Lung Cancer, Melanoma, Renal Cell Carcinoma, Squamous Cell Carcinoma of the Head and Neck
Conditions
Keywords
phase I, advanced metastatic solid tumors, oncolytic virus, vaccinia virus, melanoma, lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck, Pexa-Vec
Brief summary
This is a Phase I, open-label, dose-escalation trial in patients with advanced/metastatic solid tumors refractory to standard therapy; tumors may include malignant melanoma, non-small cell lung cancer, renal cell carcinoma, and squamous cell carcinoma of the head and neck. These tumor types were selected because evidence of biological activity was observed in these tumor types in a Phase I study of JX-594 (Pexa-Vec) administered by intratumoral injection in patients with metastatic disease to the liver. Patients will receive treatment at one of five dose levels in a sequential dose-escalating design.
Interventions
Intravenous Dosage from 1 x 10\^5 pfu/kg to 3 x 10\^7 pfu/kg Intravenous infusion is administered once over a 60 minute period
Sponsors
Jennerex Biotherapeutics
Study design
Allocation
NON_RANDOMIZED
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, advanced/metastatic solid tumor refractory to standard therapy or the patient has refused or does not tolerate the standard therapy; tumors may include malignant melanoma, non-small cell lung cancer, renal cell carcinoma, and squamous cell carcinoma of the head and neck * At least one measurable tumor mass by CT/MRI (i.e. lesion that can accurately be measured in at least one dimension with longest diameter \> 1 cm) * At least one tumor mass amenable to biopsy and/or FNA * Expected survival for approximately 16 weeks or longer * Karnofsky Performance Score (KPS) ≥ 70 * Age ≥18 years * WBC ≥ 3,500 cells/mm3 and ≤ 50,000 cells/mm3 * ANC ≥ 1,500 cells/mm3 * Hemoglobin ≥ 10 g/dL * Platelet count ≥ 100,000 plts/mm3 * Total bilirubin ≤ 1.5 x ULN * AST, ALT ≤ 2.5 x ULN * Serum chemistries within normal limits (WNL) or Grade 1 - If patients are diabetic or have a screening random glucose \> 160 mg/dL, a fasting glucose must be done and patients must be WNL or Grade 1 in order to be eligible for the study. * Acceptable coagulation status: INR ≤ (ULN + 10%) * CD4 count ≥ 500/mm3
Exclusion criteria
* Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids) * Known myeloproliferative disorders requiring systemic therapy * History of exfoliative skin condition (e.g. eczema or ectopic dermatitis) requiring systemic therapy * Tumor(s) invading a major vascular structure (e.g. carotid artery) * Tumor(s) in location that would potentially result in significant clinical adverse effects if post-treatment tumor swelling were to occur (e.g. tumors impinging on the upper airway or affecting biliary tract drainage, etc.) * Clinically significant and/or rapidly accumulating ascites, peri-cardial and/or pleural effusions * Severe or unstable cardiac disease * Current, known CNS malignancy (history of completely resected or irradiated brain metastases allowed) * Received anti-cancer therapy within 4 weeks prior to first treatment (6 weeks in case of mitomycin C or nitrosoureas) * Use of anti-viral, anti-platelet, or anti-coagulation medication \[Patients who discontinue such medications within 7 days prior to first treatment may be eligible for this study.\] * Pulse oximetry O2 saturation \<90% at rest * Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination Household contact exclusions: * Women who are pregnant or nursing an infant * Children \< 5 years old * History of exfoliative skin condition (e.g. eczema) that at some stage has required systemic therapy * Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of JX-594 administered by intravenous (IV) infusion | 4 weeks |
| Safety/Toxicity: Incidence of treatment-related adverse events; treatment-related serious adverse events; treatment-related Grade 3/4 toxicities; and clinically-significant, treatment-related changes from baseline in routine laboratory parameters | 4 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Determine the immune response to JX-594 following IV infusion | 4 weeks |
| Determine the delivery of JX-594 to, and concentration within, solid tumors following IV infusion | 4 weeks |
| Determine the JX-594 pharmacokinetics and pharmacodynamics over time following IV infusion | 4 weeks |
Countries
Canada, United States
Outcome results
None listed