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

NCT01489371 | Completed Phase 1

• 5 other identifiers: GOG-9928NCI-2012-00088CDR0000719230U10CA180868U10CA027469
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

Outcome Measures

Primary Outcomes (2)

• First course DLTs

  28 days

• The grade of toxicity as assessed by CTCAE v 4.0

  Up to 1 year

Secondary Outcomes (1)

• Objective tumor response (complete and partial response)

  Up to 1 year

Other Outcomes (2)

• Change in biomarker levels

  Baseline to up to 1 year

• Change in cellular immune response as measured by cell-specific RNA transcripts

  Baseline to up to 1 year

Study Arms (1)

Treatment (EGEN-001, pegylated liposomal doxorubicin)

EXPERIMENTAL

Patients receive pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 and EGEN-001 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.

Other: Laboratory Biomarker Analysis; Biological: PEG-PEI-cholesterol Lipopolymer-encased IL-12 DNA Plasmid Vector GEN-1; Drug: Pegylated Liposomal Doxorubicin Hydrochloride

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (EGEN-001, pegylated liposomal doxorubicin)

PEG-PEI-cholesterol Lipopolymer-encased IL-12 DNA Plasmid Vector GEN-1 BIOLOGICAL

Given IP

Also known as: GEN-1, IL-12 Plasmid Formulated With PEG-PEI-Cholesterol Lipopolymer, Nanoparticle-encased IL-12 DNA Plasmid Vector, phIL-12-005

Treatment (EGEN-001, pegylated liposomal doxorubicin)

Pegylated Liposomal Doxorubicin Hydrochloride DRUG

Given IV

Also known as: ATI-0918, Caelyx, DOX-SL, Doxil, Doxilen, Doxorubicin HCl Liposome, doxorubicin hydrochloride liposome, Duomeisu, Evacet, LipoDox, Liposomal Adriamycin, liposomal doxorubicin hydrochloride, Liposomal-Encapsulated Doxorubicin, Pegylated Doxorubicin HCl Liposome, S-Liposomal Doxorubicin, Stealth Liposomal Doxorubicin, TLC D-99

Treatment (EGEN-001, pegylated liposomal doxorubicin)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Gynecologic Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (7)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87102, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

GEN-1; liposomal doxorubicin; Doxorubicin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Premal H Thaker

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2011
• First Posted: December 9, 2011
• Study Start: July 9, 2012
• Primary Completion: December 30, 2014
• Study Completion: January 27, 2018
• Last Updated: March 12, 2019

Record last verified: 2019-03

Locations

US (7)