Ovarian Cancer Clinical Trial

EGEN-001 and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

Summary

This phase I trial studies the side effects and the best dose of giving EGEN-001 together with pegylated liposomal doxorubicin hydrochloride in treating patients with ovarian epithelial, fallopian tube, or primary peritoneal cancer that has returned after a period of improvement or has not responded to treatment. Biological therapies, such as EGEN-001, may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving EGEN-001 together with pegylated liposomal doxorubicin hydrochloride may kill more tumor cells.

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Full Description

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of EGEN-001 when administered in combination with pegylated liposomal doxorubicin hydrochloride (PLD; Doxil; Lipodox) every 28 days and the associated DLTs based on adverse events that occur in cycle 1 for this combination in women with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

II. To examine the tolerability of the combination at the MTD of EGEN-001 assessed in combination with PLD.

III. To determine recommended phase II dose (RP2D) of EGEN-001 in combination with PLD.

SECONDARY OBJECTIVES:

I. To estimate the objective response rate (complete and partial) in patients with measurable disease.

TERTIARY OBJECTIVES:

I. Determine the levels and time course of interleukin-12 (IL-12), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) and vascular endothelial growth factor (VEGF) following EGEN-001 treatment.

II. Assess the effect of EGEN-001 treatment on the nature of the cellular immune responses by measuring cell-specific ribonucleic acid (RNA) transcripts.

OUTLINE: This is a dose-escalation study of EGEN-001.

Patients receive pegylated liposomal doxorubicin hydrochloride intravenously (IV) over 60 minutes on day 1 and EGEN-001 intraperitoneally (IP) over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up quarterly for up to 1 year.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Patients must have histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma which is now persistent or 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
Absolute neutrophil count (ANC) >= 1,500/mcl; this ANC cannot have been induced or supported by granulocyte colony-stimulating factors
Platelets >= 100,000/mcl
Creatinine =< 1.5 times institutional upper limit of normal (ULN)
Bilirubin =< 1.5 times ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x ULN
Alkaline phosphatase =< 2.5 x ULN
Left ventricular ejection fraction (LVEF) greater than or equal to institutional lower limit of normal (LLN) as determined by gated cardiac radionucleotide scan (multi-gated acquisition scan [MUGA]) or echocardiogram
Neuropathy (sensory and motor) less than or equal to grade 1
Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy
Patients should be free of active infection requiring parenteral antibiotics
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 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 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 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
Gynecology Oncology Group (GOG) performance status of 0 or 1
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
Patients who have met the pre-entry requirements
Patients must have signed an Institutional Review Board (IRB)-approved informed consent and authorization permitting release of personal health information

Exclusion Criteria:

Patients who have received prior treatment with EGEN-001
Patients who have received prior PLD, doxorubicin, or other anthracyclines
History of allergic reactions attributed to compounds of similar chemical or biologic composition to EGEN-001 or other agents used in this study
Patients who have received oral or parenteral corticosteroids within 2 weeks of study entry or who have a clinical requirement for ongoing systemic immunosuppressive therapy
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 with other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies as noted below 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 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
Patients with known active hepatitis
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
Patients of childbearing potential, not practicing adequate contraception, patients who are pregnant, or patients who are breastfeeding are not eligible for this trial
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
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)
Corrected QT (QTc) interval >= 450 ms on baseline EKG (electrocardiogram)
Baseline ejection fraction =< 50% as assessed by echocardiogram or multi gated acquisition scan (MUGA)
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)
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

Study is for people with:

Ovarian Cancer

Phase:

Phase 1

Estimated Enrollment:

16

Study ID:

NCT01489371

Recruitment Status:

Completed

Sponsor:

Gynecologic Oncology Group

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There are 7 Locations for this study

See Locations Near You

University of Alabama at Birmingham Cancer Center
Birmingham Alabama, 35233, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange California, 92868, United States
Washington University School of Medicine
Saint Louis Missouri, 63110, United States
University of New Mexico Cancer Center
Albuquerque New Mexico, 87102, United States
Case Western Reserve University
Cleveland Ohio, 44106, United States
University of Oklahoma Health Sciences Center
Oklahoma City Oklahoma, 73104, United States
Froedtert and the Medical College of Wisconsin
Milwaukee Wisconsin, 53226, United States

How clear is this clinincal trial information?

Study is for people with:

Ovarian Cancer

Phase:

Phase 1

Estimated Enrollment:

16

Study ID:

NCT01489371

Recruitment Status:

Completed

Sponsor:


Gynecologic Oncology Group

How clear is this clinincal trial information?

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