Phase II FANG™ in Advanced Melanoma

May 21, 2018 updated by: Gradalis, Inc.

Phase II Trial of FANG™ Autologous Tumor Cell Vaccine in Advanced Melanoma

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Dallas, Texas, United States, 75230
        • Mary Crowley Cancer Research Centers

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • formerly known as FANG™

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Enzyme-Linked ImmunoSorbent Spot (ELISPOT)
Time Frame: Baseline, End of Treatment (30 days after last dose) up to 12 months
To determine if subjects will have a positive (defined as >10 ELISPOTS from baseline) immune response to Vigil. Blood was collected to compare ELISPOT results from baseline until EOT (30 days after last dose).
Baseline, End of Treatment (30 days after last dose) up to 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Alive Subjects
Time Frame: 3 years
The survival status in patients with stages IIIc and IV melanoma treated with Vigil™ vaccine was determined by following these patients up to 3 years.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gradalis, Inc.

Investigators

  • Principal Investigator: Minal Barve, MD, Mary Crowley Cancer Research Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2011

Primary Completion (Actual)

March 22, 2016

Study Completion (Actual)

March 22, 2016

Study Registration Dates

First Submitted

August 10, 2011

First Submitted That Met QC Criteria

October 14, 2011

First Posted (Estimate)

October 17, 2011

Study Record Updates

Last Update Posted (Actual)

May 24, 2018

Last Update Submitted That Met QC Criteria

May 21, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CL-PTL 114

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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