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
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)