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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

Phase 1
18 Years
Not Enrolling
Primary Peritoneal Carcinoma, Epithelial Ovarian Carcinoma, Neoplasms, Ovarian, Fallopian Tube Cancer

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Trial Information

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

Inclusion Criteria:

1. Female, age ≥18 years of age;

2. Histologically confirmed diagnosis of epithelial ovarian, fallopian tube, or primary
peritoneal carcinoma;

3. 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

4. Measurable lesion(s) according to RECIST v1.0;

5. ECOG performance status of 0, 1 or 2;

6. Predicted life expectancy of ≥4 months

7. 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;

8. 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);

9. Left ventricular ejection fraction (LVEF) ≥50 % as determined by MUGA scan;

10. A signed and dated written informed consent form is obtained from the subject;

11. The subject is able to understand and comply with protocol requirements, timetables,
instructions and protocol-stated restrictions;

12. The subject is likely to maintain good venous blood access for PK and PD sampling
throughout the study;

13. A female is eligible to enter and participate in the study if she is of:
non-childbearing potential (i.e., physiologically incapable of becoming pregnant) or,
childbearing potential, has a negative serum pregnancy test at the screening visit,
and agrees to one of several GSK acceptable contraceptive methods;

14. Adequate organ function defined as: ANC ≥1.5 x 10^9/L; hemoglobin ≥9 g/dL (after
transfusion if needed); platelets ≥75 x 10^9/L.

Exclusion Criteria:

1. 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;

2. 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;

3. History of myocardial infarction, unstable angina, or acute coronary syndrome within
the past six months;

4. The subject has a history of hypersensitivity reactions to a conventional formulation
of doxorubicin HCl or the components of pegylated liposomal doxorubicin;

5. 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;

6. Women who are pregnant or are breast-feeding;

7. Corrected QT interval (QTc) ≥480 msec (average of three measurements to be made at

8. The subject has diabetes mellitus with poor glycemic control;

9. The subject has a history of human immunodeficiency virus (HIV) or other
immunodeficiency disease;

10. The subject has positive Hepatitis B surface antigen;

11. The subject has a history of a severe infusion-related reaction following treatment
with pegylated liposomal doxorubicin as described in the protocol;

12. The subject has an acute infection or severe or uncontrolled infections requiring
systemic antibiotic therapy;

13. Any serious medical or psychiatric disorder that would interfere with subject safety
or informed consent;

14. Psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol;

15. Known leptomeningeal disease or evidence of prior or current metastatic brain
disease. Routine screening with central nervous system (CNS) imaging studies (CT or
MRI) is required only if clinically indicated;

16. Receiving concurrent chemotherapy, immunotherapy, radiotherapy, or investigational

17. Oral corticosteroids within 14 days of study entry;

18. History of ventricular arrhythmias requiring drug or device therapy;

19. Any investigational drug within 30 days or five half-lives (whichever is longer)
preceding the first dose of SB-485232;

20. The subject has active signs of a bowel obstruction.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and tolerability of SB-485232/Doxil combination therapy

Outcome Time Frame:

16 weeks

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

June 2008

Completion Date:

February 2011

Related Keywords:

  • Primary Peritoneal Carcinoma
  • Epithelial Ovarian Carcinoma
  • Neoplasms, Ovarian
  • Fallopian Tube Cancer
  • ovarian cancer
  • IL-18,
  • Doxil,
  • combination study,
  • pegylated liposomal doxorubicin,
  • immunotherapy,
  • cytokine,
  • Neoplasms
  • Carcinoma
  • Ovarian Neoplasms
  • Neoplasms, Glandular and Epithelial
  • Fallopian Tube Neoplasms



GSK Investigational Site Bakersfield, California  93309
GSK Investigational Site Gainesville, Florida  32610
GSK Investigational Site Pittsburgh, Pennsylvania  15213