Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Sodium Stibogluconate and Interferon alfa-2b Followed By Cisplatin, Vinblastine, and Temozolomide in Treating Patients With Advanced Melanoma or Other Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Biomarker/Laboratory analysis, Treatment	Approved-not yet active	18 and over	NCI	CASE-3Y06 Case 3Y06, NCT00498979

Objectives

Primary

1. To determine the safety of the combination of sodium stibogluconate and interferon alfa-2b with chemotherapy.
2. To confirm the activity of sodium stibogluconate in augmenting cytokine effects.

Secondary

1. 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.
2. 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.
3. To define the pharmacokinetics of sodium stibogluconate in serum at escalating doses.
4. To assess clinical response to the combination of sodium stibogluconate and interferon alfa-2b as priming for combination chemotherapy.

Entry Criteria

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)

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 temozolomide, 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

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

Expected Enrollment

Outcomes

Safety of the combination of sodium stibogluconate and interferon alfa-2b with chemotherapy
Activity of sodium stibogluconate in augmenting cytokine effects

Effects of sodium stibogluconate on interferon alfa-2b induced gene modulation and signal transduction pathways by measuring the serum soluble gene product
Effectiveness of sodium stibogluconate in inhibiting the protein tyrosine phosphatases SHP-1 and SHP-2 assayed from peripheral blood leukocytes
Pharmacokinetics of sodium stibogluconate in serum at escalating doses
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 oral temozolomide on days 19-22. 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; and oral temozolomide on days 5-8. 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.

Trial Contact Information

Trial Lead Organizations

Case Comprehensive Cancer Center

Ernest Borden, MD, Principal investigator		Ph: 216-444-8183; 800-862-7798 Email: bordene@ccf.org

Registry Information
Official Title		Phase I Evaluation of Sodium Stibogluconate in Combination With Interferon α-2b Followed by Cisplatin, Vinblastine and Temozolomide for Patients With Melanoma or Malignancies Potentially Responsive to SSG and/or Interferons
Trial Start Date		2007-05-29
Trial Completion Date		2009-02-02 (estimated)
Registered in ClinicalTrials.gov		NCT00498979
Date Submitted to PDQ		2007-06-21
Information Last Verified		2008-05-24
NCI Grant/Contract Number		CA115494-01A1, CA43703