The purpose of this study is to determine if GL-ONC1 oncolytic immunotherapy is well tolerated with anti-tumor activity in patients diagnosed with recurrent or refractory ovarian cancer and peritoneal carcinomatosis.
Ovarian cancer (OC) remains the most lethal gynecologic malignancy owing to late detection, intrinsic and acquired chemo-resistance and remarkable heterogeneity. There is an unmet medical need to develop new therapy modalities. In preclinical studies, GL-ONC1, has shown the ability to preferentially locate, colonize and destroy tumor cells in more than 30 different human tumors, including ovarian cancer. GL-ONC1 has been investigated in early stage clinical trials in the United States and Europe via systemic delivery as monotherapy and in combination with other therapies, and via regional delivery as monotherapy. GL-ONC1 treatment was well tolerated across different malignancies, routes of administration, and monotherapy as well as combination therapy protocols. The ability of GL-ONC1 to infect tumor tissue and kill tumor cells was demonstrated. In addition, virus-induced immune activation and favorable anti-tumor immune response have been observed. Evidences of anti-tumor efficacy and clinical benefits have also been documented.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
46
GL-ONC1 is a genetically-engineered oncolytic vaccinia virus, which is administered via intraperitoneal infusion as multiple doses.
Gynecologic Oncology Associates
Newport Beach, California, United States
AdventHealth Cancer Institute
Orlando, Florida, United States
Incidence of Treatment-emergent Adverse Events [Safety and Tolerability] (Phase 1b)
Determine safety and tolerability of administering multiple doses of GL-ONC1 via intraperitoneal catheter by the evaluation of the number of participants with treatment-emergent adverse events (type, frequency, and severity) as assessed by CTCAE 4.03.
Time frame: Change from baseline during Treatment and for 30 days following last dose.
Determine Progression-free Survival following Treatment (Phase 2)
To assess progression-free survival (PFS) from time of registration until disease
Time frame: From date of registration until the date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to 24 months.
Tumor Marker Cancer Antigen-125 (CA-125) (Phase 2)
To assess anti-tumor response.
Time frame: Assessed pre-treatment, during treatment at 2- to 3-week intervals and post-treatment assessed up to 24 months.
Overall Response Rate (ORR) by RECIST 1.1 (Phase 2)
To assess anti-tumor response.
Time frame: Assessed pre-treatment, during treatment at 6- to 12-week intervals and post-treatment assessed up to 24 months.
Evaluation of Tumor Response to Treatment (Phase 1b)
Evaluate participant's best overall response to treatment with therapeutic intent assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (i.e., complete response, partial response, stable disease, or progressive disease).
Time frame: Assessed post-treatment at 6 to 12 week intervals or until disease progression or death from any cause, whichever comes first, assessed up to 24 months.
Evaluation of Immune-related Tumor Response
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Evaluate participants' best overall response to treatment with oncolytic immunotherapy assessed by Immune-related Response Criteria (immune-related complete response, immune-related partial response, immune-related stable disease, or immune-related progressive disease).
Time frame: Assessed post-treatment at 6 to 12 week intervals or until disease progression or death from any cause, whichever comes first, assessed up to 24 months.
CA-125 Response (Phase 1b)
CA-125 according to the Gynecologic Cancer Intergroup (GCIG) is measured by at least a 50% reduction in CA-125 levels from pre-treatment sample which is confirmed and maintained for at least 28 days. Pre-treatment CA-125 sample must be at least twice the upper limit of normal and obtained within 2 weeks prior to starting treatment.
Time frame: Assessed pre-treatment, during treatment and post-treatment at 6 to 12 week intervals, assessed up to 24 months.
Determine Progression-free Survival following Treatment (Phase 1b)
To assess progression-free survival (PFS) in participant population.
Time frame: From date of registration until the date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to 24 months.
Overall Survival
To determine overall survival (OS) in the participant population.
Time frame: By medical chart review until death or 3 years from the date of last treatment which ever comes first.
Clinical Benefit Rate
Defined as the percentage of patients who have achieved CR + PR + SD greater than or equal to 15 weeks.
Time frame: Approximately 24 months