Clinical trial NCT00311558: Sodium Stibogluconate and Interferon in Treating Patients With Advanced Solid Tumors, Lymphoma, or Myeloma
Official title: Phase I Evaluation of Sodium Stibogluconate in Combination With Interferon α-2b for Solid Tumors, Lymphoma or Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Cancer
Keywords: stage IV melanoma
stage IV adult soft tissue sarcoma
recurrent melanoma
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-04-06
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Tolerance, safety, and maximum tolerated dose at 1 week after each course
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Ernest C. Borden, MD
role: STUDY_CHAIR
References: