Clinical Trials /

Intratumoral Gene Mediated Cytotoxic Immunotherapy in Patients With Resectable Non-Small Cell Lung Cancer

NCT03131037

Description:

This is a phase I study of Gene Mediated Cytotoxic Immunotherapy (GMCI) in patients with non-small cell lung cancer (NSCLC). The primary clinical end-point of the study is to evaluate the safety of GMCI when combined with standard surgery for NSCLC. The primary scientific objective is to determine the immunologic changes induced by GMCI.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Intratumoral Gene Mediated Cytotoxic Immunotherapy in Patients With Resectable Non-Small Cell Lung Cancer
  • Official Title: Intratumoral Gene Mediated Cytotoxic Immunotherapy (GMCI) For Resectable Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: LuTK01
  • NCT ID: NCT03131037

Conditions

  • Lung Cancer

Interventions

DrugSynonymsArms
AdV-tk (aglatimagene besadenovec) + valacyclovirStudy Arm

Purpose

This is a phase I study of Gene Mediated Cytotoxic Immunotherapy (GMCI) in patients with non-small cell lung cancer (NSCLC). The primary clinical end-point of the study is to evaluate the safety of GMCI when combined with standard surgery for NSCLC. The primary scientific objective is to determine the immunologic changes induced by GMCI.

Detailed Description

      The purpose of this open-label, dose escalation clinical trial is to investigate the safety
      of GMCI prior to surgery in patients with NSCLC. GMCI involves the use of aglatimagene
      besadenovec (AdV-tk) injected into the tumor followed by oral valacyclovir prodrug to kill
      tumor cells and stimulate a cancer vaccine effect. Killing tumor cells in an immune
      stimulatory environment induces the body's immune system to detect and destroy cancer cells.
      GMCI has been well tolerated in previous trials in multiple tumor types with clinical,
      pathologic and immune responses.

      AdV-tk will be injected intratumorally on day 0 during a standard of care staging procedure.
      The prodrug, valacyclovir, will be administered orally at a fixed dose for 14 days following
      the AdV-tk injection. Then standard of care surgical resection will be performed about 3
      weeks after the AdV-tk injection. Chemotherapy and/or radiation may begin 6-8 weeks after
      resection surgery. Choice of chemotherapy depends on the treating oncologist.
    

Trial Arms

NameTypeDescriptionInterventions
Study ArmExperimentalAdV-tk (aglatimagene besadenovec) + valacyclovir
  • AdV-tk (aglatimagene besadenovec) + valacyclovir

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically documented non-small cell carcinoma (cytology or histology) that is
             accessible via standard-of-care staging procedures: (1) EBUS or (2) surgical
             approaches (eg mediastinoscopy, mediastinotomy or VATS).

          -  Resectable with negative lymph nodes based on imaging with histologic confirmation at
             time of the staging procedure prior to AdV-tk injection

          -  The tumor must be 4cm or greater in diameter based on imaging

          -  ECOG Performance status of 0 or 1.

          -  Granulocyte count (ANC) ≥ 1,000/mm3

          -  Peripheral lymphocyte count ≥ 500/mm3

          -  Hemoglobin ≥ 9 g/dl

          -  Platelets ≥ 100,000/mm3

          -  Total bilirubin ≤ 1.5 x upper limit of normal

          -  SGOT (AST) ≤ 3x upper limit of normal

          -  Serum creatinine < 2mg/dl

          -  Calculated creatinine clearance > 30ml/min

          -  Patients must give study specific informed consent prior to enrollment

        Exclusion Criteria:

          -  Radiotherapy and/or treatment with chemotherapeutic, cytotoxic, or immunologic agents
             within 4 weeks prior to infusion of the vector.

          -  Known immunodeficiency such as HIV infection

          -  Active liver disease, including known cirrhosis or active hepatitis

          -  Use of systemic corticosteroids (>10 mg prednisone per day or equivalent) or other
             systemic immunosuppressive drugs

          -  Patient is pregnant or breast-feeding. Female patients of childbearing age must have
             negative serum or urine pregnancy test within 1 week of beginning therapy. Subjects
             must use acceptable means of birth control until 30 days after the vector injection.

          -  Presence of any other life-threatening illness, such as unstable angina, severe oxygen
             dependence, significant chronic obstructive pulmonary disease (COPD), end-stage liver
             or renal disease. COPD will be considered significant if disease limits activities of
             daily living, results in the inability to walk up 1 flight of stair, or requires home
             oxygen.

          -  Presence of known untreated brain metastases.

          -  Prior bone marrow transplants (including stem cells) except autologous stem cell
             transplant without immunosuppression is NOT considered an exclusion.

          -  Known sensitivity or allergic reactions to valacyclovir
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety
Time Frame:6 weeks
Safety Issue:
Description:Safety based on standard laboratory and clinical adverse event monitoring.

Secondary Outcome Measures

Measure:Immunologic changes
Time Frame:12 months
Safety Issue:
Description:The effect of GMCI on the histology and immune profile of the resected tumor. Systemic and intratumoral cytokine responses will also be assessed.
Measure:Progression free survival (PFS)
Time Frame:5 years
Safety Issue:
Description:The PFS curves will be estimated using the Kaplan-Meier method.
Measure:Overall survival (OS)
Time Frame:5 years
Safety Issue:
Description:The OS curves will be estimated using the Kaplan-Meier method.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Advantagene, Inc.

Trial Keywords

  • immunotherapy
  • immuno-oncology
  • tumor vaccine

Last Updated

June 28, 2019