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Safety Study of Recombinant Vaccinia Virus Administered Intravenously in Patients With Metastatic, Refractory Colorectal Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01380600
Recruitment Status : Completed
First Posted : June 27, 2011
Last Update Posted : January 8, 2016
Samsung Medical Center
Information provided by (Responsible Party):
SillaJen, Inc. ( Jennerex Biotherapeutics )

Brief Summary:
The purpose of this pilot safety study is to evaluate the safety and tolerability of JX-594 (Pexa-Vec) administered intravenously every 2 weeks in colorectal carcinoma patients who are refractory to or intolerant of oxaliplatin, irinotecan, and Erbitux treatments.

Condition or disease Intervention/treatment Phase
Carcinoma, Colorectal Drug: Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594) Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Dose Escalation Study of JX-594 (Thymidine Kinase-Inactivated Vaccinia Virus Plus GM-CSF) Administered by Biweekly (Every Two Weeks) Intravenous Infusion in Patients With Metastatic, Refractory Colorectal Carcinoma
Study Start Date : July 2010
Actual Primary Completion Date : November 2012
Actual Study Completion Date : December 2015

Arm Intervention/treatment
single arm; Dose escalation
Dose escalation 1e6 pfu/kg bw, 1e7 pfu/kg bw, 3e7 pfu/kg bw of Recombinant Vaccinia GM-CSF JX-594
Drug: Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594)
Intravenous Dose Range: 1x10^6 pfu/kg, 1x10^7 pfu/kg, 3x10^7 pfu/kg Up to 4 intravenous infusions administered over 60 minutes every 2 weeks.
Other Name: JX-594

Primary Outcome Measures :
  1. Determine the maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of JX-594 administered by biweekly intravenous (IV) infusion [ Time Frame: DLT evaluations through 14 days following last JX-594 treatment ]
    Any of the following treatment related adverse events: Grade 4 toxicity, Grade 3 hematologic toxicity for > 5 days, Grade 3 non-hematologic toxicities persisting for > 7 days except for flu-like symptoms that respond to standard therapies.

  2. Determine the safety of JX-594 administered by biweekly IV infusion [ Time Frame: Safety evaluations through 28 days after last dose of JX-594 ]
    Adverse events will be collected and assessed to assess safety and tolerability through 28 days after last dose of JX-594 (or until all events considered probably or possibly related to JX-594 have resolved, stabilized, or returned to baseline status).

Secondary Outcome Measures :
  1. Determine the pharmacokinetics, pharmacodynamics and immune response activity of JX-594 [ Time Frame: Blood samples collected at assigned time points from baseline through Week 8 ]
    Change over time in viral genomes, infectious units, GM-CSF concentration, peripheral white blood cell counts, plasma cytokine measurements, and neutralizing antibodies to JX-594 in blood and/or serum.

  2. Determine the anti-tumoral response of JX-594 [ Time Frame: Disease control and response assessment at Week 8 ]
    Tumor response (Stable, partial, complete, progression) by standard RECIST on CT/MRI. Decrease in tumor blood marker.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically-confirmed, advanced/metastatic colorectal carcinoma
  • Failed both oxaliplatin and irinotecan based regimens for advanced/metastatic disease (if tumor advanced either immediately or within 3 months of the end of treatment)
  • Resistance to Erbitux: patients with Ras mutations, or for whom Erbitux has failed (if tumor advanced either immediately or within 3 months of the end of treatment, or there is no response to Erbitux therapy due to a lack of expression of EGFR (epidermal growth factor))
  • Karnofsky Performance Score (KPS) ≥ 70
  • Age ≥18 years
  • Laboratory Safety: WBC ≥ 3,500 cells/mm3 and ≤ 50,000 cells/mm3, ANC ≥ 1,500 cells/mm3, Hemoglobin ≥ 10 g/dL (transfusion allowed), Platelet count ≥ 100,000 plts/mm3,Total bilirubin ≤ 1.5 X ULN, INR ≤ 1.5, AST, ALT ≤ 2.5x ULN (in case of liver metastasis: AST,ALT ≤5.0 x ULN)
  • Serum chemistries within normal limits (WNL) or Grade 1 (excluding alkaline phosphatase) - If patients are diabetic, a fasting glucose must be done and patients must be > 160 mg/dL.
  • Patients who, if they are sexually active, are willing and able to refrain from sexual activity for 3 weeks following JX-594 administration. Patients who are willing and able to use a permitted contraceptive for 3 months after the final administration of JX-594.

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
  • History of acquiring opportunistic infections.
  • 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
  • Clinically uncontrolled and/or rapidly accumulating ascites, pericardial and/or pleural effusions
  • History of severe or unstable cardiac disease
  • Current, known CNS malignancy (history of completely resected or irradiated brain metastases by WBRT or stereotactic radiosurgery allowed)
  • Administered 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.] Low dose aspirin (approximately 81 mg) allowed.
  • Pulse oximetry O2 saturation <90% Pulse oximetry O2 saturation <90% at rest
  • Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination
  • Pregnant or nursing
  • Household contact exclusions:
  • Women who are pregnant or nursing an infant
  • Children < 5 years old
  • People with skin disease (e.g. eczema, atopic dermatitis, and related diseases
  • Immunocompromised hosts (severe deficiencies in cell-mediated immunity, including AIDS, organ transplant recipients, hematologic malignancies)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01380600

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Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Sponsors and Collaborators
Jennerex Biotherapeutics
Samsung Medical Center

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Responsible Party: Jennerex Biotherapeutics Identifier: NCT01380600     History of Changes
Other Study ID Numbers: JX594-IV-CRC014
First Posted: June 27, 2011    Key Record Dates
Last Update Posted: January 8, 2016
Last Verified: March 2012
Keywords provided by SillaJen, Inc. ( Jennerex Biotherapeutics ):
Vaccinia Virus
Colorectal Carcinoma
Colorectal cancer
Colon Cancer
Rectal Cancer
Additional relevant MeSH terms:
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Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Poxviridae Infections
DNA Virus Infections
Virus Diseases
Immunologic Factors
Physiological Effects of Drugs