A phase II trial of intraperitoneal EGEN-001, an IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer: a gynecologic oncology group study.
OBJECTIVE
The purpose of this phase II trial was to evaluate the toxicity and antitumor activity of EGEN-001 in platinum resistant recurrent ovarian cancer.


METHODS
Eligible patients had weekly IP infusion of EGEN-001 at a dose of 24mg/m(2). Toxicity and antitumor activity were evaluated using CTCAE and RESIST criteria, respectively. Co-primary endpoints were tumor response and survival without progression (PFS) for at least 6months. Survival without progression before going onto a subsequent therapy (EFS) for at least six months was also considered.


RESULTS
A total of 58 EGEN-001 cycles were administered to 20/22 enrolled patients (median 2cycles, range 1-9). The most frequently associated adverse events related specifically to EGEN-001 treatment were grade 1/2 fatigue, fever, chills, abdominal pain, nausea, vomiting, anemia, thrombocytopenia, and leukopenia. Three of 20 EGEN-001 treated patients evaluable for toxicity elected to withdraw from the study motivated in part by grade 1 treatment related toxicities. There were no patients with partial or complete response (0%; 90% CI 0-10.9%). Seven (35%) of 16 patients evaluable for response had stable disease, and 9 (45%) had progressive disease. Six (30%) patients had a PFS of greater than six months, although three had gone off study and onto other therapies before six months. The estimated six-month EFS was 15%. The median PFS and OS were 2.89 and 9.17months, respectively.


CONCLUSIONS
EGEN-001 at the dose and schedule evaluated was associated with some but limited activity and was seemingly less tolerated in platinum resistant recurrent ovarian cancer patients.
Dept. of OB/GYN, University of Alabama School of Medicine, Birmingham, AL 35233-7333, USA. Electronic address: rdalvarez@uab.edu.
Ronald D
RD
Alvarez
Gynecologic Oncology Group Statistical & Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Michael W
MW
Sill
Dept. of OB/GYN, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO 80045, USA.
Susan A
SA
Davidson
Dept. of OB/GYN, University of New Mexico Cancer Center, Albuquerque, NM 87131, USA.
Carolyn Y
CY
Muller
Dept. of OB/GYN, University of Iowa, Iowa City, IA 52242, USA.
David P
DP
Bender
Dept. of Gynecologic Oncology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Robert L
RL
DeBernardo
Dept. of OB/GYN, University of Colorado Anschutz Medical Campus, School of Medicine, Aurora, CO 80045, USA.
Kian
K
Behbakht
Dept. of OB/GYN, University of Alabama School of Medicine, Birmingham, AL 35233-7333, USA.
Warner K
WK
Huh
D000230:Adenocarcinoma / Q000628:therapy*; D000328:Adult; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000628:therapy; D000077216:Carcinoma, Ovarian Epithelial; D002784:Cholesterol / Q000627:therapeutic use; D018284:Cystadenocarcinoma, Serous / Q000628:therapy; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005185:Fallopian Tube Neoplasms / Q000628:therapy*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007263:Infusions, Parenteral; D018664:Interleukin-12 / Q000235:genetics / Q000627:therapeutic use*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D009375:Neoplasms, Glandular and Epithelial / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000628:therapy*; D010534:Peritoneal Neoplasms / Q000628:therapy*; D010957:Plasmids / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011094:Polyethyleneimine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
C544016:poly(ethylene glycol)-co-poly(ethyleneimine); D018664:Interleukin-12; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D002784:Cholesterol
Gene therapy; Ovarian cancer; Phase II trial