Sorafenib-RT in Treating Hepatocellular Carcinoma (SHEP)

NCT00892658 | Completed Phase 1 DMC

• 1 other identifier: UHN REB 08-0761-C
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatocellular Carcinoma

Keywords

Sorafenib; Hepatocellular carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  1 year enrollment; 5 years follow-up

Secondary Outcomes (1)

• 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.

  1 year enrollment; 5 years follow-up

Study Arms (1)

Sorafenib + RT

EXPERIMENTAL

Drug: Sorafenib

Interventions

Sorafenib DRUG

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.

Sorafenib + RT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Laura Dawson, MD

  University Health Network, Princess Margaret Hospital

  PRINCIPAL INVESTIGATOR

• Anthony Brade, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2009
• First Posted: May 4, 2009
• Study Start: January 1, 2009
• Primary Completion: November 1, 2019
• Study Completion: December 16, 2020
• Last Updated: October 6, 2021

Record last verified: 2021-10

Locations

CA (1)