Faculty Collaboration Database

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. Gynecol Oncol 2017 Nov;147(2):283-290

Date

08/15/2017

Pubmed ID

28802766

Pubmed Central ID

PMC5704992

DOI

10.1016/j.ygyno.2017.08.001

Scopus ID

2-s2.0-85028062345 (requires institutional sign-in at Scopus site)   52 Citations

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.

Author List

Thaker PH, Brady WE, Lankes HA, Odunsi K, Bradley WH, Moore KN, Muller CY, Anwer K, Schilder RJ, Alvarez RD, Fracasso PM

Author

William H. Bradley MD Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Antibiotics, Antineoplastic
Disease-Free Survival
Dose-Response Relationship, Drug
Doxorubicin
Fallopian Tube Neoplasms
Female
Genetic Therapy
Humans
Interleukin-12
Middle Aged
Neoplasm Recurrence, Local
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Peritoneal Neoplasms
Plasmids
Polyethylene Glycols
Polyethyleneimine