melanoma

Thank you

Trial Information

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
phosphatase inhibition.

Inclusion Criteria


- 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

- 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


- 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


- 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

- Monoamine oxidase inhibitors

- High-dose methadone

- Arsenic trioxide

- Dolasetron (Anzemet)

- Any herbal preparations

- Use of daily glucocorticoids except for physiological replacement

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety of the combination of sodium stibogluconate and interferon alfa-2b with chemotherapy

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Ernest C. Borden, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

May 2007

Completion Date:

January 2012

Related Keywords:

  • Stage IV Melanoma
  • stage IV melanoma
  • adult anaplastic astrocytoma
  • adult diffuse astrocytoma
  • adult glioblastoma
  • adult giant cell glioblastoma
  • adult pilocytic astrocytoma
  • adult brain stem glioma
  • adult anaplastic ependymoma
  • adult ependymoma
  • adult myxopapillary ependymoma
  • adult subependymoma
  • adult anaplastic oligodendroglioma
  • adult oligodendroglioma
  • mixed gliomas
  • recurrent adult brain tumor
  • recurrent melanoma
  • adult gliosarcoma
  • adult subependymal giant cell astrocytoma
  • adult pineal gland astrocytoma
  • Melanoma



Cleveland Clinic Taussig Institute, Case Comprehensive Cancer Center Cleveland, Ohio  44195