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

NCT01380600 | Completed Phase 1

• 1 other identifier: JX594-IV-CRC014
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Carcinoma, Colorectal

Keywords

Vaccinia; Vaccinia Virus; JX-594; Jennerex; Colorectal Carcinoma; Colorectal cancer; Colon Cancer; Rectal Cancer; Pexa-Vec

Outcome Measures

Primary Outcomes (2)

• Determine the maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of JX-594 administered by biweekly intravenous (IV) infusion

  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.

  DLT evaluations through 14 days following last JX-594 treatment

• Determine the safety of JX-594 administered by biweekly IV infusion

  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).

  Safety evaluations through 28 days after last dose of JX-594

Secondary Outcomes (2)

• Determine the pharmacokinetics, pharmacodynamics and immune response activity of JX-594

  Blood samples collected at assigned time points from baseline through Week 8

• Determine the anti-tumoral response of JX-594

  Disease control and response assessment at Week 8

Study Arms (1)

single arm; Dose escalation

OTHER

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)

Interventions

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

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.

Also known as: JX-594

single arm; Dose escalation

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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
• Women who are pregnant or nursing an infant

Sponsors & Collaborators

• Jennerex Biotherapeutics: lead
• Samsung Medical Center: collaborator

Study Sites (1)

Samsung Medical Center

Seoul, South Korea

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Vaccinia; Colonic Neoplasms; Rectal 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; Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2011
• First Posted: June 27, 2011
• Study Start: July 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: December 1, 2015
• Last Updated: January 8, 2016

Record last verified: 2012-03

Locations

KR (1)