Clinical trial NCT01380600: Safety Study of Recombinant Vaccinia Virus Administered Intravenously in Patients With Metastatic, Refractory Colorectal Carcinoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Colorectal
Keywords: Vaccinia
Vaccinia Virus
JX-594
Jennerex
Colorectal Carcinoma
Colorectal cancer
Colon Cancer
Rectal Cancer
Pexa-Vec
Lead sponsor: SillaJen, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Samsung Medical Center
First posted: 2011-06-27
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Determine the maximally-tolerated dose (MTD) and/or maximum-feasible dose (MFD) of JX-594 administered by biweekly intravenous (IV) infusion
timeFrame: DLT evaluations through 14 days following last JX-594 treatment
measure: Determine the safety of JX-594 administered by biweekly IV infusion
timeFrame: Safety evaluations through 28 days after last dose of JX-594
Secondary outcomes:
measure: Determine the pharmacokinetics, pharmacodynamics and immune response activity of JX-594
timeFrame: Blood samples collected at assigned time points from baseline through Week 8
measure: Determine the anti-tumoral response of JX-594
timeFrame: Disease control and response assessment at Week 8
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
References: