Sorafenib-RT in Treating Hepatocellular Carcinoma - Full Text View

Sponsored by:	University Health Network, Toronto
Information provided by:	University Health Network, Toronto
ClinicalTrials.gov Identifier:	NCT00892658

Purpose

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.

Condition	Intervention	Phase
Hepatocellular Carcinoma	Drug: Sorafenib	Phase I

MedlinePlus related topics: Cancer Radiation Therapy

Drug Information available for: Sorafenib Sorafenib tosylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase I Study of Sorafenib and Radiation Therapy in Patients With Hepatocellular Carcinoma

Further study details as provided by University Health Network, Toronto:

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. [ Time Frame: 1 year enrollment; 5 years follow-up ] [ Designated as safety issue: Yes ]

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. [ Time Frame: 1 year enrollment; 5 years follow-up ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	44
Study Start Date:	January 2009
Estimated Study Completion Date:	January 2015
Estimated Primary Completion Date:	January 2015 (Final data collection date for primary outcome measure)

Intervention Details:

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.

Detailed Description:

As part of this study, patients will receive sorafenib alone (at escalating doses 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 the study dose. At three months following radiation, when liver toxicity is assessed and is absent, 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.

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. The first strata will be planned to be completed prior to the second strata. 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)
Child-Pugh Liver score A
Barcelona-Clinic Liver Cancer (BCLC) score A or B
Age 18 years or older.
Life expectancy of greater than 3 months.
ECOG performance status 0.
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

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00892658

Contacts

Contact: Laura Dawson, MD

416 946 4501 ext 2125

laura.dawson@rmp.uhn.on.ca

Locations

Canada, Ontario
University Health Network	Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Laura Dawson, MD 416 946 4501 ext 2125 laura.dawson@rmp.uhn.on.ca
Principal Investigator: Laura Dawson, MD

Sponsors and Collaborators

University Health Network, Toronto

Investigators

Principal Investigator:

Laura Dawson, MD

University Health Network, Princess Margaret Hospital

More Information

No publications provided

Responsible Party:	University Health Network, Research Ethics Board ( Dr. Laura Dawson, Staff Radiation Oncology, Clinician Scientist )
Study ID Numbers:	UHN REB 08-0761-C
Study First Received:	May 1, 2009
Last Updated:	May 1, 2009
ClinicalTrials.gov Identifier:	NCT00892658 History of Changes
Health Authority:	Canada: Ethics Review Committee

Keywords provided by University Health Network, Toronto:

Sorafenib
Hepatocellular carcinoma

Study placed in the following topic categories:

Liver Neoplasms
Liver Diseases
Digestive System Diseases
Digestive System Neoplasms
Carcinoma, Hepatocellular
Gastrointestinal Neoplasms

Hepatocellular Carcinoma
Adenocarcinoma
Protein Kinase Inhibitors
Sorafenib
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Liver Diseases
Neoplasms by Histologic Type
Digestive System Neoplasms
Molecular Mechanisms of Pharmacological Action
Carcinoma, Hepatocellular
Antineoplastic Agents
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

Carcinoma
Liver Neoplasms
Neoplasms
Neoplasms by Site
Digestive System Diseases
Therapeutic Uses
Adenocarcinoma
Sorafenib
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on May 07, 2009