A Phase Ib Study of Stereotactic Radiotherapy (SBRT) Plus Sorafenib in Patients With Unresectable Hepatocellular Carcinoma (HCC)

Indiana University1 site in 1 countryFebruary 2012

ConditionsHepatocellular Carcinoma

InterventionsSorafenib Stereotactic radiotherapy

DrugsSorafenib

Overview

Phase: Phase 1
Intervention: Sorafenib
Conditions: Hepatocellular Carcinoma
Sponsor: Indiana University
Locations: 1
Primary Endpoint: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Status: Withdrawn
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a research study of a radiation treatment called stereotactic body radiotherapy (SBRT) plus a medicine called sorafenib. The purpose of this study is to evaluate the safety of SBRT plus Sorafenib to see what effects (good and bad) it has on the treatment of liver cancer.

Registry

clinicaltrials.gov

Start Date

February 2012

End Date

October 2014

Last Updated

11 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Indiana University

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•4.1.1Age ≥ 18 years. 4.1.2 Patients with HCC without cirrhosis or with CTP class A (maximum score 6).
•4.1.3 Patient must not be a surgical candidate at presentation. 4.1.4 Able to undergo contrast enhanced MRI of the primary tumor using the liver MRI protocol.
•4.1.5 Measurable disease per mRECIST criteria defined as lesions \>/=1cm showing intratumoral arterial enhancement in contrast-enhanced CT or MRI and being suitable for repeat measurements.
•4.1.6 Must not have evidence of metastatic disease. 4.1.7 Karnofsky performance status \>/=70% 4.1.8 Life expectancy ≥ 3 months as determined by the treating physician. 4.1.9 If single tumor, maximum tumor diameter must be \</= 6 cm. 4.1.10 No more than three discrete liver lesions, with the overall sum of diameters being \</= 6 cm.
•4.1.11 None of the lesions to be treated can be in closer than 0.5 cm to the wall of the stomach, duodenum, or hepatic flexure of the colon.
•4.1.12 Radiotherapy treatment planning confirms one of the following:
•One third of the uninvolved liver should receive \</=10 Gy
•At least 500 cc of uninvolved liver should receive \</=7 Gy 4.1.13 Radiotherapy treatment planning confirms all of the following parameters for other normal tissues tolerance:
•Maximal cord dose: 600 cGy per fraction x3 for a total of 18 Gy.
•Right kidney: \<2/3 of the kidney volume receives \> 15 Gy total dose and

Exclusion Criteria

•4.2.1 Medical history of systemic lupus erythematous, rheumatoid arthritis, systemic sclerosis or scleroderma.
•4.2.2 Prior radiation therapy to the abdomen 4.2.3 Prior treatment with Sorafenib or other Ras or VEGF pathway inhibitor. 4.2.4 Minor surgical procedure (e.g fine needle aspiration or needle biopsy) within 7 days of study registration.
•4.2.5 Major surgical procedure, significant traumatic injury, or serious non-healing wound, ulcer or bone fracture within 21 days of study registration; investigator has to document adequate healing has occurred prior to study registration.
•4.2.6 Any of the following within 6 months prior to study drug administration: severe/unstable angina (angina symptoms at rest), new onset angina (began within the last 3 months) or myocardial infarction, congestive heart failure, cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
•4.2.7 History of thrombotic or embolic events such as cerebrovascular accident or transient ischemic attack within the past 6 months.
•4.2.8 History of aneurysm or arteriovenous malformation. 4.2.9 Active, clinically serious infection \>/= CTCAE grade
•4.2.10 Receipt of any investigational agent within 4 weeks of study registration.
•4.2.11 Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management 4.2.12 Pulmonary hemorrhage/bleeding event ≥CTCAE Grade 2 within 4 weeks of study registration 4.2.13 Any other hemorrhage/bleeding event including esophageal variceal bleeding \>/= CTCAE Grade 3 within 4 weeks of study registration.
•4.2.14 Evidence or history of bleeding diathesis or coagulopathy 4.2.15 Chronic, daily treatment with nonsteroidal anti-inflammatory medications. (Daily aspirin use is permitted) 4.2.16 Use of carbamazepine (Carbatrol, Epitol, Equetro, Tegretol), rifabutin (Mycobutin), rifampin/ rifampicin (Rifadin, Rimactane), or ritonavir (Norvir).
•4.2.17 Known or suspected allergy to Sorafenib or any agent given in the course of this trial.

Arms & Interventions

Sorafenib plus Stereotactic Radiotherapy

Single agent Sorafenib x 2 weeks followed by Stereotactic Radiotherapy, then Sorafenib until disease progression.

Intervention: Sorafenib

Sorafenib plus Stereotactic Radiotherapy

Single agent Sorafenib x 2 weeks followed by Stereotactic Radiotherapy, then Sorafenib until disease progression.

Intervention: Stereotactic radiotherapy

Outcomes

Primary Outcomes

Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Time Frame: Start of sorafenib through disease progression, an expected average of 12 months.

Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Secondary Outcomes

Number of patients with local response(Start of sorafenib through disease progression, an expected average of 12 months)
Time from the start of the treatment until the criteria for overall disease progression is met or death occurs.(Start of sorafenib through disease progression, an expected average of 12 months.)
Time from start of treatment until death from any cause or date of last patient contact.(Start of soafenib until death.)