Melanoma
Conditions
Keywords
Melanoma, Oncolytic virus, Pexa-Vec
Brief 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.
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.
Interventions
BIOLOGICALJX-594
Thymidine kinase-inactivated vaccinia virus expressing human GM-CSF
Sponsors
Jennerex Biotherapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Response in Injected Tumor(s) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-related Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Day 64 | 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. |
| Best Overall Response for Entire Disease Burden (RECIST Criteria) | Initial response assessment after six weeks (Day 43) | 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 \[PD\]). |
| Progression-free Survival | From first study treatment until objective evidence of disease progression or death, up to 20.5 months | Progression-free survival was defined as the time from the first study treatment until objective evidence of disease progression or death. |
| Number of Participants With Objective Response in Non-injected Tumor(s) | Initial response assessment after six weeks (Day 43) | 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 \[PD\]). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJames Burke, M.D.
Billings Clinic
STUDY_DIRECTORDavid H Kirn, M.D.
Jennerex Biotherapeutics
Participant flow
Recruitment details
Ten evaluable patients with metastatic or locally invasive, unresectable Stage 3 or Stage 4 malignant melanoma were enrolled. Patients were enrolled and treated at the Billings Clinic, the Cancer Center of the Carolinas, or University of California, Los Angeles (UCLA).
Pre-assignment details
This study was a Phase 1/2, open-label, non-comparative trial, so there are no specific pre-assignment, run-in, or washout periods mentioned.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 65.1 years STANDARD_DEVIATION 11.2 |
| Race/Ethnicity, Customized Hispanic/Latino | 2 participants |
| Race/Ethnicity, Customized White, Not Hispanic/Latino | 8 participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 2 / 10 |
Outcome results
None listed