Safety and Efficacy of Intra-Arterial and Intra-Tumoral Ad-p53 With Capecitabine (Xeloda) or Anti-PD-1 in Liver Metastases of Solid Tumors and Recurrent Head and Neck Squamous Cell Cancer

1. Signed informed consent

2. Male or female, age 18 or above, who agree to use barrier contraception throughout the study. Females of child-bearing potential must be non-pregnant and non-lactating throughout the study.

3. Histologically or cytologically confirmed solid tumors or hepatocellular carcinoma with known disease progression.

4. Each patient entered on the study must have disease that is evaluable for response using RECIST 1.1 criteria with a minimum size of 1 cm by CT/MRI or physical examination

5. Carcinoma patients in Arm A or Arm B must have received at least 1 prior regimen of standard of care systemic antitumor therapy for their metastatic disease and experienced tumor progression within 3 months after the last prior administration of the therapy or experienced unacceptable toxicity to these treatments.

6. Subjects in Arm A and Arm B should have measurable CT evidence of liver metastases or liver lesions that are not treatable by surgical resection or local ablation in consultation with hepatobiliary specialist.

7. The maximum tumor diameters for each Cohort for both Arm A and Arm B should achieve a dose of approximately 1x1011 viral particles (vp)/cm3 of tumor volume. (see Table 1). Please refer to Table for calculating tumor volume.

8. ECOG Performance Status 0 - 1

9. Either no brain metastases or irradiated stable brain metastases

10. Life expectancy at least 3 months

11. No prior autologous or allogeneic organ or tissue transplantation

12. PT/international normalized ratio (INR) ≤ULN; aPTT ≤ULN.

13. ANC ≥1500 cells/mm3

14. Platelet count ≥100,000 cells/mm3

15. Hemoglobin ≥9.0 g/dL

16. Creatinine \<2.0 mg/dL or creatinine clearance ≥50 mL/min

17. Total bilirubin \<1.5 x ULN

18. AST and ALT \<3.0 x ULN

19. Alkaline phosphatase ≤5 x ULN

20. Negative pregnancy test in women of childbearing potential

21. Fertile patients must use effective contraception

22. No non-approved investigational agents or procedures ≤4 weeks of study entry

23. Patients with PRIMARY HEPATIC CANCER must have an undetectable viral load for Hepatitis B and C.

24. Patients with Primary Hepatic Cancer have not recently been treated with antivirals.

25. Troponin blood level within normal limits.

26. Favorable biomarker profile defined by either wild type p53 gene sequence or less than 20% p53 positive tumor cells by immunohistochemistry

27. Echocardiogram with normal ejection fractions

28. Normal lung oxygen saturation by pulse oximeter, as determined by the Principal Investigator based on patient history and status.

29. Arm C patients must have loco-regional recurrent head and neck squamous cell carcinoma (HNSCC), excluding endolaryngeal recurrence, meeting the following criteria:

* Tumor progression within 6 months of platinum-based chemotherapy

* All HNSCC lesions should be in the head and neck region and suitable for intra-tumoral injection

* The total sum of Ad-p53 Injection Doses (mL) based upon the tumor volumes shown in Table 2 should be less than or equal to 25 mL as the MTD of Ad-p53 is 2.5 x1013 vp/treatment day.

What this study is about