A Study of Recombinant Vaccinia Virus to Treat Malignant Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00429312
Recruitment Status : Completed
First Posted : January 31, 2007
Last Update Posted : January 15, 2015
Information provided by (Responsible Party):
Jennerex Biotherapeutics

January 29, 2007
January 31, 2007
January 15, 2015
March 2007
February 2008   (Final data collection date for primary outcome measure)
Response rate for injected tumor(s) [ Time Frame: Initial response assessment at 6 weeks ]
Response rate for injected tumor(s)
Complete list of historical versions of study NCT00429312 on Archive Site
  • 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 ]
  • Best overall response for entire disease burden (RECIST criteria) [ Time Frame: Initial response assessment after six weeks ]
  • Progression-free survival (PFS) [ Time Frame: Follow-up every three weeks until new therapy or disease progression ]
  • Response rate of non-injected tumor(s) [ Time Frame: Initial response assessment at six weeks ]
  • Safety, as determined by incidence of treatment-related adverse events, serious adverse events (SAEs), and clinically-significant changes from baseline in routine laboratory parameters
  • Best overall response for entire disease burden (RECIST criteria)
  • Progression-free survival (PFS)
  • Response rate of non-injected tumor(s)
Not Provided
Not Provided
A Study of Recombinant Vaccinia Virus to Treat Malignant Melanoma
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
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.

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.

Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Biological: JX-594
Thymidine kinase-deleted vaccinia virus plus GM-CSF
Other Name: JX594
Experimental: Single Arm
Intratumoral injection(s) of Recombinant Vaccinia GM-CSF, JX-594
Intervention: Biological: JX-594
Mastrangelo MJ, Maguire HC Jr, Eisenlohr LC, Laughlin CE, Monken CE, McCue PA, Kovatich AJ, Lattime EC. Intratumoral recombinant GM-CSF-encoding virus as gene therapy in patients with cutaneous melanoma. Cancer Gene Ther. 1999 Sep-Oct;6(5):409-22.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
December 2009
February 2008   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically-confirmed, Stage 3 or Stage 4 malignant melanoma
  • At least one tumor mass measurable by CT/MRI and/or physical examination that can be injected by direct visualization or by ultrasound-guidance
  • Anticipated survival of at least 16 weeks
  • Cancer is not surgically resectable for cure
  • Age ≥18 years
  • Men and women of reproductive potential must be willing to follow accepted birth control methods during treatment and for 3 months after the last treatment with JX-594
  • The ability to understand and willingness to sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent form
  • Able to comply with study procedures and follow-up examinations
  • Adequate liver function: Total bilirubin ≤ 2.0 x ULN; AST, ALT ≤ 2.0 x ULN
  • Adequate bone marrow function: WBC > 3,500 cells/mm3 and < 50,000 cells/mm3; ANC > 1,500 cells/mm3; Hemoglobin > 10 g/dL; Platelet count > 125,000 plts/mm3
  • Acceptable coagulation status: INR < (ULN + 10%)
  • Acceptable kidney function: Serum creatinine < 2.0 mg/dL

Exclusion Criteria:

  • Target tumor(s) adherent to and/or invading a major vascular structure (e.g. carotid artery)
  • Pregnant or nursing an infant
  • Known infection with HIV
  • Systemic corticosteroid or other immunosuppressive medication use within 4 weeks of first treatment with JX-594
  • Clinically significant active infection or uncontrolled medical condition (e.g. pulmonary, neurological, cardiovascular, gastrointestinal, genitourinary) considered high risk for investigational new drug treatment Significant immunodeficiency due to underlying illness and/or medication (e.g. systemic corticosteroids)
  • History of eczema that at some stage has required systemic therapy
  • Clinically significant and/or rapidly accumulating ascites, peri-cardial and/or pleural effusions (e.g. requiring drainage for symptom control)
  • Severe or unstable cardiac disease which includes, but is not limited to, any of the following within 6 months prior to screening: myocardial infarct, unstable angina, congestive heart failure, myocarditis, arrhythmias diagnosed and requiring medication, or any clinically-significant change in cardiac status
  • Treatment of the target tumor(s) with radiotherapy, chemotherapy, surgery, or an investigational drug within 4 weeks of screening (6 weeks in case of mitomycin C or nitrosoureas)
  • Experienced a severe reaction or side-effect as a result of a previous smallpox vaccination
  • Inability or unwillingness to give informed consent or comply with the procedures required in this protocol
  • Patients with household contacts who are pregnant or nursing an infant, children < 5 years old, have history of eczema that at some stage has required systemic therapy, or have a significant immunodeficiency due to underlying illness (e.g. HIV) and/or medication (e.g. systemic corticosteroids) will be excluded unless alternate living arrangements can be made during the patient's active dosing period and for three weeks following the last dose of study medication.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
Not Provided
Jennerex Biotherapeutics
Jennerex Biotherapeutics
Not Provided
Principal Investigator: James Burke, M.D. Billings Clinic
Study Director: David H Kirn, M.D. Jennerex Biotherapeutics
Jennerex Biotherapeutics
March 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP