Advanced Melanoma
Conditions
Keywords
FANG, Melanoma, Vigil
Brief 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.
Interventions
BIOLOGICALVigil™ Vaccine
Sponsors
Gradalis, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Enzyme-Linked ImmunoSorbent Spot (ELISPOT) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Alive Subjects | 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. |
Countries
United States
Participant flow
Recruitment details
This study recruited patients with Stages IIIc and IV melanoma.
Pre-assignment details
18 were enrolled but 10 screen-failed so only 8 proceeded with the single group assignment (Vigil treatment).
Participants by arm
| Arm | Count |
|---|---|
| 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.
Vigil™ Vaccine | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease Progression | 6 |
| Overall Study | Screen-Failures | 10 |
Baseline characteristics
| Characteristic | Vigil™ Vaccine |
|---|---|
| Age, Customized Age 0-15 Years | 0 Participants |
| Age, Customized Age 16-64 Years | 9 Participants |
| Age, Customized Age 65 and Older Years | 9 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Black/African American | 0 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants |
| Race/Ethnicity, Customized White/Caucasian | 18 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 15 / 18 |
| other Total, other adverse events | 3 / 18 |
| serious Total, serious adverse events | 3 / 18 |
Outcome results
Primary
Enzyme-Linked ImmunoSorbent Spot (ELISPOT)
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).
Time frame: Baseline, End of Treatment (30 days after last dose) up to 12 months
Population: 18 subjects were consented but only 8 subjects were administered Vigil treatment (10 screen-failed). 7 completed treatment (ELISPOT done) while 1 subject died soon after baseline (ELISPOT not done). After 12 months, 7 subjects had positive ELISPOT response. Statistical analysis was not done. This study was terminated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vigil™ Vaccine | Enzyme-Linked ImmunoSorbent Spot (ELISPOT) | ELISPOT Positive After 12 months | 7 Participants |
| Vigil™ Vaccine | Enzyme-Linked ImmunoSorbent Spot (ELISPOT) | ELISPOT Negative After 12 months | 0 Participants |
| Vigil™ Vaccine | Enzyme-Linked ImmunoSorbent Spot (ELISPOT) | Not Done/Died immediately after Baseline | 1 Participants |
| Vigil™ Vaccine | Enzyme-Linked ImmunoSorbent Spot (ELISPOT) | Not Done/Screen-Failed | 10 Participants |
Secondary
Number of Alive Subjects
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.
Time frame: 3 years
Population: 18 subjects were consented but only 8 were administered Vigil treatment (10 screen-failed). These 8 subjects were followed for survival up to 3 years after Vigil treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vigil™ Vaccine | Number of Alive Subjects | Alive Subjects After 3 years | 1 Participants |
| Vigil™ Vaccine | Number of Alive Subjects | Dead Subjects After 3 years | 7 Participants |
| Vigil™ Vaccine | Number of Alive Subjects | Screen-Failed | 10 Participants |