Phase I Evaluation of Sodium Stibogluconate in Combination With Interferon α-2b for Solid Tumors, Lymphoma or Myeloma
18 Years
N/A
Both
Cancer
Trial Information
Phase I Evaluation of Sodium Stibogluconate in Combination With Interferon α-2b for Solid Tumors, Lymphoma or Myeloma
OBJECTIVES:
Primary
- Confirm the tolerance, safety, and maximum tolerated dose of sodium stibogluconate
(SSG) in combination with interferon alfa-2b in patients with advanced solid tumors,
lymphoma, or myeloma.
Secondary
- Quantify the effect of SSG on interferon alfa-2b-induced gene modulation and signal
transduction pathways by measurement of the serum-soluble gene products β-2
microglobulin, immune serum globulin 15, and neopterin.
- Define the effectiveness of SSG in inhibiting the protein tyrosine phosphatases src
homology proteins (SHP)-1 and SHP-2 assayed from peripheral blood leukocytes of
patients receiving SSG in combination with interferon alfa-2b.
- Define pharmacokinetics of SSG in serum at escalating doses.
- Assess clinical response to the combination of SSG and interferon alfa-2b.
OUTLINE: This is an open-label, dose-escalation study of sodium stibogluconate (SSG).
Patients receive SSG IV over 15 minutes on days 1, 15-19, and 22-26 and interferon alfa-2b
subcutaneously daily on days 8-12 and 15-28. Treatment repeats every 6 weeks in the absence
of disease progression or unacceptable toxicity.
Cohorts of 6 patients receive escalating doses of SSG until the maximum tolerated dose (MTD)
is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients
experience dose-limiting toxicity.
PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed malignancy, including, but not limited to, any of the
following:
- Renal cell carcinoma
- Melanoma
- Kaposi's sarcoma
- Breast, prostate, colorectal, or lung adenocarcinoma
- Bone and soft tissue sarcomas
- Lymphoma
- Myeloma
- Tumors of neuroendocrine and endothelial cell origin
- Stage IV disease
- Refractory disease, resistant to established treatments, or no effective treatment
available
- Measurable or evaluable disease
- CNS metastases allowed if no prior definitive therapy within the past 3 months and no
glucocorticoids required
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Granulocyte count > 1,500/mm^3
- Platelet count > 100,000/mm^3
- Creatinine < 1.0 times upper limit of normal (ULN)
- Creatinine clearance ≥ 60 mL/min
- Bilirubin < 1.5 times ULN
- AST/ALT < 1.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment
- No history of any of the following:
- Atrial fibrillation, atrial flutter, or other serious arrhythmia (excluding
asymptomatic atrial and ventricular premature complexes)
- Congestive heart failure currently requiring treatment
- Angina pectoris
- Other severe cardiovascular disease (i.e., New York Heart Association class III
or IV heart disease)
- No baseline ECG abnormalities suggestive of cardiac conduction delay, i.e., 1° or
greater atrio-ventricular block and/or complete or incomplete (QRS > 120 ms) bundle
branch block, or repolarization abnormalities (i.e., QTc ≥ 0.48 sec)
- No systemic infections requiring antibiotics within the past 14 days
- No known hepatitis B surface antigen positivity
- Psychologically prepared to participate in study treatment
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 4 weeks since prior interferon (IFN) therapy and/or ≤ 400 million units of
IFN
- At least 3 weeks since prior major surgery
- At least 3 weeks since prior radiation therapy or chemotherapy
- No prior solid organ allografts or allogeneic bone marrow transplantation
- No concurrent daily glucocorticoids except for physiological replacement
- No other concurrent medications known to prolong QT interval
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Tolerance, safety, and maximum tolerated dose at 1 week after each course
Outcome Time Frame:
3 years
Safety Issue:
Yes
Principal Investigator
Ernest C. Borden, MD
Investigator Role:
Study Chair
Investigator Affiliation:
The Cleveland Clinic
Authority:
United States: Food and Drug Administration
Study ID:
CASE-CCF-7509
NCT ID:
NCT00311558
Start Date:
October 2005
Completion Date:
May 2012
Related Keywords:
- Cancer
- stage IV melanoma
- stage IV adult soft tissue sarcoma
- recurrent melanoma
- Lymphoma
Name | Location |
|---|---|
| Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
