A Study of Recombinant Vaccinia Virus to Treat Malignant Melanoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jennerex Biotherapeutics
ClinicalTrials.gov Identifier:
NCT00429312
First received: January 29, 2007
Last updated: April 1, 2013
Last verified: March 2010
  Purpose

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.


Condition Intervention Phase
Melanoma
Biological: JX-594
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Jennerex Biotherapeutics:

Primary Outcome Measures:
  • Response rate for injected tumor(s) [ Time Frame: Initial response assessment at 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 10
Study Start Date: March 2007
Study Completion Date: December 2009
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: JX-594
    Thymidine kinase-deleted vaccinia virus plus GM-CSF
    Other Name: JX594
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  • KPS score of ≥ 70 (refer to APPENDIX E: KARNOFSKY PERFORMANCE STATUS (KPS))
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00429312

Locations
United States, California
UCLA
Los Angeles, California, United States, 90095
United States, Montana
Billings Clinic
Billings, Montana, United States, 59101
United States, South Carolina
Cancer Center of the Carolinas
Greenville, South Carolina, United States, 29605
Sponsors and Collaborators
Jennerex Biotherapeutics
Investigators
Principal Investigator: James Burke, M.D. Billings Clinic
Study Director: David H Kirn, M.D. Jennerex Biotherapeutics
  More Information

Publications:
Responsible Party: Jennerex Biotherapeutics
ClinicalTrials.gov Identifier: NCT00429312     History of Changes
Other Study ID Numbers: JX594-IT-MEL005
Study First Received: January 29, 2007
Last Updated: April 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Jennerex Biotherapeutics:
Melanoma
Oncolytic virus
Pexa-Vec

Additional relevant MeSH terms:
Melanoma
Vaccinia
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Poxviridae Infections
DNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on August 28, 2014