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

Carcinoma, Colorectal Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01380600
• Other study ID #: JX594-IV-CRC014
• Status: Completed
• Phase: Phase 1
• First received: June 22, 2011
• Last updated: January 6, 2016
• Start date: July 2010
• Est. completion date: December 2015

Study information

• Verified date: March 2012
• Source: SillaJen, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Korea Food and Drug Administration (KFDA)United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 2015
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Colorectal
• Colorectal Neoplasms
• Vaccinia

Intervention

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.

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Jennerex Biotherapeutics	Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Secondary	Determine the pharmacokinetics, pharmacodynamics and immune response activity of JX-594	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.	Blood samples collected at assigned time points from baseline through Week 8	No
Secondary	Determine the anti-tumoral response of JX-594	Tumor response (Stable, partial, complete, progression) by standard RECIST on CT/MRI. Decrease in tumor blood marker.	Disease control and response assessment at Week 8	No