Vaccine Treatment for Advanced Non-Small Cell Lung Cancer
Condition: Non-small Cell Carcinoma; Adenocarcinoma of Lung; Squamous Cell Carcinoma; Large Cell Carcinoma; Lung Neoplasms
MeSH terms: Carcinoma; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung; Carcinoma, Large Cell
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This 2-phase study will determine the safety of treating patients with non-small cell lung
      cancer with the genetically engineered HyperAcute-Lung cancer vaccine. It will establish the
      proper vaccine dose and will examine side effects and potential benefits of the treatment.
      The vaccine contains killed lung cancer cells containing a mouse gene that causes the
      production of a foreign pattern of protein-sugars on the cell surface. It is hoped that the
      immune response to the foreign substance will stimulate the immune system to attack the
      patient's own cancer cells that have similar proteins without this sugar pattern, causing the
      tumor to remain stable or shrink.

      Patients 18 years of age or older with non-small cell lung cancer that has recurred or no
      longer responds to standard treatment may be eligible for this study. Candidates will be
      screened with a medical history and physical examination, blood tests, urinalysis, chest
      x-rays, and lung function testing. CT, MRI, PET, and ultrasound scans of the chest may be
      obtained if needed.

      Participants will receive four vaccinations a month apart from each other. The vaccines will
      be injected under the skin, similar to the way a tuberculosis skin test is given. Phase I of
      the study will treat successive groups of patients with increasing numbers of the vaccine
      cells to evaluate side effects of the treatment and determine the optimum dose. Phase II will
      look for any beneficial effects of the vaccine given at the highest dose found to be safe in
      Phase I. Weekly blood samples will be drawn during the 4 months of vaccine treatment. In
      addition, patient follow-up visits will be scheduled every 2 months for the first year after
      vaccination and then every 3 months for the next 2 years for the following tests and
      procedures to evaluate treatment response and side effects:

        -  Medical history and physical examination

        -  Blood tests

        -  X-rays and various scans (nuclear medicine/CT/MRI)

        -  FACT-L Assessment questionnaire to measure the impact of treatment on the patient's
           general well-being. The questionnaire is administered before beginning treatment, before
           each vaccination, and during follow-up visits after completing the treatment. It
           includes questions on the severity of lung cancer symptoms and the ability to perform
           normal activities of daily life.

      In addition to the above procedures, 3 skin punch biopsies will be done at the vaccination
      site to look for a local immune response. For this procedure, an area of skin is numbed with
      an anesthetic and a 4 mm (about 1/4-inch) circular area is removed, using a sharp cookie
      cutter-type instrument. Also, one blood sample per year will be collected for the next 15
      years to monitor the safety of the gene transfer. Patients whose lung cancer spreads to the
      skin, superficial soft tissues, or a superficial lymph node may be asked to undergo a biopsy
      of the lesion to see what effect the treatment may be having on the tumor.
    

Detailed description: 
      Background:

        -  Lung cancer remains the leading cause of cancer death with an estimated 174,400 new
           cases and 162,400 deaths each year in the U.S.

        -  Despite attempts at early diagnosis and the development of new therapeutic agents, there
           has been only limited improvement in the outcome for patients with advanced lung cancer.

        -  A enzyme called alpha(1,3)galactosyltranferase (alphaGT) that is not found in humans can
           transfer sugars on to proteins in human cells that can make them highly immunogenic and
           cause them to be rejected by the body.

        -  Antitumor vaccination using killed donor human lung cancer cells expressing alphaGT may
           stimulate immune responses in patients against their own lung cancer because their lung
           cancer may share antigens with the vaccine cells that have been made more immunogenic by
           expression of alphaGT.

      Objectives:

      Phase I has been completed.

      Phase II

        -  To assess the tumor response rate of anti-tumor vaccination using irradiated allogeneic
           lung cancer cell lines genetically engineered to express the murine
           alpha(1,3)galactosyltransferase enzyme in patients with advanced, recurrent or
           refractory non-small cell lung cancer.

        -  To assess the immunological response of patients with lung cancer undergoing antitumor
           vaccination with irradiated allogeneic lung cancer cell lines genetically engineered to
           express murine alpha(1,3)galactosyltransferase.

        -  Assess the survival distribution as well as the duration of response.

      Eligibility:

        -  Non-small cell lung cancer (Adenocarcinoma, squamous cell carcinoma, large cell
           anaplastic carcinoma and bronchoalveolar carcinoma).

        -  Stage IV, recurrent or treatment refractory disease.

        -  No exclusion for prior therapy. Prior therapy may include surgery, radiation,
           immunotherapy, and chemotherapy regimens. EGFR inhibitors or monoclonal antibodies are
           included as chemotherapy.

        -  Patients must have a granulocyte count of greater than or equal to 1000/microL,
           platelets greater than or equal to 100,000/microL, hemoglobin greater than 10.0 gm/dL,
           albumin greater than or equal to 3.0 gm/dL and acceptable hepatic and renal function.

        -  No systemic corticosteroids.

      Design (Phase II):

        -  Patients will be intradermally vaccinated with 300 million
           alpha(1,3)galactosyltranferase-expressing vaccine cells every 2-weeks to complete a
           total of eight vaccinations.

        -  Patients will be monitored for tumor and immunological responses and safety.
    

Intervention name(s): Drug: Hyperacute Lung Cancer Cell Vaccine
Intervention type(s): Biological
Intervention description(s): At dose levels I IV the vaccine cells will be injected intradermally every four weeks for four cycles. Dosage will vary from a total of 3 x 106 to 100 x 106 HyperAcute -Lung Cancer Vaccine cells administered per vaccination cycle. At dose level V patients will receive injections of the HyperAcute -Lung Cancer Vaccine cells to include one (1) initial priming vaccine dose of 500 x 106 cells followed by seven (7) booster vaccine cell doses of 300 x 106 HyperAcute -Lung Cancer cell vaccine cells every two weeks. In Phase II, patients will receive 300 x 106 HyperAcute -Lung Cancer cell vaccine cells every two weeks for a total of 8 doses (4 months).
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Anti-tumor Vaccination; Alpha (1,3) Galactosyltransferase; Allogeneic Tumor Cells; Hyperacute Lung; NSCLC; Lung Cancer; Non-Small Cell Lung Cancer