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Phase II FANG in Advanced Melanoma

This study is currently recruiting participants.
Verified April 2013 by Gradalis, Inc.
Sponsor:
Information provided by (Responsible Party):
Gradalis, Inc.
ClinicalTrials.gov Identifier:
NCT01453361
First received: August 10, 2011
Last updated: April 5, 2013
Last verified: April 2013
History of Changes
  Purpose

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, FANG™ (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 FANG 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 FANG 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: FANG™ Autologous Tumor Cell Vaccine in Advanced Melanoma
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel 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:

MedlinePlus related topics: Cancer Melanoma
U.S. FDA Resources

Further study details as provided by Gradalis, Inc.:

Primary Outcome Measures:
  • Immune Responses to FANG [ 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 FANG™ 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 FANG™ vaccine and compare with historical data. Participants will be followed for life.


Estimated Enrollment: 15
Study Start Date: October 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1.0 x 10e7 cells/injection/month Biological: FANG™ Autologous Tumor Cell Vaccine in Advanced Melanoma
Autologous FANG™ 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.
Experimental: 2.5 x 10e7 cells/injection/month Biological: FANG™ Autologous Tumor Cell Vaccine in Advanced Melanoma
Autologous FANG™ 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.

Detailed Description:

This is a Phase I open-label trial of FANG autologous tumor cell vaccine in inpatients with stages IIIc and IV melanoma. Patients will receive FANG™ autologous tumor vaccine once every 4 weeks for up to 12 doses via intradermal injection as long as sufficient material is available. All patients with successful harvest for a minimum of 5 (1 x 10e7 cells / injection) monthly injections will be entered into the study. Patients in whom insufficient tissue (<5 doses) is collected or whose vaccine fails manufacturing release criteria will not receive vaccine. The patients will be managed in an outpatient setting. Hematologic function, liver enzymes, renal function and electrolytes will be monitored by once weekly assessment during Cycle 1. Immune response (defined as production of interferon-gamma and granzyme from CD8+ T cells in response to autologous tumor antigens as evaluated in the ELISPOT assay) and secondary immunologic endpoints including, but not limited to, PBMC counts, phenotyping of blood lymphocyte subsets (T cell subsets including CD4, CD8 and Treg cells, NK cells, etc), and Fox P3+ cells will be monitored at baseline, months 2, 3, 4, end of treatment, and at response follow up visits. (Note that in some instances IFN secretion and granule exocytosis are uncoupled. Therefore the direct measurement of granzyme B (gzB) secretion by ELISPOT provides a more direct readout for antigen-specific granule exocytosis and cytotoxicity. For clinical efficiency it may be important to detect both IFN-gamma secretion and gzB exocytosis.) Intratumoral immune response including CD4, CD8 and Treg cells, NK cells, MHC I, MHC II, and Fox P3+ cells will be monitored at baseline and at month 2 and month 4. If tissue is available, biopsy one month following end of treatment or at progression will be likewise be obtained for immune phenotype analysis.

Treatment will be continued until progressive disease however, insofar as some patients in our early vaccine trials had increased survival despite initial tumor progression, if early progression is noted without clinically significant symptomatic change, particularly at the 2 month evaluation, patient will continue on protocol after review with the PI. Each investigator will assess disease response (complete response [irCR], partial response [irPR], stable disease [irSD], and progressive disease [irPD]) using IRC criteria (Wolchok, Hoos et al. 2009) as well as RECIST criteria for measurable/detectable disease. If ≥ Grade 2 toxicity by NCI Common Toxicity Criteria (excluding Grade 2 fever less than 24 hours and Grade 3 injection site reaction) develops related to study treatment the vaccine dose will be reduced by 50% and continued on a monthly basis.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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. Biopsy accessible lesion.
  5. Recovered to ≤ grade 1 (excluding alopecia) from all clinically relevant toxicities related to prior therapies.
  6. 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.
  7. Patients must be off all "statin" drugs for ≥ 2 weeks prior to initiation of therapy.
  8. Age ≥18 years.
  9. ECOG performance status (PS) 0-1.
  10. Estimated >4 month survival probability.

  11. 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

  12. Ability to understand and the willingness to sign a written informed consent document.
  13. 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 ≤ 0.125 mg/kg prednisone per day (maximum 10 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 (see inclusion criteria 5).
  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. Patient with known HIV.
  11. Patient with chronic Hepatitis B and C infection.
  12. Patients with uncontrolled autoimmune diseases.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01453361

Contacts
Contact: Meghan Degele 972-566-3062 mdegele@marycrowley.org
Contact: Rachel Marshall 972-566-3061 rmarshall@marycrowley.org

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

Publications:

Responsible Party: Gradalis, Inc.
ClinicalTrials.gov Identifier: NCT01453361     History of Changes
Other Study ID Numbers: CL-PTL 114
Study First Received: August 10, 2011
Last Updated: April 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Gradalis, Inc.:
FANG
Melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
 Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on May 21, 2013