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Sodium Stibogluconate and Interferon Alfa-2b Followed By Cisplatin, Vinblastine, and Temozolomide in Treating Patients With Advanced Melanoma or Other Cancer
This study is not yet open for participant recruitment.
Verified by National Cancer Institute (NCI), May 2008
First Received: July 10, 2007   Last Updated: February 6, 2009   History of Changes
Sponsor: Case Comprehensive Cancer Center
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00498979
  Purpose

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 temozolomide, 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 temozolomide in treating patients with advanced melanoma or other cancer.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Melanoma (Skin)
Biological: recombinant interferon alfa-2b
Drug: cisplatin
Drug: sodium stibogluconate
Drug: temozolomide
Drug: vinblastine
Genetic: gene expression analysis
Other: immunoenzyme technique
Other: laboratory biomarker analysis
Other: pharmacological study
Phase I

Study Type: Interventional
Study Design: Treatment, Open Label
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Safety of the combination of sodium stibogluconate and interferon alfa-2b with chemotherapy [ Designated as safety issue: Yes ]
  • Activity of sodium stibogluconate in augmenting cytokine effects [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effects of sodium stibogluconate on interferon alfa-2b induced gene modulation and signal transduction pathways by measuring the serum soluble gene product [ Designated as safety issue: No ]
  • Effectiveness of sodium stibogluconate in inhibiting the protein tyrosine phosphatases SHP-1 and SHP-2 assayed from peripheral blood leukocytes [ Designated as safety issue: No ]
  • Pharmacokinetics of sodium stibogluconate in serum at escalating doses [ Designated as safety issue: No ]
  • Clinical response to the combination of sodium stibogluconate and interferon alfa-2b as priming for combination chemotherapy [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: May 2007
Estimated Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Detailed Description:

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)

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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00498979

Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Ernest C. Borden, MD The Cleveland Clinic
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000557420, CASE-3Y06
Study First Received: July 10, 2007
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00498979     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Anti-Infective Agents
Antiprotozoal Agents
Interferon Type I, Recombinant
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Vinblastine
Central Nervous System Neoplasms
Melanoma
Antiparasitic Agents
Neoplasms by Site
Antimony Sodium Gluconate
Cisplatin
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Nevi and Melanomas
Growth Inhibitors
Angiogenesis Modulating Agents
Alkylating Agents
Nervous System Neoplasms
Interferon-alpha
Neoplasms by Histologic Type
Antiplatyhelmintic Agents
Growth Substances
Mitosis Modulators
Nervous System Diseases
Interferons
Anthelmintics

ClinicalTrials.gov processed this record on February 08, 2010