EGEN-001 in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

Study Overview
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Brief Summary
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This phase II trial studies the side effects and how well EGEN-001 works in treating patients with ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer that is persistent or has come back. Biological therapies, such as EGEN-001, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop tumor cells from growing.

Detailed Description
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PRIMARY OBJECTIVES: I. To estimate the proportion of patients who survive progression-free for at least 6 months and the proportion of patients who have objective tumor response (complete or partial) in patients with persistent or recurrent ovarian epithelial, fallopian tube, or primary peritoneal carcinoma. II. To determine the frequency and severity of adverse events as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. SECONDARY OBJECTIVES: I. To determine the duration of progression-free survival and overall survival. TERTIARY OBJECTIVES: I. To collect blood and peritoneal lavage fluid from patients that will be stored for future research. OUTLINE: Patients receive intraperitoneal EGEN-001 on days 1, 8, 15, and 22. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Official Title
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A Phase II Evaluation of Intraperitoneal EGEN-001 (IL-12 Plasmid Formulated With PEG-PEI-Cholesterol Lipopolymer) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Conditions
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Fallopian Tube Carcinoma, Primary Peritoneal Carcinoma, Recurrent Ovarian Carcinoma

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Biological: PEG-PEI-cholesterol Lipopolymer-encased IL-12 DNA Plasmid Vector GEN-1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma; histologic documentation of the original primary tumor is required via the pathology report All patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (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 must have evidence of intra-abdominal/pelvic disease; patients with disease exclusively located outside of the abdominal/pelvic cavity are not eligible Patient must have 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 not be eligible for a higher priority Gynecologic Oncology Group (GOG) protocol, if one exists; in general, this would refer to any active GOG phase III protocol for the same patient population Patients who have received one prior regimen must have a GOG performance status of 0, 1, or 2 Patients who have received two prior regimens must have a GOG performance status of 0 or 1 Recovery from effects of recent surgery, radiotherapy, or chemotherapy: Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI]) 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 chemotherapy, biologic/targeted therapy and immunologic agents, must be discontinued at least three weeks prior to registration 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 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, or have progressed during platinum-based therapy, or have persistent disease after a platinum-based therapy Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease according to the following definition: Cytotoxic regimens include any agent that targets the genetic and/or mitotic apparatus of dividing cells, resulting in dose-limiting toxicity to the bone marrow and/or gastrointestinal mucosa Note: patients on this non-cytotoxic study are allowed to receive additional cytotoxic chemotherapy for management of recurrent or persistent disease, as defined above; however, due to the novel nature of biologic compounds, patients are encouraged to enroll on second-line non-cytotoxic studies prior to receiving additional cytotoxic therapy Absolute neutrophil count (ANC) greater or equal to 1,500/mcl Platelet count greater or equal to 100,000/mcl Creatinine less than or equal to 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance greater than or equal to 50 mL/min; any evidence of renal obstruction must be corrected prior to treatment Bilirubin less than or equal to 1.5 x ULN Serum glutamic oxaloacetic transaminase (SGOT) aspartate aminotransferase (AST) less than or equal to 3 x ULN Alkaline phosphatase less than or equal to 2.5 x ULN Neuropathy (sensory or motor) less than or equal to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 Patients must have signed an approved informed consent and authorization permitting release of personal health information Patients must meet pre-entry requirements Patients of childbearing potential must have a negative serum pregnancy test prior to the study entry and be practicing an effective form of contraception Exclusion Criteria: Patients who have had previous treatment with EGEN-001 Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies as noted above are excluded if there is any evidence of other malignancy being present within the last three years; patients are also 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 OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last three years 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 for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last three years 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 Patients with a past history of primary endometrial cancer are excluded unless all of the following conditions are met: stage not greater than I-B; no more than superficial myometrial invasion, without 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 Patients with a serious uncontrolled medical illness or disorder, abdominal surgery (for reasons other than IP port placement) or active infection within four weeks of study entry; patients may have surgery for the purpose of IP port placement greater than or equal to one week(s) before study entry and treatment Patients with any condition/anomaly that would interfere with the appropriate placement of the 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 Patients who are pregnant or breastfeeding

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (EGEN-001)<br>Patients receive intraperitoneal EGEN-001 on days 1, 8, 15, and 22. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Biological: PEG-PEI-cholesterol Lipopolymer-encased IL-12 DNA Plasmid Vector GEN-1<br>* Given intraperitoneally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients Who Survive Progression-free for at Least 6 Months | Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression was based on RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression | Every other cycle during treatment, then every 3 months until disese progression is confirmed, up to 5 years | 
| Patients Who Have Objective Tumor Response (Complete or Partial Response) | Complete and Partial Tumor Response by RECIST 1.1. Per Response Evaluation Criteria in Solid Tumors (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | CT or MRI used to follow lesion for measurable disease every other cycle. Patient's best response while on study treatment was recorded, Up to 5 years | 
| Adverse Events Deemed at Least Possibly Related to Treatment, as Assessed by NCI CTCAE Version 4.0 | Adverse events are listed by adverse event and grade. The number of participants affected is listed. | All Adverse Events (AEs) deemed at least possibly related to study treatmetn occurring during treatment and up to 30 days after stopping the study treatment. for up to 5 years after stopping study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The observed length of life from entry into the study to death or the date of last contact. | The duration of time from start of treatment to time of death or the date of last contact, assessed up to 5 years | 
| Progression-free Survival | The time from entry until disease progression, death, or date of last contact. Endpoints are progression or death. Patients who are not observed with an endpoint are censored. | The duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up to 5 years |