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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00498979
First received: July 10, 2007
Last updated: January 11, 2012
Last verified: January 2012
  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 dacarbazine, 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 dacarbazine in treating patients with advanced melanoma or other cancer.


Condition Intervention Phase
Stage IV Melanoma
Biological: recombinant interferon alfa-2b
Drug: cisplatin
Drug: sodium stibogluconate
Drug: dacarbazine
Drug: vinblastine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Safety of the combination of sodium stibogluconate and interferon alfa-2b with chemotherapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

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 [ Time Frame: 2 years ] [ 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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Pharmacokinetics of sodium stibogluconate in serum at escalating doses [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Clinical response to the combination of sodium stibogluconate and interferon alfa-2b as priming for combination chemotherapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: May 2007
Study Completion Date: January 2012
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: recombinant interferon alfa-2b
recombinant interferon alfa-2b
Biological: recombinant interferon alfa-2b
recombinant interferon alfa-2b
Other Name: IFN 2b
Drug: cisplatin
recombinant interferon alfa-2b
Other Name: CDDP
Drug: sodium stibogluconate
sodium stibogluconate
Other Name: sodium stibogluconate
Drug: dacarbazine
dacarbazine
Other Name: DTIC
Drug: vinblastine
vinblastine
Other Name: VBL

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 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.

  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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Ohio
Cleveland Clinic Taussig Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Ernest C. Borden, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00498979     History of Changes
Other Study ID Numbers: CASE3Y06, P30CA043703
Study First Received: July 10, 2007
Last Updated: January 11, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:
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:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Interferon-alpha
Interferon Alfa-2a
Interferon Alfa-2b
Interferons
Reaferon
Antimony Sodium Gluconate
Cisplatin
Dacarbazine
Vinblastine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Schistosomicides
Antiplatyhelmintic Agents

ClinicalTrials.gov processed this record on July 26, 2014