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Gynecol Oncol. 2017 Nov;147(2):283-290. doi: 10.1016/j.ygyno.2017.08.001. Epub 2017 Aug 10.

A phase I trial of intraperitoneal GEN-1, an IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer, administered with pegylated liposomal doxorubicin in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancers: An NRG Oncology/Gynecologic Oncology Group study.

Author information

1
Division of Gynecologic Oncology, Washington University School of Medicine and Siteman Cancer Center, St. Louis, MO, USA. Electronic address: thakerp@wudosis.wustl.edu.
2
NRG Oncology Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, NY, USA. Electronic address: bbrady@gogstats.org.
3
NRG Oncology Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, NY, USA. Electronic address: LankesH@NRGOncology.org.
4
Department of Gynecology, Roswell Park Cancer Institute, Buffalo, NY, USA. Electronic address: Kunle.Odunsi@RoswellPark.org.
5
Division of Gynecologic Oncology, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: wbradley@mcw.edu.
6
Division of Gynecologic Oncology, University of Oklahoma and Stephenson Cancer Center, Oklahoma City, OK, USA. Electronic address: kathleen-moore@ouhsc.edu.
7
University of New Mexico, Albuquerque, NM, USA. Electronic address: cmuller@salud.unm.edu.
8
Celsion Corporation, Lawrenceville, NJ, USA. Electronic address: KAnwer@celsion.com.
9
Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA, USA. Electronic address: russell.schilder@jefferson.edu.
10
Division of Gynecologic Oncology, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: ralvarez@uabmc.edu.
11
Department of Medicine and the UVA Cancer Center, University of Virginia, Charlottesville, VA, USA. Electronic address: fracasso@virginia.edu.

Abstract

OBJECTIVE:

The study's purpose was to assess safety and efficacy of escalating doses of weekly GEN-1 with pegylated liposomal doxorubicin (PLD) in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancers (EOC).

METHODS:

Patients had persistent or recurrent platinum-resistant EOC. The trial was a standard 3+3 phase I dose escalation design with patients receiving intravenous PLD 40mg/m2 (dose level 1 and 2) or 50mg/m2 (dose level 3) every 28days and intraperitoneal GEN-1 at 24mg/m2 (dose level 1) or 36mg/m2 (dose level 2 and 3) on days 1, 8, 15, and 22 of a 28day cycle. Cycles were repeated every 28days until disease progression. Patients were monitored for toxicity, clinical efficacy, and evidence of systemic and intraperitoneal immunologic effect.

RESULTS:

Sixteen evaluable patients received a median of 4cycles (range 1-8). No dose limiting toxicities were found. The adverse side effects were 4 grade 3 anemia, 2 grade 3 abdominal pain, 7 grade 3 neutropenia, and 2 grade 4 neutropenia. A clinical benefit of 57.1% (PR=21.4%; SD=35.7%) was found in the 14 patients with measurable disease. The highest number of partial responses (28.6%) and stable disease (57.1%) were found at dose level 3. The maximum tolerated dose was not reached. Increases in IL-12, IFN-γ, and TNF-α levels were found in peritoneal fluid following GEN-1 treatment.

CONCLUSIONS:

GEN-1 in combination with PLD has encouraging clinical benefit and biological activity in recurrent or persistent EOC and warrants further investigation with escalating doses of GEN-1.

KEYWORDS:

GEN-1; IL-12 plasmid; Pegylated liposomal doxorubicin; Primary peritoneal cancer

PMID:
28802766
PMCID:
PMC5704992
DOI:
10.1016/j.ygyno.2017.08.001
[Indexed for MEDLINE]
Free PMC Article

Publication type, MeSH terms, Substances, Grant support

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