ACRIN 6673

1. ACRIN 6673 Percutaneous Radiofrequency Ablation of Hepatocellular Carcinoma in Cirrhotic Patients: A Multi-Center Study

2. Protocol Team • Gerald D. Dodd, M.D. – P.I. • Jeffrey Blume, Ph.D. – Statistician • Damian Dupuy, M.D. – Radiologist • David Lu, M.D. – Radiologist • Glenn Halff, M.D. – Surg. Oncologist • Shahla Masood, M.D. – Pathologist • Anthony Shields, M.D. – Med. Oncologist

3. Abstract • Primary Objective: To estimate proportion of patients undergoing solitary or repetitive RFA treatment sessions in whom all hepatic tumors can be controlled with no identifiable intrahepatic tumor present by CT scan at 18 months following initiation of therapy

4. Abstract • Important Aspect: Repeat RFA will be allowed throughout the study (for 15 months after initial treatment) in an attempt to control all hepatic tumors.

5. Abstract • Potential Candidates: Adult patients with cirrhosis and HCC in whom surgical resection is contraindicated

6. Abstract • Procedure: All participants will undergo baseline chest and abdomen CT scans.

7. Abstract • Patient Population Heterogeneity Controlled by: • limiting enrollment to participants with minimal intrahepatic hepatic tumor burden and no evidence of extra-hepatic tumor • categorizing participants based on severity of hepatic dysfunction

8. Abstract • Tumor Burden Must Comply With Milan Criteria: • 3 or fewer tumors ≤ 3.0 cm, or • a single tumor > 3.0 cm but ≤ 5 cm in diameter

9. Abstract • Hepatic Dysfunction Defined Using MELD Score • Participants Enrolled Into One of Three Groups: • MELD Score >25 • MELD Score 15-25 • MELD Score <15

10. Abstract • Study Type: Feasibility • Enrollment in Each Cohort: 40 • Each cohort will be closed as target enrollment is achieved. • Total Study Enrollment: 120

11. Abstract • Participants Follow up: • Participants followed for 18 months by serial CT scan after the initial ablation session. • Evidence of residual or recurrent tumor at treated site on or after first 3-month follow-up CT scan classified as a primary failure

12. Abstract • Continued control of all hepatic tumors (baseline, recurrent, and new) may impact survival. • All intrahepatic tumor discovered throughout the study will be ablated as feasible and clinically indicated for 15 months after initiation of ablation therapy.

13. Objectives • Primary Objective: To estimate the proportion of participants undergoing solitary or repetitive RFA treatment sessions whose livers have no identifiable tumor by CT scan at 18 months following initiation of ablative therapy.

14. Objectives • Secondary Objectives: • Explore impact of solitary versus repetitive RFA on the main objective. • Evaluate possible correlation between MELD Score and the main objective. • Estimate local and remote intrahepatic, as well as the extra-hepatic, tumor recurrence rates and their impact on the main objective.

15. Objectives • Explore impact of tumor size on local tumor control rates. • Explore impact of solitary or repetitive RFA with or without local/regional control on the development of extra-hepatic tumor.

16. Eligibility • 18 years and older • Biopsy proven cirrhosis, or typical findings of cirrhosis by CT scan • One of the following: • Biopsy-proven hepatocellular carcinoma (HCC) • Discrete hepatic tumor(s) as defined by Barcelona criteria: 2 imaging studies showing hypervascular tumor > 2cm or single imaging study showing hypervascular tumor > 2cm with AFP ≥ 400 ng/mL • Discrete hypervascular tumor present on two consecutive imaging studies (CT or MRI) with documented growth of > 1cm in diameter

17. Eligibility • Hepatic tumor burden meeting Milan Criteria: 3 or fewer tumors ≤ 3.0 cm, or a single tumor > 3.0 cm but ≤ 5 cm in diameter • All identified tumors deemed treatable by percutaneous RFA by site PI • All tumors ≥ 1 cm from main, right, and left portal veins • All tumors ≥ 1 cm from hollow viscera • Performance status 0-2 on Zubrod Performance Scale

18. Eligibility • Serum creatinine < 2.0 mg/dl • Study-specific signed informed consent • Not a candidate for surgical resection • No previous or current treatment for HCC by any method (radiation therapy, chemotherapy, chemoembolization, cryo-ablation); agrees not to be treated by these therapies while on study.

19. Ablation Equipment • Requirements: • Valley Lab ablation equipment chosen because it is most commonly used by radiologists • Limited to one manufacturer’s device to minimize potential impact of different devices.

20. Ablation Experience • Participating Physician: • must have treated at least 5 of those patients using Valley Lab equipment • must have ablated hepatic tumors in at least 15 patients

21. Procedures: 3-phase CT scans of the abdomen are the only imaging technique for assessing eligibility and for follow-up. Pre-enrollment CT scans of chest and abdomen must be performed within 60 days prior to initial RFA. Imaging

22. Imaging • Follow-up 3-phase CT scans of abdomen must be performed within one week following ablation and every 3 months for 18 months. • If repeat ablation is performed for recurrent tumor, new baseline CT scan must be performed within one week.

23. Pathology • Requirements: • If patient undergoes resection, transplantation, or autopsy, pathological results of the status of tumor in the liver will be recorded. • Those results will not be included in assessment of primary objective.

24. Enrollment • Goals: • Participant accrual will be completed within 1.5 years of activation. • Protocol team hopes enrollment can be completed in 1 year.

25. Thanks The protocol team appreciates the efforts of the individuals and sites working on this protocol.