Clinical trial NCT03393884: Study of IMNN-001 (Also Known as GEN-1) With NACT for Treatment of Ovarian Cancer (OVATION 2)
Official title: A Phase I/II Study Evaluating the Dosing, Safety, Efficacy, and Biological Activity of Intraperitoneal IMNN-001 (IL-12 Plasmid Formulated With PEG-PEI-Cholesterol Lipopolymer) Administered in Combination With Neoadjuvant Chemotherapy (NACT) in Patients Newly Diagnosed With Advanced Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Epithelial Ovarian Cancer
Fallopian Tube Cancer
Primary Peritoneal Cancer
Keywords: GEN-1
IMNN-001
Lead sponsor: Imunon
Sponsor class: INDUSTRY
First posted: 2018-01-09
Enrollment: 130
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, open label, multicenter trial to evaluate the safety, dosing, efficacy and biological activity of intraperitoneal IMNN-001 plus NACT compared to NACT alone.


Eligibility criteria: Inclusion Criteria:

1. Patients must have suspected histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma per pre-treatment biopsies by laparoscopy, or interventional radiology or CT guided core biopsy. Histologic documentation of the original primary tumor is required via the pathology report.
2. Patients must have an International Federation of Gynecology and Obstetrics (FIGO) of III or IV.
3. 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.).
4. Patients must have adequate:

   1. Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to 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.
   2. Renal function: Creatinine ≤1.5 x institutional upper limit normal (ULN).
   3. Hepatic function: Bilirubin ≤ 1.5 x ULN. SGOT (AST) and SGPT (ALT) ≤ 3.0 x ULN and alkaline phosphatase ≤ 2.5 x ULN.
   4. Neurologic function: Neuropathy (sensory and motor) less than or equal to Grade 1.
5. Patients should be free of active infection requiring parenteral antibiotics or a serious uncontrolled medical illness or disorder within four weeks of study entry.
6. Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to the first treatment. Continuation of hormone replacement therapy is permitted.
7. Patients must have a performance status score of 0, 1 or 2 by Eastern Cooperative Group (ECOG) criteria.
8. Patients of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of protocol therapy and be practicing an effective form of contraception. If applicable, patients must discontinue breastfeeding prior to study entry.
9. Patients must have satisfactory results for the baseline laboratory analyses and diagnostic procedures as specified in the protocol.
10. Patients must have signed an IRB-approved informed consent and authorization permitting release of personal health information.
11. Patients must be at least 18 years old.

Exclusion Criteria:

1. Patients who have received prior treatment with IMNN-001.
2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to IMNN-001 or other agents used in this study.
3. 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 such as chronic steroid use not related to chemotherapy administration.
4. 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.
5. Patients with other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies as noted in the protocol 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.
6. 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.
7. Patients who have received prior chemotherapy for any abdominal or pelvic tumor 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.
8. Patients with known active hepatitis.
9. 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.
10. Patients of childbearing potential, not practicing adequate contraception, patients who are pregnant, or patients who are breastfeeding are not eligible for this trial.
11. Patients with history or evidence upon physical examination of 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.
12. 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.

Primary outcomes:
measure: PFS
timeFrame: The primary analysis for PFS will be conducted after at least 80 events have been observed or after all patients have been followed for at least 16 months, whichever is later.
Secondary outcomes:
measure: Overall Survival
timeFrame: Randomization to date of death, for up to 3 years from LPI
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Mobile
country: United States
facility: Mitchell Cancer Institute (University of South Alabama)
state: Alabama
city: Newport Beach
country: United States
facility: Gynecologic Oncology Associates (Hoag Hospital)
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research
state: California
city: Orlando
country: United States
facility: Advent Health
state: Florida
city: Saint Petersburg
country: United States
facility: Women's Care Florida
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Camden
country: United States
facility: MD Anderson at Cooper
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Lake Success
country: United States
facility: Monter Cancer Center
state: New York
city: Mineola
country: United States
facility: NYU Langone, Long Island
state: New York
city: New York
country: United States
facility: NYU Langone
state: New York
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center - Oklahoma University
state: Oklahoma
city: Portland
country: United States
facility: Providence Cancer Institute
state: Oregon
city: Sioux Falls
country: United States
facility: Sanford Health
state: South Dakota
city: Chattanooga
country: United States
facility: Chattanooga Women's Health
state: Tennessee
city: Germantown
country: United States
facility: The West Clinic
state: Tennessee
city: Spokane
country: United States
facility: Providence Health Care
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Montréal
country: Canada
facility: CHUM
Study officials:
affiliation: Washington University School of Medicine
name: Premal H. Thaker, M.D
role: STUDY_CHAIR
References: