A Phase I, Dose Escalation Study to Assess the Safety & Biological Activity of Interleukin 18 (SB-485232) Administered by IV Infusion in Combination With Pegylated Liposomal Doxorubicin (Doxil) in Advanced Stage Epithelial Ovarian Cancer

GlaxoSmithKline1 site in 1 country15 target enrollmentJune 18, 2008

ConditionsNeoplasms, Ovarian

InterventionsSB-485232 (interleukin 18), pegylated liposomal doxorubicin

DrugsSB-485232 (interleukin 18), pegylated liposomal doxorubicin

Overview

Phase: Phase 1
Intervention: SB-485232 (interleukin 18), pegylated liposomal doxorubicin
Conditions: Neoplasms, Ovarian
Sponsor: GlaxoSmithKline
Enrollment: 15
Locations: 1
Primary Endpoint: Safety and tolerability of SB-485232/Doxil combination therapy
Status: Completed
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to identify a dose of SB-485232 which is safe, tolerable and biologically active when used in combination with pegylated liposomal doxorubicin (Doxil) in patients with epithelial ovarian cancer. This study will use a standard treatment regimen of pegylated liposomal doxorubicin (Doxil) in combination with rising doses of SB-485232. The dose selected from this study will be used in a future studies to evaluate the efficacy of this combination.

Registry

clinicaltrials.gov

Start Date

June 18, 2008

End Date

February 18, 2011

Last Updated

8 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Female, age ≥18 years of age;
•Histologically confirmed diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma;
•Candidate to receive pegylated liposomal doxorubicin for treatment of advanced stage ovarian cancer as per standard of care and in the opinion of the treating principal investigator;
•Measurable lesion(s) according to RECIST v1.0;
•ECOG performance status of 0, 1 or 2;
•Predicted life expectancy of ≥4 months
•No chemotherapy, immunotherapy, hormonal therapy, or biological therapy for cancer, radiotherapy, or surgical procedures (except for minor surgical procedures) within four weeks before beginning treatment with SB-485232 (six weeks for nitrosoureas and mitomycin C). Subjects must have recovered from toxicities (incurred as a result of previous therapy) sufficiently to be entered into a Phase I study;
•Disease-free period of at least five years from prior malignancies (except for curatively treated basal and squamous cell carcinomas of the skin and/or carcinoma of the cervix in situ);
•Left ventricular ejection fraction (LVEF) ≥50 % as determined by MUGA scan;
•A signed and dated written informed consent form is obtained from the subject;

Exclusion Criteria

•Significant cardiac, pulmonary, metabolic, renal, hepatic, gastrointestinal or autoimmune conditions that in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as participant in this trial;
•Any severe concurrent disease or condition, including significant active autoimmune diseases such as rheumatoid arthritis, which in the judgment of the principal investigator, would make the subject inappropriate for study participation;
•History of myocardial infarction, unstable angina, or acute coronary syndrome within the past six months;
•The subject has a history of hypersensitivity reactions to a conventional formulation of doxorubicin HCl or the components of pegylated liposomal doxorubicin;
•The subject has a history of receiving a total cumulative dosage of doxorubicin HCl exceeding the currently recommended limit of 550 mg/m\^2 or will exceed the 550 mg/m\^2 dosage limit during the course of the current study. A subject will also be excluded if they received a lower cumulative dosage of doxorubicin HCl (i.e., 400 mg/m\^2) and also had prior radiotherapy to the mediastinal area or concomitant therapy with other potentially cardiotoxic agents such as cyclophosphamide. Prior use of other anthracyclines or anthracenediones should be included in calculations of total cumulative doxorubicin HCl dosage;
•Women who are pregnant or are breast-feeding;
•Corrected QT interval (QTc) ≥480 msec (average of three measurements to be made at screening);
•The subject has diabetes mellitus with poor glycemic control;
•The subject has a history of human immunodeficiency virus (HIV) or other immunodeficiency disease;
•The subject has positive Hepatitis B surface antigen;

Arms & Interventions

SB-485232 plus pegylated liposomal doxorubicin

Subjects will receive one dose of pegylated liposomal doxorubicin on Day 1 plus two doses of SB-485232 on Day 3 and Day 9 in each cycle.

Intervention: SB-485232 (interleukin 18), pegylated liposomal doxorubicin

Outcomes

Primary Outcomes

Safety and tolerability of SB-485232/Doxil combination therapy

Time Frame: 16 weeks

Secondary Outcomes

Biological activity of SB-485232/Doxil combination therapy(16 weeks)
Pharmacokinetic parameters for SB-485232 and Doxil: AUC(0-t), Cmax, and Cmin(16 weeks)
Pharmacodynamic biomarker responses(16 weeks)
Immunogenicity (anti-SB-485232 and anti-PEG antibodies)(16 weeks)
Anti-tumor activity (Radiographic tumor assessments and serum CA-125 levels)(16 weeks)