Clinical trial NCT02759588: GL-ONC1 Oncolytic Immunotherapy in Patients With Recurrent or Refractory Ovarian Cancer
Official title: Phase 1b & 2 Study With GL-ONC1 Oncolytic Immunotherapy in Patients With Recurrent or Refractory Ovarian Cancer (VIRO-15)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Ovarian Cancer
Peritoneal Carcinomatosis
Fallopian Tube Cancer
Keywords: GL-ONC1
oncolytic virus
virotherapy
Viral therapy
immunotherapy
immune therapy
vaccinia
vaccinia virus
Genelux
ovarian cancer
platinum resistant
platinum refractory
peritoneal carcinomatosis
fallopian cancer
cancer
abdominal cancer
imaging
carcinoma
DNA virus
neoplasms
neoplasms by histological type
neoplasms, Glandular and Epithelial
Poxviridae infections
Virus diseases
recurrent ovarian cancer
intermediate platinum-sensitive
Lead sponsor: Genelux Corporation
Sponsor class: INDUSTRY
First posted: 2016-05-03
Enrollment: 46
Sex: FEMALE
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Signed, written informed consent.
* High-grade serous (including Malignant Mixed Mullerian Tumor (MMMT) with metastasis that contains high grade epithelial carcinoma), endometrioid, or clear-cell ovarian cancer which includes: (1) platinum-resistant (recurrence or progression in \< 6 months) or (2) platinum-refractory (progression while on platinum-based therapy); patient must have failed either at least 2 consecutive therapies or are not eligible for additional cytotoxic therapies (exception is Phase 2 receiving chemotherapy with/without bevacizumab).
* Intermediate platinum-sensitive patients (recurrence of disease 6 to 12 months from last platinum compound treatment): Recurrent ovarian carcinoma with at least four prior individual treatment regimens including at least two separate platinum-based therapies with recurrence from the last platinum-based regimen less than 12 months, who are unwilling or unable to undergo additional platinum-based cytotoxic therapy (this sub-population is not applicable for Phase 2 receiving chemotherapy with/without bevacizumab).
* Performance status ECOG is at 0 or 1, and life expectancy of 6 months
* Has either measurable disease in the peritoneal cavity as defined by RECIST 1.1 (Phase 1b \& 2) or has non-measurable disease in the peritoneal cavity (Phase 1b) and can be confirmed by laparoscopy and/or elevated CA-125. Patients who have non-measurable disease that is not identifiable by PET/PET-CT scan, but who have elevated CA-125, and/or ascites, with visible disease confirmed by laparoscopy are also eligible.
* Able to undergo IP injection.
* Adequate renal, hepatic, bone marrow and immune functions.
* Baseline tumor biopsy is required.
* Documented progressive disease status at baseline (Phase 2).

Exclusion Criteria:

* Tumors of mucinous subtypes, or non-epithelial ovarian cancers (e.g., Brenner tumors, Sex-cord tumors).
* Unresolved bowel obstruction.
* Known central nervous system (CNS) metastasis.
* Known seropositivity for HIV or active hepatitis infection.
* History of thromboembolic event within the last 3 months.
* Pregnant or breast-feeding women.
* Smallpox vaccination within 1 year of study treatment.
* Clinically significant cardiac disease.
* Received prior gene therapy or therapy with cytolytic virus of any type.
* Receiving concurrent antiviral agent active against vaccinia virus.
* Have known allergy to ovalbumin or other egg products.
* Have clinically significant dermatological disorders (e.g., eczema, psoriasis, or unhealed skin wounds or ulcers) as assessed by the Investigator.
* Symptomatic malignant ascites and non-manageable pleural effusion.
* Known hypersensitivity to bevacizumab, uncontrolled hypertension, history of stroke, or clinical findings suggestive of excessive risk for GL perforation (uncontrolled peptic ulcer disease, partial small bowel obstruction, etc.) that would make risks of bevacizumab unacceptable in the opinion of the investigator.

Primary outcomes:
measure: Incidence of Treatment-emergent Adverse Events [Safety and Tolerability] (Phase 1b)
timeFrame: Change from baseline during Treatment and for 30 days following last dose.
measure: Determine Progression-free Survival following Treatment (Phase 2)
timeFrame: 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.
measure: Tumor Marker Cancer Antigen-125 (CA-125) (Phase 2)
timeFrame: Assessed pre-treatment, during treatment at 2- to 3-week intervals and post-treatment assessed up to 24 months.
measure: Overall Response Rate (ORR) by RECIST 1.1 (Phase 2)
timeFrame: Assessed pre-treatment, during treatment at 6- to 12-week intervals and post-treatment assessed up to 24 months.
Secondary outcomes:
measure: Evaluation of Tumor Response to Treatment (Phase 1b)
timeFrame: 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.
measure: Evaluation of Immune-related Tumor Response
timeFrame: 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.
measure: CA-125 Response (Phase 1b)
timeFrame: Assessed pre-treatment, during treatment and post-treatment at 6 to 12 week intervals, assessed up to 24 months.
measure: Determine Progression-free Survival following Treatment (Phase 1b)
timeFrame: 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.
measure: Overall Survival
timeFrame: By medical chart review until death or 3 years from the date of last treatment which ever comes first.
measure: Clinical Benefit Rate
timeFrame: Approximately 24 months
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Gynecologic Oncology Associates
state: California
city: Orlando
country: United States
facility: AdventHealth Cancer Institute
state: Florida
Study officials:
References: