A Study of Recombinant Vaccinia Virus to Treat Malignant Melanoma
The purpose of this research study is to find out whether JX-594 (Pexa-Vec) is safe and effective for treating surgically unresectable malignant melanoma.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II, Open-Label Study of JX-594 (Thymidine Kinase-deleted Vaccinia Virus Plus GM-CSF) Administered by Intratumoral Injection in Patients With Unresectable Stage 3 or Stage 4 Malignant Melanoma|
- Response rate for injected tumor(s) [ Time Frame: Initial response assessment at 6 weeks ] [ Designated as safety issue: No ]
- Safety, as determined by incidence of treatment-related adverse events, serious adverse events (SAEs), and clinically-significant changes from baseline in routine laboratory parameters [ Time Frame: Safety evaluation throughout study period ] [ Designated as safety issue: Yes ]
- Best overall response for entire disease burden (RECIST criteria) [ Time Frame: Initial response assessment after six weeks ] [ Designated as safety issue: No ]
- Progression-free survival (PFS) [ Time Frame: Follow-up every three weeks until new therapy or disease progression ] [ Designated as safety issue: No ]
- Response rate of non-injected tumor(s) [ Time Frame: Initial response assessment at six weeks ] [ Designated as safety issue: No ]
|Study Start Date:||March 2007|
|Study Completion Date:||December 2009|
|Primary Completion Date:||February 2008 (Final data collection date for primary outcome measure)|
Cancer of the skin is the most common of all cancers, probably accounting for more than 50% of all cancers. Melanoma accounts for about 4% of skin cancer cases but causes a large majority of skin cancer deaths. The American Cancer Society estimates that about 62,190 new melanomas will be diagnosed in the United States during 2006.
DTIC is the only chemotherapy drug approved by the FDA for the treatment of metastatic melanoma. The reported response rates are 5-20% without any evidence of prolonged survival in randomized clinical trials versus best supportive care. The median overall survival for melanoma patients treated with DTIC alone is approximately 8 months; PFS and TTP following treatment with DTIC is approximately 7 weeks, and the objective response rate for DTIC alone (CR+PR) is less than 10% (Millward, 2004). Other chemotherapy agents including cisplatin and carboplatin, BCNU, vindesine, paclitaxel, docetaxel, and vinorelbine have also been tested but none have improved upon the very modest activity of DTIC.
Melanoma may be the optimal target for JX-594 immunotherapy because of the relatively high rate of accessible disease for injection, the positive response of melanoma seen with IL-2 immunotherapy, and the lack of effective, tolerable therapy for patient with metastatic melanoma. Furthermore, it is speculated that JX-594 replication targets the EGFR pathway, which is highly expressed in melanocytes.
Results from an initial Phase I/II study suggest that intratumoral injection of JX-594 is safe and effective in treating both injected and distant disease in patients with surgically incurable metastatic melanoma. Response of both injected tumors (in 5 of 7 patients) and response of at least one non-injected tumor (in 4 of 7 patients) was demonstrated, including two patients who achieved a partial response (6 + months) and a complete response (4 + months) to JX-594 treatment. Particularly noteworthy is that efficacy and gene expression occurred despite pre-treatment vaccination (and, therefore, pre-existing anti-vaccinia immunity) in all patients.
|United States, California|
|Los Angeles, California, United States, 90095|
|United States, Montana|
|Billings, Montana, United States, 59101|
|United States, South Carolina|
|Cancer Center of the Carolinas|
|Greenville, South Carolina, United States, 29605|
|Principal Investigator:||James Burke, M.D.||Billings Clinic|
|Study Director:||David H Kirn, M.D.||Jennerex Biotherapeutics|