MelanomaPhase 1/2NCT00429312
A Study of Recombinant Vaccinia Virus to Treat Malignant Melanoma
A Phase 1/2 study testing JX-594 in people with Melanoma, run by Jennerex Biotherapeutics at 3 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- JX-594
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2007to Dec 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Billings Clinic
Billings, Montana, 59101
Cancer Centers of the Carolinas
Greenville, South Carolina, 29605
University of California, Los Angeles
Los Angeles, California, 90024
About this study
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
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.
Read the 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.
- Conditions
- Melanoma
- Being tested
- JX-594
- Keywords
- Melanoma, Oncolytic virus, Pexa-Vec
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JX-594Biological
Also called Pexa-Vec
Thymidine kinase-inactivated vaccinia virus expressing human GM-CSF
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Intratumoral injection(s) of Recombinant Vaccinia virus JX-594 Receives: Biological: JX-594 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Objective Response in Injected Tumor(s)
Response was evaluated at the participant level based on the sum of the longest diameters of the injected target tumors. Tumor assessments were performed using RECIST criteria. Complete response (CR): all lesions disappear; Partial response (PR): maximum diameter decrease of > 30% of the longest diameter (LD) of target lesions using the baseline LD; Progressive disease (PD): increase of >20% in the sum of LD target lesions using the smallest sum LD recorded since treatment started; Stable disease (SD): unable to categorize as PR or PD using as reference the lobe with the smallest diameter at baseline.
Measured: Initial response assessment after six weeks (Day 43)
Secondary outcomes (4)
Incidence of Treatment-related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Safety was determined by the incidence of treatment-related adverse events (AEs), treatment-related serious adverse events (SAEs), and clinically-significant changes from baseline in routine laboratory parameters. Severity was determined by NCI-CTCAE version 3.0.
Measured: Up to Day 64
Best Overall Response for Entire Disease Burden (RECIST Criteria)
Overall response was defined as the best response recorded from the start of the treatment until disease progression or recurrence across the entire disease burden (both injected and non-injected tumors), evaluated using RECIST criteria (Complete Response [CR], Partial Response [PR], Stable Disease [SD], or Progressive Disease [PD]).
Measured: Initial response assessment after six weeks (Day 43)
Progression-free Survival
Progression-free survival was defined as the time from the first study treatment until objective evidence of disease progression or death.
Measured: From first study treatment until objective evidence of disease progression or death, up to 20.5 months
Number of Participants With Objective Response in Non-injected Tumor(s)
Response was evaluated at the participant level for non-injected tumors.Response rate was evaluated specifically in non-injected tumors to assess systemic anti-tumoral efficacy, evaluated using RECIST criteria (Complete Response [CR], Partial Response [PR], Stable Disease [SD], or Progressive Disease [PD]).
Measured: Initial response assessment after six weeks (Day 43)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2007 (estimated)
- Study startFeb 2007
- Primary completionFeb 2008
- Study completionDec 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jennerex Biotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- James Burke, M.D., Principal investigator, Billings ClinicDavid H Kirn, M.D., Study director, Jennerex Biotherapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00429312
- Sponsor's protocol ID
- JX594-IT-MEL005
- Status last verified
- Jul 2026
- First submitted
- 29 Jan 2007
- Last updated
- 27 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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. doi: 10.1038/sj.cgt.7700066.
PubMed 10505851
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00429312
- Acronym / sponsor ID
- JX594-IT-MEL005
- Conditions
- Melanoma
- Keywords
- Melanoma, Oncolytic virus, Pexa-Vec
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Jennerex BiotherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Feb 2007
- Primary completion
- Feb 2008 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 31 Jan 2007 (estimated)
- Results
- Posted 27 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Biological: JX-594Intratumoral injection(s) of Recombinant Vaccinia virus JX-594 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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))
Key exclusion criteria (12 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JX-594Also: Pexa-VecThymidine kinase-inactivated vaccinia virus expressing human GM-CSF | Biological | Single Arm |
Primary outcome
Number of Participants With Objective Response in Injected Tumor(s)
Time frame: Initial response assessment after six weeks (Day 43)
Response was evaluated at the participant level based on the sum of the longest diameters of the injected target tumors. Tumor assessments were performed using RECIST criteria. Complete response (CR): all lesions disappear; Partial response (PR): maximum diameter decrease of > 30% of the longest diameter (LD) of target lesions using the baseline LD; Progressive disease (PD): increase of >20% in the sum of LD target lesions using the smallest sum LD recorded since treatment started; Stable disease (SD): unable to categorize as PR or PD using as reference the lobe with the smallest diameter at baseline.
4 secondary outcomes
Incidence of Treatment-related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to Day 64
Best Overall Response for Entire Disease Burden (RECIST Criteria)
Time frame: Initial response assessment after six weeks (Day 43)
Progression-free Survival
Time frame: From first study treatment until objective evidence of disease progression or death, up to 20.5 months
Number of Participants With Objective Response in Non-injected Tumor(s)
Time frame: Initial response assessment after six weeks (Day 43)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10505851Mastrangelo 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. doi: 10.1038/sj.cgt.7700066.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Burke, M.D. principal investigator
Billings Clinic
David H Kirn, M.D. study director
Jennerex Biotherapeutics
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing JX-594 in people with Melanoma, run by Jennerex Biotherapeutics at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Objective Response in Injected Tumor(s) (time frame: Initial response assessment after six weeks (Day 43)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00429312, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2026.