Sodium Stibogluconate and Interferon in Treating Patients With Advanced Solid Tumors, Lymphoma, or Myeloma

NeuroTherapia, Inc.

Status and phase

Terminated

Phase 1

Conditions

Cancer

Treatments

Biological: recombinant interferon alfa-2b

Drug: SSG & interferon

Drug: sodium stibogluconate

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00311558

CASE-CCF-7059

CASE-CCF-7509 (Other Identifier)

P30CA043703 (U.S. NIH Grant/Contract)

CASE-CCF-1062 (Other Identifier)

CASE 2Y06 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Sodium stibogluconate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Interferon may interfere with the growth of cancer cells. Giving sodium stibogluconate together with interferon may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of sodium stibogluconate when given together with interferon in treating patients with advanced solid tumors, lymphoma, or myeloma.

Full description

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.

Enrollment

18 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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