Study of GEN-1 With NACT for Treatment of Ovarian Cancer (OVATION 2) (OVATION 2)

• ClinicalTrials.gov Identifier: NCT03393884
• Recruitment Status: Recruiting
• First Posted: January 9, 2018
• Last Update Posted: March 9, 2022
• Sponsor: Celsion
• Information provided by (Responsible Party): Celsion

Tracking Information

• First Submitted Date: January 3, 2018
• First Posted Date: January 9, 2018
• Last Update Posted Date: March 9, 2022
• Actual Study Start Date: September 5, 2018
• Estimated Primary Completion Date: February 28, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 21, 2018)

PFS [ Time Frame: 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. ]

The primary objective of the study is to evaluate safety and compare progression free survival between subjects receiving neoadjuvant chemotherapy (NACT) plus GEN-1 versus standard NACT.

Original Primary Outcome Measures (submitted: January 3, 2018)

PFS [ Time Frame: The primary analysis for PFS will be conducted after at least 52 events have been observed or after all patients have been followed for at least 12 months, whichever is later. ]

The primary objective of the study is to evaluate safety and compare progression free survival between subjects receiving neoadjuvant chemotherapy (NACT) plus GEN-1 versus standard NACT.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of 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 GEN-1 (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
• Brief Summary: This is a randomized, open label, multicenter trial to evaluate the safety, dosing, efficacy and biological activity of intraperitoneal GEN-1 plus NACT compared to NACT alone.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Epithelial Ovarian Cancer
• Fallopian Tube Cancer
• Primary Peritoneal Cancer

Intervention

• Biological: GEN-1
  IL-12 Plasmid Formulated with PEG-PEI-Cholesterol Lipopolymer
• Drug: Carboplatin
  AUC 6 IV over 1 hour on Day 1 of each cycle
• Drug: Paclitaxel
  175 mg/m2 IV over 3 hours on Day 1 of each cycle

Study Arms

• Experimental: NACT + GEN-1
  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. GEN-1 100 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.
  Interventions:

  • Biological: GEN-1
  • Drug: Carboplatin
  • Drug: Paclitaxel
• Active Comparator: NACT Alone
  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.
  Interventions:

  • Drug: Carboplatin
  • Drug: Paclitaxel

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 31, 2018): 130
• Original Estimated Enrollment (submitted: January 3, 2018): 90
• Estimated Study Completion Date: December 31, 2024
• Estimated Primary Completion Date: February 28, 2023 (Final data collection date for primary outcome measure)

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 GEN-1.
2. History of allergic reactions attributed to compounds of similar chemical or biologic composition to GEN-1 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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Nicholas Borys, M.D.; 609-896-9100; nborys@celsion.com

Contact: Beth J Llewellyn; 609-896-9100; bllewellyn@celsion.com

• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT03393884
• Other Study ID Numbers: 201-17-201
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Celsion
• Original Responsible Party: Same as current
• Current Study Sponsor: Celsion
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Premal H. Thaker, M.D; Washington University School of Medicine

• PRS Account: Celsion
• Verification Date: March 2022