Phase II Trial of FANG™ Autologous Tumor Cell Vaccine in Advanced Melanoma
18 Years
N/A
Both
Advanced Melanoma
Trial Information
Phase II Trial of FANG™ Autologous Tumor Cell Vaccine in Advanced Melanoma
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.
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.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Immune Responses to FANG
Outcome Description:
To evaluate and correlate blood and intratumoral immune responses to FANG™ vaccine in patients with melanoma.
Outcome Time Frame:
Actively monitored for one year then quarterly for 3 years
Safety Issue:
No
Principal Investigator
Minal Barve, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mary Crowley Cancer Research Center
Authority:
United States: Food and Drug Administration
Study ID:
CL-PTL 114
NCT ID:
NCT01453361
Start Date:
October 2011
Completion Date:
December 2013
Related Keywords:
- Advanced Melanoma
- FANG
- Melanoma
- Melanoma
Name | Location |
|---|---|
| Mary Crowley Cancer Research Centers | Dallas, Texas 75201 |
