Combination Study Of SB-485232 (Interleukin 18) And Doxil For Advanced Stage Epithelial Ovarian Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms, Ovarian
• Intervention / Treatment: Drug: SB-485232 (interleukin 18), pegylated liposomal doxorubicin

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305-5317
      • GSK Investigational Site
  • Florida
    • Miami, Florida, United States, 33136
      • GSK Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • 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: Female

Description

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 investigator;
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 screening);
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 therapy;
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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: SB-485232 (interleukin 18), pegylated liposomal doxorubicin; SB-485232 (interleukin 18), pegylated liposomal doxorubicin; Other Names: pegylated liposomal doxorubicin; SB-485232 (interleukin 18)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of SB-485232/Doxil combination therapy	16 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2008
• Primary Completion (Actual): February 18, 2011
• Study Completion (Actual): February 18, 2011

Study Registration Dates

• First Submitted: April 10, 2008
• First Submitted That Met QC Criteria: April 10, 2008
• First Posted (Estimate): April 16, 2008

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: ovarian cancer; immunotherapy,; Doxil,; pegylated liposomal doxorubicin,; IL-18,; combination study,; cytokine,
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: ILI108621

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Statistical Analysis Plan
   Information identifier: ILI108621
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: ILI108621
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: ILI108621
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: ILI108621
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: ILI108621
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: ILI108621
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: ILI108621
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register