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

Phase I Evaluation of Sodium Stibogluconate in Combination With Interferon α-2b for Solid Tumors, Lymphoma or Myeloma

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.

Study Overview

• Status: Terminated
• Conditions: Cancer
• Intervention / Treatment: Biological: recombinant interferon alfa-2b; Drug: sodium stibogluconate; Drug: SSG & interferon

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SSG & INF; 1 arm study: SSG & interferon	Biological: recombinant interferon alfa-2b; SSG x 5 week; Other Names: Sodium Stibocluconate; Drug: sodium stibogluconate; SSG & IFN; Drug: SSG & interferon; 1 arm study with SSG & interferon; Other Names: Sodium Stiboglucante

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Tolerance, safety, and maximum tolerated dose at 1 week after each course	3 years

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Ernest C. Borden, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: April 5, 2006
• First Submitted That Met QC Criteria: April 5, 2006
• First Posted (Estimate): April 6, 2006

Study Record Updates

• Last Update Posted (Actual): January 26, 2018
• Last Update Submitted That Met QC Criteria: January 24, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma; stage IV adult soft tissue sarcoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Antiprotozoal Agents; Antiparasitic Agents; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Interferons; Interferon-alpha; Interferon alpha-2; Antimony Sodium Gluconate
• Other Study ID Numbers: CASE-CCF-7059; P30CA043703 (U.S. NIH Grant/Contract); CASE-CCF-7509 (Other Identifier: IRB number); CASE-CCF-1062 (Other Identifier: IRB number); CASE 2Y06 (Other Identifier: IRB Number)