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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
N/A
Not Enrolling
Both
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


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.

Inclusion 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

Type of Study:

Interventional

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:

Yes

Principal Investigator

Ernest C. Borden, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

CASE3Y06

NCT ID:

NCT00498979

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

Name

Location

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