Safety Study of phIL-12-005/PPC to Treat Recurrent Ovarian Cancer

This study has been terminated.
(Sponsor decided to terminate the study early so they could begin a second dose-escalation study of EGEN-001 in combination with standard chemotherapy.)
Sponsor:
Information provided by (Responsible Party):
EGEN, Inc.
ClinicalTrials.gov Identifier:
NCT00137865
First received: August 26, 2005
Last updated: February 27, 2013
Last verified: February 2013
  Purpose

Ovarian cancer may be caused by a build-up of genetic defects, or damaged genes within the cells of the body. Because the genes are damaged, the body is unable to produce a group of proteins called cytokines which are used by the immune system to fight cancer and some infections. The investigational gene transfer agent EGEN-001 (phIL-12-005/PPC) contains the human gene for interleukin-12 [IL-12] (a cytokine) in a special carrier system designed to enter the cells and help the body produce cytokines.

This study has two purposes; the first is to determine what different strengths of EGEN-001 can be given safely without major side effects, and the second is to see if EGEN-001 is able to slow down the growth of ovarian cancer.


Condition Intervention Phase
Ovarian Neoplasms
Genetic: EGEN-001 (phIL-12-005/PPC)
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 1, Open Label, Dose Escalation Study of the Safety, Tolerability and Preliminary Efficacy of Intraperitoneal EGEN-001 in Patients With Recurrent Epithelial Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by EGEN, Inc.:

Primary Outcome Measures:
  • To determine the maximum tolerated dose (MTD) and to assess the spectrum of toxicities of EGEN-001 when administered by intraperitoneal (IP) infusion in patients with recurrent epithelial ovarian cancer [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess the preliminary efficacy of EGEN-001 by monitoring detectable tumor burden in patients with recurrent epithelial cancer
  • To assess EGEN-001 distribution by measuring human interleukin-12 plasmid (phIL-12) DNA copy number in the blood and peritoneal fluid
  • To assess the biological effects of EGEN-001 on cytokine production by measuring interferon (IFN) gamma and interleukin-12 (IL-12) concentrations in the blood and peritoneal fluid

Enrollment: 18
Study Start Date: August 2005
Study Completion Date: October 2006
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EGEN-001 Genetic: EGEN-001 (phIL-12-005/PPC)

Detailed Description:

EGEN-001-101 is a Phase 1, open label, non-randomized, dose escalation study in up to 18 (eighteen) patients (three to six patients in each of the first three cohorts, and up to nine patients in a fourth cohort or MTD). The fourth cohort (or MTD, if earlier) will be expanded in increments of three patients until a total of 18 patients have been enrolled.

Each patient will provide written dated informed consent prior to undergoing eligibility screening for entry into the study. Screening evaluations will be performed within 21 days prior to scheduled study drug administration. If all eligibility criteria are met, the patient will be enrolled and will be scheduled for placement of the IP catheter at least 7 days prior to the scheduled dosing (Day -7) to allow adequate time for healing around the catheter insertion site. Baseline evaluations will be performed prior to dosing. At that time the investigator will ensure that the patient remains eligible for participation.

All study drug will be administered on an inpatient basis and the patient will remain confined for 24 hours following study drug administration for evaluation of safety and collection of specified body fluid samples for plasmid IL-12-DNA and cytokine determinations. Each patient will receive the same dose of EGEN-001 once weekly for four weeks (administered on Day 0, Day 7, Day 14, and Day 21). Patients will undergo safety evaluations 1, 4 and 24 hours and 3 days following each dose. Patients will return to the clinic for safety evaluations three days, one week and five weeks (± one week) following the last dose.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female and at least 19 years of age (or minimum legal age and competency to provide voluntary written informed consent for study participation)
  • Have received previous treatment for ovarian cancer that included a platinum based chemotherapy regimen
  • Have recurrent epithelial ovarian cancer
  • Have a measurable tumor by computed tomography (CT) scan according to Response Evaluation Criteria in Solid Tumors (RECIST)
  • Have an ECOG performance status score of 0, 1, or 2
  • If of childbearing potential, agree to follow an acceptable method of birth control (e.g., abstinence, intrauterine device [IUD] or barrier method), as determined by the investigator, for the duration of the study. Hormonal contraceptives should not be used as the sole method of birth control.
  • Have normal organ and marrow function as defined below:

    • Leukocytes ≥ 3,000/µL;
    • Absolute neutrophil count ≥ 1,500/µL;
    • Platelets ≥ 100,000/µL;
    • Total bilirubin within institutional limits;
    • SGOT/SGPT ≤ 2.5 X institutional upper limit of normal (ULN);
    • Creatinine within institutional normal limits; OR creatinine clearance ≥ 60mL/min/1.73m2 for patients with creatinine levels above institutional normal.
  • Have electrocardiogram (ECG) without clinically significant abnormality, as determined by a qualified cardiologist
  • Have the capability (caregiver) of performing IP site care while at home

Exclusion Criteria:

  • A serious uncontrolled intercurrent medical illness or disorder including, but not limited to, ongoing or active infection, abdominal surgery, autoimmune disorders, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations which would limit compliance with study requirements
  • Intraabdominal disease > 5 (five) centimeters in diameter
  • Previous treatment with whole abdominal irradiation
  • Intestinal dysfunction or suspected extensive adhesions from prior history or findings at laparoscopy
  • Intrahepatic disease
  • Any condition/anomaly that would interfere with the appropriate placement of the IP catheter for study drug administration
  • Received investigational agents within three months prior to study drug dosing
  • Receipt of any medications (in particular, systemic or topical steroids) or substances known to affect, or with the potential to affect, the activity of EGEN-001
  • Life expectancy of less than three months
  • Known human immunodeficiency virus (HIV) infection
  • Positive HbsAg
  • Positive hepatitis C virus (HCV) serology
  • Prior IP drug administration
  • Prior immunotherapy for ovarian cancer
  • Chemotherapy within four weeks prior to placement of IP catheter
  • Radiotherapy within eight weeks prior to placement of IP catheter
  • Contraindication (either allergy or impaired renal function) to injection with contrast media for adequate evaluation of tumor size by CT scan
  • Pregnant or breast feeding an infant
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00137865

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
Sponsors and Collaborators
EGEN, Inc.
Investigators
Principal Investigator: Ronald Alvarez, MD Divison of Gynecologic Oncology at University of Alabama at Birmingham
  More Information

No publications provided

Responsible Party: EGEN, Inc.
ClinicalTrials.gov Identifier: NCT00137865     History of Changes
Other Study ID Numbers: EGEN-001-101
Study First Received: August 26, 2005
Last Updated: February 27, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on April 17, 2014