Safety Study of Recombinant Vaccinia Virus to Treat Refractory Solid Tumors

November 30, 2015 updated by: Jennerex Biotherapeutics

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Health Research Institute
  • United States
    • Montana
      • Billings, Montana, United States, 59101
        • Billings Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • University of Pennsylvania
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Cancer Centers of the Carolinas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single Arm, dose escalation
dose escalation starting dose 1e5 pfu/kg bw to 3e7 pfu/kg bw; Recombinant Vaccinia GM-CSF (JX-594)
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
Other Names:
  • JX-594

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of JX-594 administered by intravenous (IV) infusion
Time Frame: 4 weeks
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
Time Frame: 4 weeks
4 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Determine the JX-594 pharmacokinetics and pharmacodynamics over time following IV infusion
Time Frame: 4 weeks
4 weeks
Determine the immune response to JX-594 following IV infusion
Time Frame: 4 weeks
4 weeks
Determine the delivery of JX-594 to, and concentration within, solid tumors following IV infusion
Time Frame: 4 weeks
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jennerex Biotherapeutics

Investigators

  • Study Director: David Kirn, MD, Jennerex Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2008

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

June 1, 2014

Study Registration Dates

First Submitted

February 19, 2008

First Submitted That Met QC Criteria

February 27, 2008

First Posted (Estimate)

February 28, 2008

Study Record Updates

Last Update Posted (Estimate)

December 3, 2015

Last Update Submitted That Met QC Criteria

November 30, 2015

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JX594-IV-011

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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