Phase II FANG™ in Advanced Melanoma
Condition: Advanced Melanoma
MeSH terms: Melanoma
Intervention: Vigil™ Vaccine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: FANG; Melanoma; Vigil

Summary:

      Preliminary studies with a variety of vaccines suggest target accessibility (potential
      immunogenicity) in a variety of solid tumors to immune directed approaches. In an effort to
      overcome limitations of immunostimulatory cancer vaccines, the investigators have designed a
      novel autologous vaccine to address inability to fully identify cancer associated antigens,
      antigen recognition by the immune system (i.e. antigen to immunogen), effector potency, and
      cancer-induced resistance. In an effort to overcome limitations of immunostimulatory cancer
      vaccines, the investigators designed a novel dual-modulatory autologous whole cell vaccine,
      Vigil™ (bi-shRNA furin and GMCSF Autologous Tumor Cell Vaccine), incorporating the rhGMCSF
      (recombinant human GMCSF) transgene and the bifunctional shRNAfurin (to block proprotein
      conversion to active TGFb1 and b2) to 1) address the inability to fully identify cancer
      associated antigens, 2) effect antigen recognition by the immune system (i.e. antigen to
      immunogen), 3) enhance effector potency, and 4) subvert endogenous cancer-induced immune
      resistance. The investigators have also completed the Phase I assessment of Vigil™ vaccine in
      27 advanced solid tumor patients (1.0 x 10e7 or 2.5 x 10e7 cells/injection/month for a
      maximum of 12 vaccinations) who have not experienced any significant adverse effects
      following 131 vaccinations, including 4 patients with melanoma. Plasmid functionality, immune
      biomarker response, and preliminary evidence of anticancer activity have been observed. This
      is a Phase II study of intradermal autologous Vigil™ cancer vaccine (1.0 x 10e7
      cells/injection; maximum of 12 vaccinations) in patients with stages IIIc and IV melanoma
      with biopsy accessible lesions to document blood and intratumoral immune responses and assess
      correlation with survival.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed Stages IIIc and IV melanoma.

          2. Has been informed of all alternative ≥ second-line therapies that are the current
             standard of care. If no conventional frontline therapy indicated or acceptable by
             patient, patient may participate after review by sponsor.

          3. Clinically (medically) indicated procedure (i.e. biopsy of lesions of recurrent
             disease, palliative management via resection, thoracentesis, etc.) to collect viable
             tumor in sufficient quantity ("golf ball size" estimated weight ~ 30 grams, pleural
             and/or ascites fluid estimated volume ≥ 500mL) for vaccine processing.

          4. Recovered to ≤ Grade 1 (excluding alopecia) from all clinically relevant toxicities
             related to prior therapies.

          5. Patients will be allowed to participate following single prior CNS treatment with
             stereotactic radiotherapy whole brain irradiation and stable without steroid
             requirement for ≥2 months or following ≥2 prior CNS treatments with stereotactic
             radiotherapy whole brain irradiation and stable without steroid requirement for ≥4
             months.

          6. Patients must be off all "statin" drugs for ≥ 2 weeks prior to initiation of therapy.

          7. Age ≥18 years.

          8. ECOG performance status (PS) 0-1.

          9. Estimated >4 month survival probability.

         10. Normal organ and marrow function as defined below:

             Absolute granulocyte count ≥1,500/mm3 Absolute lymphocyte count ≥500/mm3 Platelets
             ≥100,000/mm3 Total bilirubin ≤2 mg/dL AST(SGOT)/ALT(SGPT) ≤2x institutional upper
             limit of normal Creatinine <1.5 mg/dL

         11. Ability to understand and the willingness to sign a written informed consent document.

         12. Negative pregnancy test.

        Exclusion Criteria:

          1. Surgery involving general anesthesia, chemotherapy, radiotherapy, steroid therapy, or
             immunotherapy within 4 weeks prior to entering the study. Collection of lumenal tissue
             must be avoided.

          2. Patient must not have received any other investigational agents within 30 days prior
             to study entry.

          3. Patients with known active or symptomatic brain metastases.

          4. Patients with compromised pulmonary disease.

          5. Short term (<30 days) concurrent systemic steroids ≤ 0.25 mg/kg prednisone per day
             (maximum 7.5 mg/day) and bronchodilators (inhaled steroids) are permitted; other
             steroid regimens and/or immunosuppressives are excluded. Patients requiring steroids
             following previous CNS radiation for metastatic disease are excluded.

          6. Prior splenectomy.

          7. Prior malignancy (excluding nonmelanoma carcinomas of the skin) unless in remission
             for 2 years.

          8. Kaposi's Sarcoma.

          9. Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

         10. Patients who are pregnant or nursing.

         11. Patients with known HIV.

         12. Patients with chronic Hepatitis B and C infection.

         13. Patients with uncontrolled autoimmune diseases.