Neoadjuvant Study of Recombinant Vaccinia Virus to Treat Metastatic Colorectal Carcinoma in Patients Undergoing Complete Resection of Liver Tumors

NCT01329809 | Terminated Phase 2 DMC

• 1 other identifier: JX594-HEP012
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is a neoadjuvant Phase 2a, open-label trial in patients with metastatic colorectal carcinoma who are undergoing a complete resection of the metastatic colorectal tumors in their liver.

Conditions

Colorectal Carcinoma

Keywords

metastatic colorectal cancer; colon cancer; liver metastasis; Pexa-vec; JX-594

Outcome Measures

Primary Outcomes (1)

• Delivery to and replication within tumors

  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

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

Secondary Outcomes (3)

• JX-594 spread to, and replication within, non-injected tumors after IT JX-594 injection

  Day 1

• Modified Choi response assessment

  Day 8-14

• Toxicity: Grade I-IV Adverse Events (according to CTCAE)

  Day 1- Day 43

Study Arms (2)

JX-594 Intravenous infusion

EXPERIMENTAL

JX-594 will be administered intravenously to patients with measurable intra-hepatic disease who are not eligible for intratumoral injection of JX-594.

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

JX-594 Intratumoral Injection

EXPERIMENTAL

JX-594 will be injected directly into the liver tumor of patients who have at least two measurable intra-hepatic tumors, one of which must be at least 1.5cm in diameter and safety injectable.

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

Interventions

Recombinant Vaccinia GM-CSF; RAC VAC GM-CSF (JX-594) DRUG

intratumoral or intravenous dosage: 10e9 pfu Intravenous: administered over 60 minutes Intratumoral: direct injection into a single liver lesion

Also known as: JX-594

JX-594 Intratumoral Injection; JX-594 Intravenous infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 eligible)
• 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

You may not qualify if:

• 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 treatment).
• Absolute contraindication to undergoing MRI scanning (e.g. pacemaker, paramagnetic intracranial aneurysm clip, inner ear implants, fragments of metal within the body, etc.).
• Pulse oximetry O2 saturation \< 90% at rest
• Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination

Sponsors & Collaborators

• Jennerex Biotherapeutics: lead

Study Sites (1)

Ottawa Hospital and Research Institute (OHRI)

Ottawa, Ontario, K1H 8L6, Canada

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Rebecca C Auer, MD

  OHRI

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2011
• First Posted: April 6, 2011
• Study Start: October 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: March 1, 2013
• Last Updated: April 10, 2013

Record last verified: 2011-07

Locations

CA (1)