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A Phase IIa Study of Neoadjuvant JX-594 (Thymidine Kinase-Deactivated Vaccinia Virus Plus GM-CSF) Administered by Intravenous Infusion or Intratumoral Injection Followed by Surgical Resection in Patients With Metastatic Colorectal Tumors Within the Liver

Phase 2
18 Years
Not Enrolling
Colorectal Carcinoma

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Trial Information

A Phase IIa Study of Neoadjuvant JX-594 (Thymidine Kinase-Deactivated Vaccinia Virus Plus GM-CSF) Administered by Intravenous Infusion or Intratumoral Injection Followed by Surgical Resection in Patients With Metastatic Colorectal Tumors Within the Liver

Patients will receive either an intravenous infusion or an intratumoral injection of JX-594
(Pexa-Vec) directly into one liver lesions at Day 1. Patients will undergo a complete
resection of all liver tumors at Day 15. Patients will then be monitored throughout their
life for disease recurrence and/or general overall survival.

Inclusion Criteria:

- The planned surgical resection must be margin negative with complete resection or
resection plus radiofrequency ablation (RFA) of metastatic CRC as determined by
principal investigator or surgeon

- Diagnosis of histologically-confirmed metastatic colorectal tumor(s) within the liver
eligible for surgical resection. Eligible patients must have: preoperative work-up
that reveals potential resectability (CT scan or MRI of the abdomen and pelvis and CT
scan of the chest within 6 weeks of enrollment) preoperative work-up to ensure
operability with general medical clearance as indicated

- At least one measurable tumor mass by MRI (i.e. lesion that can accurately be
measured in at least one dimension with longest diameter ≥ 1 cm)

- Plan for a maximum resection of six (6) liver segments

- Child Pugh A (Refer to APPENDIX C: Child-Pugh Classification

- Performance Score: KPS score of ≥ 70

- Age ≥18 years

- For patients treated with IT injection only: at least 1 intra-hepatic tumor with
longest diameter (LD) ≥ 1.5 cm and ≤ 12 cm and which is technically amenable to
injection under radiographic guidance targeted for surgical resection.

- In patients treated with IT injection, the injected tumor must be included in the
surgical resection specimen (a planned RFA of the injected tumor would not be

- Total bilirubin ≤ 3 x ULN

- AST, ALT < 5.0 x ULN

- WBC ≥ 3.5x 109/L and ≤ 50 x 109/L

- ANC ≥1.5 x 109/L

- CD4 ≥ 200 total cells/mm3

- Hemoglobin ≥ 80g/L

- Platelet count ≥ 100 x 109/L

- Acceptable coagulation status: INR ≤ 1.4

- Creatinine ≤ 2 x ULN

- Serum Sodium, Potassium and Calcium levels ≤ Grade 1

- If patients are diabetic or have a screening random glucose > 8.9mmol/L, a fasting
glucose must be done and results must be WNL or Grade 1 in order to be eligible for
the study.

- For patients who are sexually active: patient must be able and willing to abstain
from sex during JX-594 treatment period (to prevent pregnancy) and willing to use
barrier method for at least 6 weeks after the last JX-594 treatment (to protect
partner against infection).

- Able and willing to sign an Institutional Review Board (IRB)/Independent Ethics
Committee (IEC)/Research Ethics Board (REB)-approved written consent form Able and
willing to comply with study procedures and follow-up examinations, including
compliance with the "Infection Control Guidelines for Patients" contained within the
written consent form.

Exclusion Criteria:

- Prior local-regional treatment (including hepatic arterial infusion, hepatic
embolization, radiofrequency ablation) for tumor downstaging. Prior adjuvant
chemotherapy will be accepted as long as the duration between chemotherapy and the
development of metastases has been >8 weeks.

- Pregnant or nursing an infant

- Known myeloproliferative disorders requiring systemic therapy

- Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or
medication (e.g. high dose systemic corticosteroids taken for more than 4 weeks
within the preceding 3 months)

- History of severe exfoliative skin condition (e.g. eczema or atopic dermatitis
requiring systemic therapy for more than 4 weeks)

- Tumor(s) invading a major vascular structure (e.g. carotid artery)

- Clinically significant and/or rapidly accumulating ascites, pericardial and/or
pleural effusions

- Clinically significant active infection, requiring systemic antibiotic therapy, or
uncontrolled medical condition which would, in the opinion of the principle
investigator, impair the ability of the subject to receive protocol therapy

- Severe or unstable cardiac disease, including significant coronary artery disease
requiring angioplasty or stenting within the preceding 12 months, unless
well-controlled and on stable medical therapy for at least 3 months

- Known viable CNS malignancy (history of completely resected or irradiated brain
metastases allowed)

- Chronic use of anti-platelet or anti-coagulation medication that cannot be
temporarily discontinued for at least seven days prior to treatment with JX-594.
(Note: the following are allowed: low dose aspirin ≤ 100 mg, low dose coumadin as
long as INR ≤ 1.4 and low-dose heparin to maintain port access)

- Use of the following anti-viral agents: ribavirin, adefovir, cidofovir (at least 7
days prior to the first treatment), and PEG-IFN (at least 14 days prior to the first

- Absolute contraindication to undergoing MRI scanning (e.g. pacemaker, paramagnetic
intracranial aneurysm clip, inner ear implants, fragments of metal within the body,

- Pulse oximetry O2 saturation < 90% at rest

- Experienced a severe systemic 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 meet any of these criteria will be excluded
unless alternate living arrangements can be made during the patient's dosing period
and for at least 7 days following the last dose of study medication

- Pregnant or nursing an infant

- Children < 1 year old

- People with skin disease (eczema, atopic dermatitis and related diseases

- Immunocompromised hosts (severe deficiencies in cell-mediated immunity, including
AIDS, organ transplant recipients, hematologist malignancies)

Type of Study:


Study Design:

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

Outcome Measure:

Delivery to and replication within tumors

Outcome Description:

IT injection: replication and dissemination of JX-594 following injection of a single colorectal metastasis within the liver. A positive replication response is defined as a > 2-fold increase in viral genome concentration in the blood(as measured in the first 12 hours following injection) within the first 14 days following treatment. Note: Viral genomes will be measured in the blood by Q-PCR at baseline, on Day 1 (15 minutes, 3 hours & 8 hours) post-treatment and on Days 3, 5, 8, 11 and 15. IV infusion: assessment of viral gene & protein expression in histologic samples of tumor tissue

Outcome Time Frame:

Day 1, 3, 5, 8, 11, and 15

Safety Issue:


Principal Investigator

Rebecca C Auer, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

October 2011

Completion Date:

March 2013

Related Keywords:

  • Colorectal Carcinoma
  • metastatic colorectal cancer
  • colon cancer
  • liver metastasis
  • Pexa-vec
  • JX-594
  • Carcinoma
  • Colorectal Neoplasms
  • Vaccinia