NY-ESO-1 Protein With Montanide and CpG 7909 as Cancer Vaccine in Several Tumors
Condition: Tumors
Intervention: NY-ESO-1 Protein Vaccine
Intervention description: NY-ESO-1 recombinant protein mixed with CpG 7909 and Montanide ISA-51 VG
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NY-ESO-1; Vaccine; Adjuvant or metastatic setting; Several tumor types eligible

Summary:

      This is a Phase I, open-label, randomized study of NY-ESO-l protein with immune adjuvants CpG
      7909 and Montanide ISA-51 VG in patients with tumors that often express NY-ESO-1.

      The vaccinations was to be administered subcutaneously every 3 weeks for 4 doses.

      Patients with any malignancy that is known to frequently express NY-ESO-1 were eligible,
      regardless of whether antigen expression in the autologous tumor could be demonstrated or not
      by either PCR or immunohistochemistry.

      The primary objective of the study was to define safety.

      Secondarily, the study was to evaluate whether patients developed a specific immunologic
      response to the NY-ESO-1 protein. Blood samples were to be obtained at baseline, prior to
      each vaccination, one week after each vaccination, and at the last study visit for the
      assessment of NY-ESO-1-specific CD4+ and CD8+ T cells. Cytokine secretion by
      NY-ESO-1-specific CD8+ and CD4+ T cells, as a measure of T cell activation, was to be
      determined by FACS analysis. In addition, humoral immunity was to be determined by the
      presence of NY-ESO-1-specific antibodies which were to be assessed in all patients by ELISA.

      Disease status was to be assessed at baseline and 2-4 weeks after the fourth vaccination in
      patients with evaluable (measurable and non-measurable) disease.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histological diagnosis of hepatocellular carcinoma, bladder cancer, breast cancer,
             non-small lung cancer (NSCLC), melanoma, sarcoma, prostate cancer, esophageal cancer,
             or ovarian cancer, independent of NY-ESO-1 expression in a tumor biopsy.

             or

             Histological diagnosis of other types of cancers, provided NY-ESO-1 or LAGE-1
             expression can be shown in a tumor biopsy.

          2. At least 4 weeks since surgery prior to first dosing of study agent.

          3. Laboratory values within the following limits:

               -  Hemoglobin ≥ 11.0 g/dL

               -  Neutrophil count ≥ 1.5 x l0^9/L

               -  Lymphocyte count ≥ lower limit of institutional normal

               -  Platelet count ≥ 80 x l0^9/L

               -  Serum creatinine ≤ 2.0 mg/dL

               -  Serum bilirubin ≤ 2 x upper limit of institutional normal

               -  AST/ALT ≤ 2 x upper limit of institutional normal

          4. Patients must have a Karnofsky performance status of ≥70%.

          5. Life expectancy ≥ 6 months.

          6. Age ≥ 18 years.

          7. Able and willing to give witnessed, written informed consent for participation in the
             trial.

        Exclusion Criteria:

          1. Clinically significant heart disease (i.e. NYHA class 3 congestive heart failure;
             myocardial infarction within the past six months; unstable angina; coronary
             angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac
             arrhythmias).

          2. Other serious illnesses, eg, serious infections requiring antibiotics, bleeding
             disorders.

          3. Previous bone marrow or stem cell transplant.

          4. History of immunodeficiency disease or autoimmune disease except vitiligo.

          5. Metastatic disease to the central nervous system, unless treated and stable.

          6. Other malignancy within 3 years prior to entry into the study, except for treated
             early-stage melanoma or non-melanoma skin cancer, or cervical carcinoma in situ.

          7. Known HIV, Hepatitis B or Hepatitis C positivity.

          8. Chemotherapy, radiation therapy or immunotherapy within 4 weeks prior to first dose of
             study agent (6 weeks for nitrosoureas).

          9. Concomitant treatment with steroids. Topical or inhalational steroids are permitted.

         10. Participation in any other clinical trial involving another investigational agent
             within 4 weeks prior to first dose of study agent.

         11. Pregnancy or lactation.

         12. Women of childbearing potential not using a medically acceptable means of
             contraception.

         13. Psychiatric or addictive disorders that may compromise the ability to give informed
             consent.

         14. Lack of availability of the patient for immunological and clinical follow-up
             assessment.