A Randomized Phase II Trial of Surgery Plus Sorafenib vs. Sorafenib Alone for Hepatocellular Cancer (HCC) With Portal Vein Invasion

Study Overview
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Brief Summary
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Patients with HCC with portal vein involvement not involving the bifurcation (vP1-vP3) and no evidence of extra-hepatic spread will be enrolled. Patients will be required to have Child's A liver function and no significant portal hypertension. Patients will be randomly assigned with a 1:1 ratio to either surgery followed by adjuvant sorafenib or sorafenib alone. Patients will be followed by serial imaging. The primary end-point is overall survival.

Detailed Description
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Trial design Surgery + sorafenib vs. sorafenib 100 patients per arm Centralized randomization by CRO Need to call CRO for treatment allocation Primary end-point - OS Secondary end-point Progression free survival (PFS) Randomized 1:1 Stratification Vp1-2 vs. Vp3 AFP ≤400 vs AFP >400 Intention to treat Surgery aborted or R1-2 resection will remain in surgical arm No cross over CT scan chest/abdomen 4 weeks after surgery as post-operative baseline Will not alter treatment allocation Will allow for PFS measurement in surgical arm CT scan chest/abdomen pelvis Q 12 weeks after initiation sorafenib Patients progressing on sorafenib allowed 2nd line treatment Regorafenib or lenvatinib - if approved in China Dose reduction sorafenib as per protocol

Official Title
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A Randomized Phase II Trial of Surgery Plus Sorafenib vs. Sorafenib Alone for Hepatocellular Cancer (HCC) With Portal Vein Invasion

Conditions
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Hepatocellular Cancer

Intervention / Treatment
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* Procedure: hepatic resection
* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of HCC A) 1st diagnosis of HCC - no prior treatments of HCC B) Diagnosis made by contrast enhanced CT or MRI with arterial and portal phases Arterial enhancement Venous washout Expanding/enhancing tumor thrombus seen in portal vein Extent of HCC spread A) Vp1-3 (Japanese system) - VP1-2 (Cheng criteria - Shanghai) B) No involvement of main portal vein Vp4 (Japanese system) - Vp3 Shanghai C) No evidence of extra-hepatic spread in abdomen D) No evidence of hepatic vein or vena cava invasion Need for Biopsy A) Patients not meeting above criteria B) Absence of underlying liver disease Demographics A) Age ≥ 18 Women of reproductive age A) Negative pregnancy test B) Must be on birth control for duration of study Able to provide informed consent No prior malignancy A) Excluding basal/squamous cell skin cancers B) Excluding superficial bladder cancer C) Excluding cervical cancer Underlying liver disease A) HBV, HCV, alcohol, or none B) All HBV patients must be placed on anti-viral therapy prior to any treatment and continue through entire study C) Co-infection HBV with HCV excluded D) HIV infection excluded Liver function/Performance status A) Child's A or B7 liver function B) Absence of clinical portal hypertension a. Platelet count ≥ 100,000 b. No evidence of varices or splenomegaly on imaging c. No ascites ECOG performance status 0-1 Tumor characteristics A) Size of largest tumor ≤ 10cm B) <50% of liver volume involved by tumor C) Multiple tumors allowed D) All tumors all confined to same lobe as PV involvement E) Hepatic Vein or Inferior Vena Cava involvement excluded Non-contrast CT of chest A) No lung metastases B) Involvement of gallbladder and diaphragm allowed C) Involvement of omentum allowed D) Involvement of abdominal wall allowed E) Involvement of colon, stomach, duodenum excluded Exclusion Criteria: Unable to provide informed consent Age <18 years Unable to take anti-viral medication for hepatitis B Unable to take sorafenib Medically unfit for surgery Prior malignancy other than those specifically allowed by study Prior treatment of HCC Tumor characteristics A) HCC >10cm B) Bilobar tumor C) Mixed cholangiocarcinoma HCC D) Extra-hepatic tumor E) Tumor involving stomach, duodenum or colon F) Tumor involving hepatic veins or vena cava G) Tumor involving portal vein bifurcation Liver disease A) Liver function decompensated beyond Child's B7 B) Significant portal hypertension - splenomegaly, varices, ascites or platelet count <100,000 C) Co-infection with HBV and HCV D) Co-infection with HIV ECOG performance status >1

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surgery plus sorafenib<br>surgical resection followed by adjuvant sorafenib | Procedure: hepatic resection<br>* removal of portion of liver containing cancer<br>Drug: Sorafenib<br>* sorafenib either as adjuvant therapy after resection or as only treatment<br>|
| Active Comparator: sorafenib only<br>sorafenib only | Drug: Sorafenib<br>* sorafenib either as adjuvant therapy after resection or as only treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | time from randomization to death | 2-3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival | time from initiation of intervention until progression as defined by RESIST | 3-12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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portal vein invasion