Clinical Trials /

GL-ONC1 Oncolytic Immunotherapy in Patients With Recurrent or Refractory Ovarian Cancer

NCT02759588

Description:

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.

Related Conditions:
  • Ovarian Carcinoma
  • Ovarian Carcinosarcoma
  • Ovarian Clear Cell Adenocarcinofibroma
  • Ovarian Endometrioid Tumor
  • Ovarian Serous Adenocarcinoma
  • Peritoneal Carcinomatosis
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: GL-ONC1-015
  • NCT ID: NCT02759588

Conditions

  • Ovarian Cancer
  • Peritoneal Carcinomatosis
  • Fallopian Tube Cancer

Interventions

DrugSynonymsArms
GL-ONC1 alone, or in combination with chemotherapy with or without bevacizumabGL-ONC1

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
GL-ONC1Experimental
  • GL-ONC1 alone, or in combination with chemotherapy with or without bevacizumab

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:21 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-emergent Adverse Events [Safety and Tolerability] (Phase 1b)
Time Frame:Change from baseline during Treatment and for 30 days following last dose.
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Evaluation of Tumor Response to Treatment (Phase 1b)
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.
Safety Issue:
Description: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).
Measure:Evaluation of Immune-related Tumor Response
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.
Safety Issue:
Description: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).
Measure:CA-125 Response (Phase 1b)
Time Frame:Assessed pre-treatment, during treatment and post-treatment at 6 to 12 week intervals, assessed up to 24 months.
Safety Issue:
Description: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.
Measure:Determine Progression-free Survival following Treatment (Phase 1b)
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.
Safety Issue:
Description:To assess progression-free survival (PFS) in participant population.
Measure:Overall Survival
Time Frame:By medical chart review until death or 3 years from the date of last treatment which ever comes first.
Safety Issue:
Description:To determine overall survival (OS) in the participant population.
Measure:Clinical Benefit Rate
Time Frame:Approximately 24 months
Safety Issue:
Description:Defined as the percentage of patients who have achieved CR + PR + SD greater than or equal to 15 weeks.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Genelux Corporation

Trial 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

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