Phase I Study of the Safety, Tolerability,and Tumor-Specific Replication of the Intravenous Administration of Green Fluorescent Protein Encoded Genetically Engineered Attenuated Vaccinia Virus, GL-ONC1, in Patients With Advanced Solid Organ Cancers.
- Diagnosis of histologically or cytologically documented, advanced stage, primary or
metastatic solid tumors refractory to standard therapy or for which no curative
standard therapy exists.
- Evidence of measurable or evaluable disease.
- Age must be ≥ 18 years.
- All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical
procedures must have resolved to Common Terminology Criteria for Adverse Events
(CTCAE, Version 3.0) Grade ≤ 1. Surgery must have occurred at least 28 days prior to
- Chemotherapy or radiotherapy (other than small-field palliative radiotherapy),
immunotherapy and/or hormonal therapy must have been received > 28 days prior to
receiving study drug. Subjects may continue to receive LHRH analogue therapy for
prostate cancer in face of rising PSA. Bisphosphonates and anticoagulants are
- ECOG Performance Score ≤ 1.
- Life expectancy of at least 3 months.
- Required baseline laboratory data include:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9 [SI units 10^9/L]
- Platelets ≥ 100 x 10^9 [SI units 10^9/L]
- Haemoglobin ≥ 9.0 g/dL [SI units gm/L]
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
- Bilirubin ≤ 1.5 x ULN
- AST/ALT ≤ 2.5 x ULN or ≤ 5 x ULN in the presence of liver metastases
- Ejection fraction of ≥50% by MUGA or ECHO.
- Signed informed consent indicating that the subject is aware of the neoplastic nature
of his or her disease and has been informed of the procedures to be followed, the
experimental nature of the therapy, the alternatives and the potential benefits, side
effects, risks, and discomforts.
- Willing and able to comply with scheduled visits, treatment plan, and laboratory
- Female patients must have a negative pregnancy test within five days prior to
- Female patients of childbearing potential who are not surgically sterile or
postmenopausal and male patients who are not surgically sterile must agree to use
highly effective contraception. Barrier methods for contraception must be applied
during the treatment period and up to day 60 after the last virus application. The
patient must agree to sign his or her consent on this particular inclusion criterion.
Additional Inclusion Criteria Relevant for Cohort 8 and the Phase IB Expansion Cohort:
1. Diagnosis of histologically or cytologically documented, advanced stage solid tumor
(e.g., primary or metastatic breast, prostate or colorectal cancer) refractory to
standard therapy or for which no curative standard therapy exists.
2. Evidence of measurable or evaluable disease.
3. Disease that can be safely serially biopsied.
4. Circulating tumor cell count > 10 for analyses of tumor cell viral delivery.
- Prior therapy with a cytolytic virus of any type.
- Concurrent therapy with any other investigational anticancer agent.
- Concurrent vaccines or immunotherapy during, and for 30 days before or after, study
- Concurrent antiviral agent active against vaccinia virus (e.g. cidofovir, vaccinia
immunoglobulin, imatinib, ST-246) during course of study.
- Patients vaccinated with vaccinia virus within the past 10 years.
- Patients with known brain metastases: due to poor prognosis and risk of developing
progressive neurological dysfunction that would confound the evaluation of
neurological or other adverse events.
- Patients with known allergy to ovalbumin or other egg products.
- Patients with immune system disorders or who are receiving immunosuppressive therapy
or any steroids.
- Patients with clinically significant dermatological disorders, e.g. eczema or
psoriasis, or any unhealed skin wounds or ulcers, as assessed by the principal
investigator during the screening and during the study.
- Patients with fevers, or any systemic infections, including known HIV infection,
hepatitis B or C.
- Prior splenectomy.
- Previous organ transplant.
- Pregnant or breast-feeding women.
- Clinically significant cardiac disease (New York Heart Association, Class III or IV)
including pre-existing arrhythmia, uncontrolled angina pectoris or myocardial
infarction within one year prior to study entry, or grade 2 or higher compromised
left ventricular ejection fraction (as determined by MUGA).
- Dementia or altered mental status that would prohibit informed consent.
- Other severe, acute, or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration or may interfere with the interpretation of study results and, in
the judgment of the principal investigator, would make the subject inappropriate for