GOAT; Phase I Open Label Study of CGTG-102, a GM-CSF Encoding Oncolytic Adenovirus, for Advanced Cancers

INCLUSION CRITERIA:

1. Age 18 - 70 years
2. Histologically-confirmed, advanced/metastatic solid tumor that is relapsed and/or refractory to standard therapy (progressive disease despite therapy).
3. Cancer is not surgically resectable for cure.
4. At least one measurable tumor mass by PETCT (i.e. PET-positive lesion that can reliable be assessed for SUV (standard update value) peak/SUV max, typically featuring longest diameter greater than or equal to 1 cm) and that can be injected by direct visualization/palpitation or by imaging-guidance (ultrasound)
5. Tumor suitable for biopsy. Biopsy is to be performed twice during the study (day 1 and day 15). The aim is to biopsy the same tumor at these visits.
6. Expected survival for approximately 12 weeks or longer
7. Performance Status WHO (World Health Organization) 0-2
8. Total bilirubin less than or equal to ULN (Upper Limit of Normal)
9. AST (Aspartate transaminase), ALT (Alanine aminotransferase) less than or equal to 3.0 × ULN
10. Serum creatinine less than or equal to 1.5 x ULN
11. INR (International Normalized Ratio) less than or equal to 1.5 x ULN
12. Hematologic parameters: Patients can be transfused to meet these entry criteria:

    1. Hemoglobin greater than or equal to 10 g/dL
    2. Leucocytes greater than or equal to 2300/mL
    3. platelet count greater than or equal to 75,000 plts/mm
13. Willing to participate as demonstrated by signed informed consent form.

EXCLUSION CRITERIA:

1. Known brain metastases or glioma. Central Nervous System malignancy, including carcinomatosis meningitis.
2. Tumor in the immediate pericardial vicinity
3. Use of high dose systemic corticosteroids or other immune suppressive medication within 3 weeks of first treatment.

   Note: patients taking low-dose corticosteroids for the treatment of nausea and/or taking maintenance corticosteroids for adrenal insufficiency are permitted to enroll.
4. Known infection with HIV (Human immunodeficiency virus) as this would affect the immune response of treatment or known underlying genetic immunodeficiency disease
5. Treatment of the injected tumor(s) with radiotherapy, chemotherapy, surgery, or an investigational drug within 4 weeks prior to first treatment.
6. Use of anti-viral medication. \[Patients who discontinue such medications within 7 days prior to first treatment may be eligible for this study.\]
7. Recent thromboembolic event
8. Clinically significant active infection or uncontrolled medical condition considered high risk for investigational new drug treatment (e.g. pulmonary, neurological, cardiovascular, metabolic such as type 2 diabetes, clinically significant and/or rapidly accumulating ascites, peri-cardial and/or pleural effusions)
9. Severe or unstable cardiac disease.
10. Current, active, progressing CNS (Central nervous system) malignancy, including carcinomatosis meningitis (definitively surgically resected or irradiated metastases allowed)
11. Pulse oximetry O2 (oxygen) criterion \<90% at rest on room air
12. Vaccination with a live virus (i.e. measles, mumps, rubella, etc) \< 30 days prior to first treatment
13. History of hepatic dysfunction, cirrhosis, hepatitis or malaria
14. Evidence of coagulation disorder
15. Women who are pregnant or nursing an infant
16. Previous organ transplant