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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00659178
First received: April 10, 2008
Last updated: March 15, 2012
Last verified: March 2011
  Purpose

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.


Condition Intervention Phase
Primary Peritoneal Carcinoma
Epithelial Ovarian Carcinoma
Neoplasms, Ovarian
Fallopian Tube Cancer
Drug: SB-485232 (interleukin 18), pegylated liposomal doxorubicin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Safety and tolerability of SB-485232/Doxil combination therapy [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Biological activity of SB-485232/Doxil combination therapy [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters for SB-485232 and Doxil: AUC(0-t), Cmax, and Cmin [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
  • Pharmacodynamic biomarker responses [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
  • Immunogenicity (anti-SB-485232 and anti-PEG antibodies) [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
  • Anti-tumor activity (Radiographic tumor assessments and serum CA-125 levels) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: June 2008
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SB-485232 plus pegylated liposomal doxorubicin Drug: SB-485232 (interleukin 18), pegylated liposomal doxorubicin
SB-485232 (interleukin 18), pegylated liposomal doxorubicin
Other Names:
  • SB-485232 (interleukin 18)
  • pegylated liposomal doxorubicin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00659178

Locations
United States, California
GSK Investigational Site
Stanford, California, United States, 94305-5317
United States, Florida
GSK Investigational Site
Miami, Florida, United States, 33136
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00659178     History of Changes
Other Study ID Numbers: ILI108621
Study First Received: April 10, 2008
Last Updated: March 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
ovarian cancer
IL-18,
Doxil,
combination study,
pegylated liposomal doxorubicin,
immunotherapy,
cytokine,

Additional relevant MeSH terms:
Ovarian Neoplasms
Carcinoma
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms by Histologic Type
Fallopian Tube Diseases
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014