EGEN-001 and Pegylated Liposomal Doxorubicin Hydrochloride in Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer
RATIONALE: Biological therapies, such as EGEN-001, may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving EGEN-001 together with pegylated liposomal doxorubicin hydrochloride may kill more tumor cells.
PURPOSE: This phase I trial studies the side effects and the best dose of giving EGEN-001 together with pegylated liposomal doxorubicin hydrochloride in treating patients with persistent or recurrent ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.
Fallopian Tube Cancer
Primary Peritoneal Cavity Cancer
Drug: pegylated liposomal doxorubicin hydrochloride
Genetic: RNA analysis
Other: laboratory biomarker analysis
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Intraperitoneal EGEN-001 (IL-12 Plasmid Formulated With PEG-PEI-Cholesterol Lipopolymer) (IND #12,484) Administered in Combination With Pegylated Liposomal Doxorubicin (PLD, Doxil (NSC #712227 or Lipodox) in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer|
- First course DLTs [ Time Frame: Cycle 1 ] [ Designated as safety issue: Yes ]
- The grade of toxicity as assessed by CTCAE v 4.0 [ Time Frame: Each cycle ] [ Designated as safety issue: Yes ]
- Objective tumor response (complete and partial response) [ Time Frame: Every 2 cycles ] [ Designated as safety issue: No ]
|Study Start Date:||September 2012|
|Estimated Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
EGEN-001 administered IP Day 1,8,15,22 of 28-day cycle
|Biological: EGEN-001 Drug: pegylated liposomal doxorubicin hydrochloride Genetic: RNA analysis Other: laboratory biomarker analysis|
- To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of EGEN-001 when administered in combination with pegylated liposomal doxorubicin hydrochloride (Doxil) and the associated DLTs based on adverse events that occur in cycle 1 for this combination in women with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer.
- To examine the tolerability of the combination at the MTD of EGEN-001 assessed in combination with Doxil.
- To determine recommended phase II dose (RP2D) of EGEN-001 in combination with Doxil.
- To estimate the objective response rate (complete and partial) in patients with measurable disease.
- Determine the levels and time course of interleukin-12 (IL-12), interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) following EGEN-001 treatment. (Exploratory)
- Assess the effect of EGEN-001 treatment on the nature of the cellular immune responses by measuring cell-specific ribonucleic acid (RNA) transcripts. (Exploratory)
OUTLINE: This is a multicenter, dose-escalation study of EGEN-001.
Patients receive pegylated liposomal doxorubicin hydrochloride intravenously (IV) over 60 minutes on day 1 and EGEN-001 intraperitoneally (IP) over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo peripheral blood and peritoneal fluid collection at baseline and after treatment for analysis of cytokines, including IL-12, IFN-γ, TNF-α, and VEGF, and RNA analysis.
After completion of study treatment, patients are followed up every 3 months for up to 1 year.
|United States, Missouri|
|Washington University School of Medicine||Recruiting|
|Saint Louis, Missouri, United States, 63110|
|Contact: David G. Mutch 800-600-3606 email@example.com|
|Principal Investigator: David G. Mutch|
|United States, Ohio|
|Case Western Reserve University||Recruiting|
|Cleveland, Ohio, United States, 44106|
|Contact: Steven E. Waggoner 800-641-2422|
|Principal Investigator: Steven E. Waggoner|
|United States, Oklahoma|
|University of Oklahoma Health Sciences Center||Recruiting|
|Oklahoma City, Oklahoma, United States, 73104|
|Contact: Robert S. Mannel 405-271-4272 firstname.lastname@example.org|
|Principal Investigator: Robert S. Mannel|
|Principal Investigator:||Premal H. Thaker, MD||Washington University School of Medicine|