Clinical Trials /

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

NCT03971201

Description:

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.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: WPH20190507
  • NCT ID: NCT03971201

Conditions

  • Hepatocellular Cancer

Interventions

DrugSynonymsArms
SorafenibSurgery plus sorafenib

Purpose

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

      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
    

Trial Arms

NameTypeDescriptionInterventions
Surgery plus sorafenibExperimentalsurgical resection followed by adjuvant sorafenib
  • Sorafenib
sorafenib onlyActive Comparatorsorafenib only
  • Sorafenib

Eligibility Criteria

        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

          1. Arterial enhancement

          2. Venous washout

          3. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:overall survival
Time Frame:2-3 year
Safety Issue:
Description:time from randomization to death

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:White Plains Hospital

Trial Keywords

  • portal vein invasion

Last Updated

June 5, 2019