Dose-Escalating Study Of SB-485232 Administered Intravenously Every 28 Days To Adults With Solid Tumors Or Lymphomas

A Phase I, Dose-Escalation Study to Assess the Safety and Pharmacokinetics of SB- 485232 Administered as Five Daily Intravenous Infusions Repeated Every 28 Days in Adult Patients With Solid Tumors and Lymphomas

SB-485232 will be administered as five daily intravenous (IV) infusions repeated every 28 days in adult subjects with advanced solid tumors or lymphomas. Subjects may receive up to 6 cycles of treatment unless progressive disease or unacceptable toxicity is noted. Three dose levels of drug will be investigated. Safety evaluations, including blood sampling for various laboratory tests, will be conducted. Additional blood samples will also be taken to measure the amount of drug in the body at specific times.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Solid Tumor Cancer
• Intervention / Treatment: Drug: SB-485232

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • GSK Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • GSK Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213-2584
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

• Histopathological confirmation of cancer limited to a solid tumor malignancy or follicular lymphoma.
• Advanced or metastatic disease.
• Measurable disease.
• Females of child-bearing potential must use adequate birth control.
• Karnofsky Performance Status of 70% or greater.
• Predicted life expectancy of at least 12 weeks in the estimation of the physician conducting the study (Principal Investigator).
• Adequate laboratory results.
• Subjects with history of coronary artery disease must have a stress test without clinically significant abnormalities.
• Subjects with a history of congestive heart failure, myocardial infarction or prior anthracycline chemotherapy, must have a MUGA (Multiple Gated Acquisition) scan which demonstrates a left ventricular ejection fraction equal to or greater than 40%.
• Signed informed consent form

Exclusion Criteria:

• Female subject is pregnant or nursing (lactating).
• Active, chronic or uncontrolled infections requiring systemic antibiotic therapy.
• Serious medical or psychiatric disorder that would interfere with the subject''s safety or ability to sign the informed consent.
• Leptomeningeal disease or evidence of prior or current metastatic brain disease.
• Receiving concurrent chemotherapy, immunotherapy, radiotherapy, corticosteroid therapy, or investigational therapy.
• Received chemotherapy, radiotherapy, immunotherapy, hormonal therapy or biological therapy for cancer or underwent a surgical procedure (except for minor surgical procedures) within 4 weeks before beginning treatment with SB-485232 (6 weeks in case of nitrosureas or mitomycin C).
• Exposed to an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of SB-485232.
• Severe concurrent disease or condition, including clinically significant autoimmune disease, which in the judgement of the physician conducting the study (the principal investigator) would render the patient inappropriate for study participation.
• History of ventricular arrhythmias requiring drug or device therapy.
• An unresolved or unstable, serious toxicity from prior administration of another investigational product.
• Psychological, familial, sociological, or geographical limitations that do not permit compliance with this protocol.
• Received prior SB-485232 therapy.
• Poor venous access.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluation of adverse events and changes in laboratory values. The potential dose is a dose regimen with no more than 2 out of 6 patients experiencing a dose-limiting toxicity.	6 Months

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluation for the presence of anti-SB-485232 antibodies, IL-18 neutralizing activity, and clinical sequelae. Pharmacokinetic endpoints are AUC, Cmax, Cmin, CL,Vss, and t1/2. Flow cytometry data. Assessments of disease.	6 Months

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: April 1, 2004

Study Registration Dates

• First Submitted: June 16, 2004
• First Submitted That Met QC Criteria: June 17, 2004
• First Posted (Estimate): June 18, 2004

Study Record Updates

• Last Update Posted (Estimate): October 13, 2008
• Last Update Submitted That Met QC Criteria: October 9, 2008
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: oncology; pharmacokinetics; Advanced cancer; Phase 1; IL-18; repeat dosing
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: 485232/003; 003 (NuSkin International)