Study of IMNN-001 (Also Known as GEN-1) With NACT for Treatment of Ovarian Cancer (OVATION 2)

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Epithelial Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer

Intervention / Treatment
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* Biological: IMNN-001
* Drug: Carboplatin
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Patients must have an International Federation of Gynecology and Obstetrics (FIGO) of III or IV. 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 adequate: 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. Renal function: Creatinine ≤1.5 x institutional upper limit normal (ULN). Hepatic function: Bilirubin ≤ 1.5 x ULN. SGOT (AST) and SGPT (ALT) ≤ 3.0 x ULN and alkaline phosphatase ≤ 2.5 x ULN. Neurologic function: Neuropathy (sensory and motor) less than or equal to Grade 1. Patients should be free of active infection requiring parenteral antibiotics or a serious uncontrolled medical illness or disorder within four weeks of study entry. 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. Patients must have a performance status score of 0, 1 or 2 by Eastern Cooperative Group (ECOG) criteria. 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. Patients must have satisfactory results for the baseline laboratory analyses and diagnostic procedures as specified in the protocol. Patients must have signed an IRB-approved informed consent and authorization permitting release of personal health information. Patients must be at least 18 years old. Exclusion Criteria: Patients who have received prior treatment with IMNN-001. History of allergic reactions attributed to compounds of similar chemical or biologic composition to IMNN-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 such as chronic steroid use not related to chemotherapy administration. 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 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. 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 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 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. 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.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NACT + IMNN-001<br>The NACT regimen will be paclitaxel 175 mg/m2 IV over 3 hours followed by carboplatin AUC 6 IV over 1 hour on Day 1. This will be repeated every 3 weeks for 6 cycles. IMNN-001 100 mg/m2 IP will be administered on Days 8 and 15 of the first NACT cycle and then on Days 1, 8, and 15 of the subsequent 21 day NACT cycles for a total of 17 treatments. | Biological: IMNN-001<br>* IL-12 Plasmid Formulated with PEG-PEI-Cholesterol Lipopolymer<br>Drug: Carboplatin<br>* AUC 6 IV over 1 hour on Day 1 of each cycle<br>Drug: Paclitaxel<br>* 175 mg/m2 IV over 3 hours on Day 1 of each cycle<br>|
| Active Comparator: NACT Alone<br>The NACT regimen will be paclitaxel 175 mg/m2 IV over 3 hours followed by carboplatin AUC 6 IV over 1 hour on Day 1. This will be repeated every 3 weeks for 6 cycles. | Drug: Carboplatin<br>* AUC 6 IV over 1 hour on Day 1 of each cycle<br>Drug: Paclitaxel<br>* 175 mg/m2 IV over 3 hours on Day 1 of each cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | The primary objective of the study is to evaluate safety and compare progression free survival between subjects receiving neoadjuvant chemotherapy (NACT) plus IMNN-001 versus standard NACT. | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GEN-1, IMNN-001