A Phase I Study of Intraperitoneal EGEN-001 (IL-12 Plasmid Formulated With PEG-PEI-Cholesterol Lipopolymer) (IND #12,484) Administered in Combination With Pegylated Liposomal Doxorubicin (PLD, Doxil (NSC #712227 or Lipodox) in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Patients must have histologic diagnosis of epithelial ovarian, fallopian tube, or
primary peritoneal carcinoma which is now recurrent; histologic documentation of the
original primary tumor is required via the pathology report

- Patients with the following histologic epithelial cell types are eligible: high-grade
serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear
cell adenocarcinoma, mixed epithelial carcinoma, or adenocarcinoma not otherwise
specified (N.O.S.)

- Patients must have recurrence documented by elevated CA-125 (biochemical recurrence)
or clinically evident measurable or non-measurable recurrent disease as defined
below:

- Biochemical recurrence is defined as a CA-125 greater than or equal to two times
the upper normal limit; patients whose CA-125 is less than 100 U/mL must undergo
a second confirmatory value within a period of not more than 4 weeks; patients
with a level greater than or equal to 100 U/mL may be entered without
confirmatory measurement; the CA-125 assessment for eligibility must be done at
least 4 weeks after paracentesis or other surgical procedures

- Detectable (non-measurable) disease is defined as symptomatic ascites or pleural
effusions, solid and/or cystic abnormalities on radiographic imaging that do not
meet RECIST 1.1 definitions for target lesions and/or biopsy-proven recurrence

- Measurable disease will be defined by RECIST 1.1; measurable disease is defined
as at least one lesion that can be accurately measured in at least one dimension
(longest diameter to be recorded); each lesion must be ≥ 10 mm when measured by
computed tomography (CT), magnetic resonance imaging (MRI), or caliper
measurement by clinical exam; or ≥ 20 mm when measured by chest x-ray; lymph
nodes must be ≥ 15 mm in short axis when measured by CT or MRI

- Patients with measurable disease must have had at least one "target lesion"
to be used to assess response on this protocol as defined by RECIST 1.1;
tumors within a previously irradiated field will be designated as
"non-target" lesions unless progression is documented or a biopsy is
obtained to confirm persistence at least 90 days following completion of
radiation therapy

- Patients must have had one prior platinum-based chemotherapeutic regimen for
management of primary disease containing carboplatin, cisplatin, or another
organoplatinum compound; this initial treatment may have included intraperitoneal
therapy, consolidation, non-cytotoxic agents, or extended therapy administered after
surgical or non-surgical assessment

- No patients with synchronous primary endometrial cancer or a past history of
endometrial cancer, unless all of the following conditions are met:

- Stage not greater than IB

- No more than superficial myometrial invasion

- No vascular or lymphatic invasion

- No poorly differentiated subtypes, including papillary serous, clear cell, or
other International Federation of Gynecology and Obstetrics (FIGO) Grade 3
lesions

- No patients with history or evidence upon physical examination of central nervous
system (CNS) disease, including primary brain tumor, seizures not controlled with
standard medical therapy, any brain metastases, or history of cerebrovascular
accident (CVA, stroke), transient ischemic attack (TIA), or subarachnoid hemorrhage
within six months of the first date of treatment on this study

PATIENT CHARACTERISTICS:

- GOG performance status of 0 or 1

- Absolute neutrophil count (ANC) ≥ 1,500/mcl; this ANC cannot have been induced or
supported by granulocyte colony-stimulating factors

- Platelets greater than or equal to 100,000/mcl

- Creatinine ≤ 1.5 times institutional upper limit of normal (ULN)

- Bilirubin ≤ 1.5 times ULN

- AST and ALT ≤ 3.0 times ULN

- Alkaline phosphatase ≤ 2.5 times ULN

- Left ventricular ejection fraction (LVEF) greater than or equal to institutional
lower limit of normal (LLN) as determined by gated cardiac radionucleotide scan
(MUGA) or echocardiogram

- Neuropathy (sensory and motor) less than or equal to Grade 1

- Patients should be free of active infection requiring parenteral antibiotics

- Patients of childbearing potential must have a negative pregnancy test prior to the
study entry and be practicing an effective form of contraception; if applicable,
patients must discontinue breastfeeding prior to study entry

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to EGEN-001 or other agents used in this study

- No patients with other invasive malignancies, with the exception of non-melanoma skin
cancer and other specific malignancies, if there is any evidence of the other
malignancy being present within the last three years

- No patients with known active hepatitis

- No patients with concurrent severe medical problems unrelated to the malignancy that
would significantly limit full compliance with the study or expose the patient to
extreme risk or decreased life expectancy

- No patients with clinically significant cardiovascular disease; this includes:

- Uncontrolled hypertension, defined as systolic > 140 mm Hg or diastolic > 90 mm
Hg

- Myocardial infarction or unstable angina within 6 months prior to registration

- History of serious ventricular arrhythmia (i.e., ventricular tachycardia or
ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic
medications (except for atrial fibrillation that is well controlled with
anti-arrhythmic medication)

- New York Heart Association (NYHA) Class II or higher congestive heart failure

- Grade 2 or higher peripheral ischemia [brief (< 24 hrs) episode of ischemia
managed non-surgically and without permanent deficit]

- QTc interval ≥ 450 ms on baseline EKG (electrocardiogram)

- No patients with any condition/anomaly that would interfere with the appropriate
placement of the intraperitoneal (IP) catheter for study drug administration
including: abdominal surgery within 4 weeks of study entry (for reasons other than IP
port placement), intestinal dysfunction, or suspected extensive adhesions from prior
history or finding at laparoscopy

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Patients must have recovered from effects of recent surgery, radiotherapy, or
chemotherapy

- Any hormonal therapy directed at the malignant tumor must be discontinued at least
one week prior to registration; continuation of hormone-replacement therapy is
permitted

- Any other prior therapy directed at the malignant tumor, including biological and
immunologic agents, must be discontinued at least three weeks prior to registration

- Patients are allowed to receive, but are not required to receive, two additional
cytotoxic regimens for management of recurrent or persistent disease, with no more
than 1 non-platinum, non-taxane regimen

- Prior treatment with pegylated liposomal doxorubicin hydrochloride [Doxil] or other
anthracyclines is NOT allowed

- Patients are allowed to receive, but are not required to receive, non-cytotoxic
therapy (such as bevacizumab) as part of their primary treatment regimen

- Patients are allowed to receive, but are not required to receive, non-cytotoxic
therapy for management of recurrent or persistent disease

- Patients who have received only one prior cytotoxic regimen (platinum-based regimen
for management of primary disease), must have a platinum-free interval of less than
12 months, have progressed during platinum-based therapy, or have persistent disease
after a platinum-based therapy

- No patients who have received prior treatment with EGEN-001

- No patients who have received oral or parenteral corticosteroids within 2 weeks of
study entry or who require ongoing systemic immunosuppressive therapy for any reason

- No patients receiving treatment for active autoimmune disease; "active" refers to any
condition currently requiring therapy; examples of autoimmune disease include
systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, and
rheumatoid arthritis

- Patients are excluded if their previous cancer treatment contraindicates this
protocol therapy

- Patients who have received prior radiotherapy to any portion of the abdominal cavity
or pelvis are excluded

- Prior radiation for localized cancer of the breast, head and neck, or skin is
permitted, provided that it was completed more than three years prior to
registration, and the patient remains free of recurrent or metastatic disease

- Patients who have received prior chemotherapy for any abdominal or pelvic tumor
(other than ovarian, fallopian tube and primary peritoneal) are excluded

- Patients may have received prior adjuvant chemotherapy for localized breast
cancer, provided that it was completed more than three years prior to
registration, and that the patient remains free of recurrent or metastatic
disease