Ph 1-2 Study ADI-PEG 20 Plus FOLFOX in Subjects With Advanced GI Malignancies Focusing on Hepatocellular Carcinoma

Phase 2 HCC Subjects:

1. Advanced histologically or cytologically proven HCC (except with prior liver transplantation).

2. Treatment with at least 2 prior systemic therapy regimens.

3. Child-Pugh grade A. Child-Pugh status should be determined based on clinical findings and laboratory data during the screening period (Appendix C).

4. Measurable disease using RECIST 1.1 criteria (Appendix A). At least 1 measurable lesion must be present. Subjects who have received local-regional therapies are eligible, provided that they have either a target lesion which has not been treated with local therapy and/or the target lesion(s) within the field of the local regional therapy has shown an increase of ≥ 20% in size. Local-regional therapy must be completed at least 4 weeks prior to the baseline CT scan.

5. ECOG performance status of 0 - 1.

6. Expected survival of at least 3 months.

7. Age ≥ 18 years.

8. Fully recovered from any prior surgery and no major surgery within 4 weeks of initiating treatment. Surgery or procedure for placement of vascular access devices is exempt from this period.

9. Subjects must agree to use at least one form of highly effective contraception or agree to refrain from intercourse for the duration of the study. Contraceptive use must be continued until at least 30 days after the last administration of ADI-PEG 20 and at least 90 days after the last administration of FOLFOX. For female subjects, a serum human chorionic gonadotropin (HCG) pregnancy test must be negative before entry into the study. If HCG pregnancy test is positive, further evaluation to rule out pregnancy must be performed according to GCP before this patient is claimed eligible.

10. Informed consent must be obtained prior to study initiation.

11. No concurrent investigational studies are allowed.

12. Total bilirubin \< 1.5 x upper limit of normal range.

13. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x upper limit of normal range.

14. Absolute neutrophil count (ANC) \> 1500/μL.

15. Platelets \> 75,000/μL.

16. Serum uric acid ≤ 8 mg/dL (with or without medication control).

17. Serum creatinine ≤ 1.5 x the upper limit of normal range, or, if serum creatinine \>1.5 x the upper limit of normal range, then the creatinine clearance must be ≥ 60 mL/min/1.73 m2 (calculated using the Jelliffe equation: calculated creatinine clearance = 98 - 0.8 \[age (yrs.) - 20\] /serum creatinine (x 0.9 if female).

18. Brain metastases are allowed if well controlled and without seizures.

19. Serum albumin level ≥ 2.8 g/dL.

20. Prothrombin time (PT)-international normalized ratio (INR): PT \<6 seconds above control or INR \<1.7. Subjects on Coumadin anti-coagulants are to receive only 1 point for their INR status.

21. Subjects with active hepatitis B or C on anti-viremic compounds may remain on such treatment, except for interferon.

What this study is about