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Sorafenib-RT in Treating Hepatocellular Carcinoma (SHEP)

Primary Purpose

Hepatocellular Carcinoma

Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Sorafenib
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Sorafenib, Hepatocellular carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must have HCC either

    • confirmed pathologically
    • diagnosed by showing vascular enhancement of the lesion on at least two imaging techniques
    • diagnosed by showing vascular enhancement on a single technique if the AFP is over 200, in the setting of cirrhosis or chronic hepatitis B without cirrhosis. Biopsies are mandatory (unless an absolute contraindication exists).
  • The tumour must be unresectable or medically inoperable
  • At least 800 cc of non-tumor liver
  • Patients must be > 4 weeks since any major surgery.
  • Patients may have had previous systemic treatment (with at least a 2 week break from systemic therapy to start of radiation therapy. Prior sorafenib or any other targeted therapy with anti-VEGF activity is not permitted.
  • Child-Pugh Liver score A
  • Barcelona-Clinic Liver Cancer (BCLC) score A or B or C (BCLC C permitted if ECOG 0-1 and Child Pugh A, with portal invasion)
  • Age 18 years or older.
  • Life expectancy of equal to or greater than 3 months.
  • ECOG performance status 0-1.
  • Patients must have normal organ and marrow function.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Negative pregnancy test for women of child bearing age
  • If the patient has a history of varices and portal hypertension, elective treatment (e.g. banding) of varices will be performed prior to start of radiation therapy.
  • The effects of Sorafenib on the developing human fetus are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.

Exclusion Criteria:

  • Serious medical conditions that might be aggravated by treatment, including but not limited to: myocardial infarction within 6 months, congestive heart failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled psychotic disorders, serious infections, active peptic ulcer disease, active hepatitis or cerebrovascular disease with previous stroke within the past 12 months.
  • Patients may not be receiving any other investigational agents concurrently or within 2 weeks of initiation of treatment.
  • Pregnant women
  • Patients with immune deficiency
  • Ascites (on imaging or clinical exam).
  • Prior liver or upper abdomen radiation therapy.
  • Resectable hepatocellular carcinoma.
  • Thrombolytic therapy within 4 weeks, or any concurrent anti-coagulant therapy.
  • Uncontrolled hypertension
  • Patients with other active malignancies
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib.
  • Patients with active hepatitis or encephalopathy related to liver failure.
  • Patients with any bleeding or clotting disorder.
  • Patients with unhealed wounds or ulcers.
  • Prior sorafenib treatment is not permitted.
  • Patient with nausea and vomiting refractory to medical therapies, significant prior bowel resection, and inflammatory bowel disease.
  • Patients with evidence of extrahepatic metastases
  • Patients on Rifampin, St.John's Wort, Phenytonin, Carbamazepine, Phenobarbital, or chronic use (more than 4 weeks) of dexamethasone.

Sites / Locations

  • University Health Network

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sorafenib + RT

Arm Description

Outcomes

Primary Outcome Measures

Determine the MTD of sorafenib and RT in patients with hepatocellular carcinoma using an iso-toxicity radiation dose allocation scheme. Determine the acute toxicity (< 3 months) of sorafenib when combined with RT.

Secondary Outcome Measures

Determine late toxicities, in-field local control at 3 months, overall survival, progression time, and progression free survival. Quantify alteration in perfusion parameters.Assess serum and tissue biomarkers. Assess quality of life in these patients.

Full Information

First Posted
May 1, 2009
Last Updated
October 4, 2021
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT00892658
Brief Title
Sorafenib-RT in Treating Hepatocellular Carcinoma (SHEP)
Official Title
A Phase I Study of Sorafenib and Radiation Therapy in Patients With Hepatocellular Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
January 2009 (Actual)
Primary Completion Date
November 2019 (Actual)
Study Completion Date
December 16, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The incidence is highest in Asia and it is increasing in North America, with a two to three fold increase in mortality in North America expected over the next two decades. Previous research has shown that tumours often have abnormal blood vessels that may reduce the effect of radiation therapy. New drugs, known as "anti-angiogenic" drugs have been shown in animal and human studies to damage or change tumour blood vessels in ways that may make tumors more sensitive to radiation treatment. 38-44 patients diagnosed with HCC will be invited to take part in this study. Upon completion, this study will establish the safety of the combination of radiation and sorafenib in patients with HCC. This will also establish preliminary data regarding efficacy of the combination and investigate potential imaging and serum/tissue markers surrogates for tumor response and/or drug activity.
Detailed Description
The study design will include 2 radiation strata of patients, with a constant radiation dose for strata 1 requiring a low volume of liver to be irradiated, and a variable dose defined based on the effective liver volume irradiated in the second strata, which will require more liver volume to be irradiated, based on our prior experience. Both stratas one and two will be accrued concurrently. Biologic response will be assessed using standard contrast CT scans. Correlative studies of biological markers, perfusion CT, and microbubble contrast enhanced ultrasound will also be performed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Sorafenib, Hepatocellular carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sorafenib + RT
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Intervention Description
Patients will receive sorafenib alone (following the dose escalation scheme) for one week, followed by 2 weeks of concurrent administration of sorafenib with conformal radiation therapy (6 fractions over two weeks). Sorafenib administration will continue for four weeks following completion of radiation. At three months following radiation, when liver toxicity is assessed, full dose sorafenib (400mg PO BID) will then be initiated and continued until disease progression or serious toxicity occurs, to a maximum time of 12 months.
Primary Outcome Measure Information:
Title
Determine the MTD of sorafenib and RT in patients with hepatocellular carcinoma using an iso-toxicity radiation dose allocation scheme. Determine the acute toxicity (< 3 months) of sorafenib when combined with RT.
Time Frame
1 year enrollment; 5 years follow-up
Secondary Outcome Measure Information:
Title
Determine late toxicities, in-field local control at 3 months, overall survival, progression time, and progression free survival. Quantify alteration in perfusion parameters.Assess serum and tissue biomarkers. Assess quality of life in these patients.
Time Frame
1 year enrollment; 5 years follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have HCC either confirmed pathologically diagnosed by showing vascular enhancement of the lesion on at least two imaging techniques diagnosed by showing vascular enhancement on a single technique if the AFP is over 200, in the setting of cirrhosis or chronic hepatitis B without cirrhosis. Biopsies are mandatory (unless an absolute contraindication exists). The tumour must be unresectable or medically inoperable At least 800 cc of non-tumor liver Patients must be > 4 weeks since any major surgery. Patients may have had previous systemic treatment (with at least a 2 week break from systemic therapy to start of radiation therapy. Prior sorafenib or any other targeted therapy with anti-VEGF activity is not permitted. Child-Pugh Liver score A Barcelona-Clinic Liver Cancer (BCLC) score A or B or C (BCLC C permitted if ECOG 0-1 and Child Pugh A, with portal invasion) Age 18 years or older. Life expectancy of equal to or greater than 3 months. ECOG performance status 0-1. Patients must have normal organ and marrow function. Ability to understand and the willingness to sign a written informed consent document. Negative pregnancy test for women of child bearing age If the patient has a history of varices and portal hypertension, elective treatment (e.g. banding) of varices will be performed prior to start of radiation therapy. The effects of Sorafenib on the developing human fetus are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Exclusion Criteria: Serious medical conditions that might be aggravated by treatment, including but not limited to: myocardial infarction within 6 months, congestive heart failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled psychotic disorders, serious infections, active peptic ulcer disease, active hepatitis or cerebrovascular disease with previous stroke within the past 12 months. Patients may not be receiving any other investigational agents concurrently or within 2 weeks of initiation of treatment. Pregnant women Patients with immune deficiency Ascites (on imaging or clinical exam). Prior liver or upper abdomen radiation therapy. Resectable hepatocellular carcinoma. Thrombolytic therapy within 4 weeks, or any concurrent anti-coagulant therapy. Uncontrolled hypertension Patients with other active malignancies History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib. Patients with active hepatitis or encephalopathy related to liver failure. Patients with any bleeding or clotting disorder. Patients with unhealed wounds or ulcers. Prior sorafenib treatment is not permitted. Patient with nausea and vomiting refractory to medical therapies, significant prior bowel resection, and inflammatory bowel disease. Patients with evidence of extrahepatic metastases Patients on Rifampin, St.John's Wort, Phenytonin, Carbamazepine, Phenobarbital, or chronic use (more than 4 weeks) of dexamethasone.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Laura Dawson, MD
Organizational Affiliation
University Health Network, Princess Margaret Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anthony Brade, MD
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

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Sorafenib-RT in Treating Hepatocellular Carcinoma (SHEP)

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