Safety Study of Recombinant Vaccinia Virus to Treat Refractory Solid Tumors

Lung Cancer Clinical Trial

Official title:

A Phase I Dose Escalation Study of JX-594 (Thymidine Kinase-deleted Vaccinia Virus Plus GM-CSF) Administered by Intravenous Infusion in Patients With Refractory Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00625456
• Other study ID #: JX594-IV-011
• Status: Completed
• Phase: Phase 1
• First received: February 19, 2008
• Last updated: November 30, 2015
• Start date: June 2008
• Est. completion date: June 2014

Study information

• Verified date: March 2012
• Source: SillaJen, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: June 2014
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms
• Lung Cancer
• Melanoma
• Renal Cell Carcinoma
• Squamous Cell Carcinoma of the Head and Neck
• Vaccinia

Intervention

Drug:
• Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)
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

Locations

Country	Name	City	State
Canada	Ottawa Health Research Institute	Ottawa	Ontario
United States	Billings Clinic	Billings	Montana
United States	Cancer Centers of the Carolinas	Greenville	South Carolina
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Jennerex Biotherapeutics

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of JX-594 administered by intravenous (IV) infusion		4 weeks	Yes
Primary	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	Yes
Secondary	Determine the JX-594 pharmacokinetics and pharmacodynamics over time following IV infusion		4 weeks	No
Secondary	Determine the immune response to JX-594 following IV infusion		4 weeks	No
Secondary	Determine the delivery of JX-594 to, and concentration within, solid tumors following IV infusion		4 weeks	No