Safety and Efficacy of EGEN-001 Combined With Carboplatin and Docetaxel in Recurrent, Platinum-Sensitive, Ovarian Cancer

Study Overview
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Brief Summary
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Ovarian cancer may be caused by a build-up of genetic defects, or damaged genes within the body's cells. When genes are damaged, the body may be unable to produce a group of proteins, called cytokines, used by the immune system to fight cancer and some infections. The investigational gene transfer agent EGEN-001 contains the human gene for the cytokine interleukin-12 (IL-12) in a special carrier system designed to enter the cells and help the body to produce cytokines. Therefore, the purpose of the EGEN-001 therapy is to attempt to enhance the body's natural ability to recognize and fight cancer cells. Funding Source - FDA OOPD

Detailed Description
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This study has two purposes: To determine what different strengths and number of doses of EGEN-001, administered directly into the peritoneal cavity, can be given safely in combination with standard intravenous chemotherapy for ovarian cancer To evaluate the anti-cancer activity of EGEN-001 when combined with standard chemotherapy; biological markers of EGEN-001 activity will be collected and ovarian cancer burden will be evaluated per standard practice.

Official Title
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A Phase 1, Open-Label, Dose Escalation Study of the Safety and Preliminary Efficacy of EGEN-001 in Combination With Carboplatin and Docetaxel in Women With Recurrent, Platinum-Sensitive, Epithelial Ovarian Cancer

Conditions
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Ovarian Neoplasms

Intervention / Treatment
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* Genetic: EGEN-001 (phIL-12-005/PPC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be female and at least 18 years of age (or minimum legal age and competency to provide voluntary written informed consent for study participation); Histologically/cytologically confirmed epithelial ovarian cancer that meets one of the following criteria: measurable disease by computed tomography (CT) scan or malignant ascites, or Serum CA-125 levels; or Clinically evaluable recurrent disease by other criteria. Relapsed, platinum-sensitive, ovarian cancer after induction chemotherapy (at least 6 months since last exposure to platinum based therapy). Eastern Cooperative Oncology Group (ECOG) Performance score of 0, 1 or 2; Recovered from prior chemotherapy, having adequate bone marrow function: Adequate renal function; Adequate liver function; If of childbearing potential, have a negative pregnancy test and agree to follow an acceptable method of birth control; Agree to be compliant with the study's requirements; Understand and sign a written Informed Consent prior to the performance of any study-related procedures. Exclusion Criteria: Ovarian cancer other than documented epithelial cancer; Intra-abdominal disease > 5 cm in diameter; Any serious, uncontrolled, intercurrent medical illness or disorder including, but not limited to: Autoimmune disorders Cardiac Disorders Diabetes Intrahepatic disease/cancer as documented by CT-scan An active infection within 4 weeks of study entry; Any condition/anomaly that would interfere with the appropriate placement of the IP catheter for study drug administration Prior treatment with whole abdominal irradiation; Currently receiving or have received any investigational agents within 28 days of study entry; Received prior chemotherapy for ovarian cancer administered by the IP route; Received any chemotherapy between completion of primary chemotherapy for ovarian cancer and study entry (e.g. consolidation therapy); Receipt of immunotherapy and/or any medications with the potential to affect the activity of EGEN 001; Known history of HIV infection, hepatitis B, or hepatitis C; Known hypersensitivity to any of the components of carboplatin or docetaxel; Life expectancy of less than 3 months; Known, current, recreational drug or alcohol abuse; Breast feeding an infant; Psychiatric illness/social situations which would limit compliance with study requirements; Any other known condition which in the Investigator's opinion would make the patient a poor candidate for the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EGEN-001<br> | Genetic: EGEN-001 (phIL-12-005/PPC)<br>* In stage 1, patients will receive standard doses of IV carboplatin and docetaxel for 2 treatment cycles with a 3 week interval. Patients will also receive 4 IP infusions of EGEN-001 at 12mg/m2 EGEN-001, 18mg/m2, or 24mg/m2, 10-11 days apart. Stage 2 of the study will involve cycle escalation at the highest EGEN-001 dose identified from Stage 1. All patients will receive up to 8 doses of EGEN-001, 10-11 days apart plus up to 4 IV carboplatin and docetaxel cycles with 3 week intervals. After receiving the assigned number of treatments of EGEN-001, carboplatin, and docetaxel, patients may continue to receive up to 4 additional infusions of EGEN-001 and 2 IV carboplatin and docetaxel cycles with 3 week intervals.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the MTD and treatment-related toxicities of intra-peritoneal (IP) infusion of EGEN-001 in combination with carboplatin and docetaxel for recurrent, platinum-sensitive, ovarian cancer. |  | 12-14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Examine the optimal EGEN-001 treatment regimen in combination with carboplatin and docetaxel in recurrent, platinum-sensitive ovarian cancer, and assess EGEN-001's impact on tumor, CA-125, and activity markers of biological activity. |  | 10 months |