Phase II FANG™ in Advanced Melanoma

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Gradalis, Inc. Identifier:
First received: August 10, 2011
Last updated: November 10, 2015
Last verified: November 2015
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.

Condition Intervention Phase
Advanced Melanoma
Biological: Vigil™ Vaccine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of FANG™ Autologous Tumor Cell Vaccine in Advanced Melanoma

Resource links provided by NLM:

Further study details as provided by Gradalis, Inc.:

Primary Outcome Measures:
  • Immune Responses to Vigil™ [ Time Frame: Actively monitored for one year then quarterly for 3 years ] [ Designated as safety issue: No ]
    To evaluate and correlate blood and intratumoral immune responses to Vigil™ vaccine in patients with melanoma.

Secondary Outcome Measures:
  • Survival [ Time Frame: Every 3 months till patients expire ] [ Designated as safety issue: No ]
    To determine the survival in patients with stages IIIc and IV melanoma treated with Vigil™ vaccine and compare with historical data. Participants will be followed for life.

Enrollment: 18
Study Start Date: October 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vigil™ Vaccine
Autologous Vigil™ vaccine will be supplied by Gradalis, Inc. Patients will receive 1 x 10e7 cells via intradermal injection one day each month for a minimum maximum of 12 doses as long as subject is clinically stable.
Biological: Vigil™ Vaccine
Other Name: formerly known as FANG™


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01453361

United States, Texas
Mary Crowley Cancer Research Centers
Dallas, Texas, United States, 75230
Sponsors and Collaborators
Gradalis, Inc.
Principal Investigator: Minal Barve, MD Mary Crowley Cancer Research Center
  More Information

Responsible Party: Gradalis, Inc. Identifier: NCT01453361     History of Changes
Other Study ID Numbers: CL-PTL 114
Study First Received: August 10, 2011
Last Updated: November 10, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Gradalis, Inc.:

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas processed this record on December 01, 2015