A Pilot Study of Trans Arterial Chemoembolization (TACE), Followed by Stereotactic Radiation Therapy (SBRT) for Patients With Hepatocellular Carcinoma

Hepatocellular Carcinoma (HCC) Clinical Trial

— RAD 0902  

Official title:

RAD 0902: A Pilot Study of Trans Arterial Chemoembolization (TACE), Followed by Stereotactic Radiation Therapy (SBRT) for Patients With Hepatocellular Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01247298
• Other study ID #: F100708009
• Status: Completed
• Phase: Phase 0
• First received: November 22, 2010
• Last updated: December 16, 2016
• Start date: October 2010
• Est. completion date: December 2016

Study information

• Verified date: December 2016
• Source: University of Alabama at Birmingham
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This investigational study will evaluate if using a combination of TACE along with high dose SBRT would show improvement in local control in patients with Hepatocellular Carcinoma.

Description:

Primary objectives of this research

1. Evaluate the safety of a combination of TACE and high dose SBRT

2. Measure time to progression (TTP) and local recurrence rate of HCC treated with a combination of TACE & SBRT.

Secondary objectives of this research

1. Assess failure patterns and survival of patients treated with TACE & SBRT.

2. Analyze dose volume characteristics that influence Radiation Induced Liver Disease (RILD) among patients treated with a combination of TACE and SBRT.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

Diagnosis

Patients meeting all the following criteria will be considered for enrollment:

• Pathologically confirmed HCC -OR

• HCC greater than 2 cm with classic radiographic findings on 2 separate testing modalities, or an HCC greater than 2 cm with a serum alpha feto-protein greater than 200.

Lesions:

Single liver lesion: measuring 3 cm to = 8 cm*.

• Multiple liver lesions: = 3 liver lesions, none measuring over 5 cm, provided all lesions are considered for TACE.

• Lesions <3 cm if they are in an unfavorable location for ablation† *The size criteria of hepatic lesions are also subjected to the dose volume constraints for radiotherapy, as described below.

Patient

• Patient deemed to not be a liver transplant candidate at the time of study entry(or refuse transplant).

• Patient deemed to not be a candidate for surgical resection at the time of study entry (or refuse surgical resection).

• Patient deemed to not be a candidate for ablation (or refuse ablation therapy).

• Patient must be a candidate and receive TACE.

• ECOG (Eastern Cooperative Oncology Group) Zubrod Performance Scale = 0-1.

• Age > 19

• Patient should not be pregnant. Women of childbearing potential and male participants must practice adequate contraception.

Adequate organ function as evidence by:

Hematology

• Absolute neutrophil count (ANC) > 1,200 cells/mm3 < 2 weeks prior to entry

• Platelets > 40,000 cells/mm3 < 2 weeks prior to entry into study

• Hemoglobin > 8 g/dl < 2 weeks prior to entry into study

Liver Functions

• Bilirubin should be < 2 times the normal limit, INR should be <2, and liver enzymes less than 3 times the normal limits drawn within 2 weeks prior to study entry.

• Patients who have developed a tumor recurrence following a liver transplant, liver resection or liver ablation are eligible for this study.

• Patients with Child Pugh Class A & B disease are eligible for the study; Class C patients are ineligible. Patients with normal liver function or compensated cirrhosis are eligible for the study. However, patients with poorly controlled ascites are ineligible for the study (see below).

• Patients with clinically significant liver failure are ineligible.

• Underlying liver cirrhosis is not a contraindication for entry, but should be recorded for analysis of relationship to toxicity development.

Signed informed consent document

Male or female patients of any ethnic group. Female patients must be surgically sterile, postmenopausal (no menses for at least one year), or using medically approved method of contraception. Men must agree to use a medically approved method of contraception.

Age > 19 years.

Imaging must be completed within 60 days prior to study entry. CT Simulation images may be used for both Liver and Chest imaging given that image includes the chest and the Radiation Oncologists reviews and comments on chest imaging.

Patient must be evaluated by a radiation oncologist within 2 weeks prior to study entry.

Exclusion Criteria:

Patients presenting with any of the following will not be included in the study:

1. Prior invasive malignancies are ineligible, unless patients are free of disease for over 5 years. For example a patient cannot be registered for this study for treatment of HCC, if there is a history of prior colorectal cancer. (Patients with non-melanoma skin cancer or in situ cancers of the breast, oral cavity, or cervix are eligible).

2. Prior radiotherapy to the liver or surrounding areas that would result in overlap of radiation therapy fields is an ineligibility criterion. Patients with other known contraindications to radiation including systemic sclerosis, ulcerative colitis etc. also are ineligible.

3. Systemic therapy using any chemotherapy and/or targeted agents given within 2 weeks prior to TACE, during RT, and / or within 3 weeks following RT completion are grounds for exclusion. Patients who received Bevacizumab or other vascular endothelial growth factor antagonists 2 months prior or following TACE/ RT are ineligible. Administration of Anthracyclines or other chemotherapy agents with dominant hepatotoxicity within 8 weeks of completion of RT is also an exclusion criterion.

4. Severe co-morbidity including (but not restricted to) unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months, transmural myocardial infarction within the last 6 months, uncontrolled arterial hypertension, uncontrolled diabetes mellitus, dementia, acute infections (bacterial, fungal or HIV infection requiring oral or intravenous antibiotics at the time of registration, severe chronic airway disease (COPD) other serious illness requiring hospitalization or precluding study therapy at the time of registration are contraindications.

5. Patients who are receiving anticoagulation treatment with Coumadin or IV heparin (including anticoagulation to maintain central line) resulting in INR (international normalized ratio) > 2 times upper level normal are ineligible.

6. Uncontrolled or symptomatic clinical ascites makes patient ineligible for the study.

7. Major surgical procedure within 3 weeks prior to study entry.

8. History of hypersensitivity to chemotherapy agents, contrast material.

9. Pregnancy, breast-feeding or planning to become pregnant.

10. Treatment with any investigational product in the last 4 weeks before study entry.

11. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.

Patients of Reproductive Potential

The patient must not be pregnant or breast-feeding at enrollment in the study. Absence of pregnancy must be demonstrated by serum or urine testing prior to enrollment into the study.

Female patients of child bearing potential (i.e., ovulating, premenopausal, not surgical sterile) must use a medically accepted contraceptive regimen. Male patients must agree to use a medically approved method of contraception.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma (HCC)

Intervention

Procedure:
• Trans- Arterial Chemoembolization
TACE has been used extensively in the palliative treatment of hepatocellular carcinoma (HCC). This treatment involves accessing the major feeder artery to the liver tumor using a catheter passed through the femoral artery in the groin. This procedure is performed by the Interventional Radiologist. Once access is established, chemotherapy drugs and contrast material are injected directly into the tumor. This procedure is performed under sedation and does not usually require hospital stay. Patient will be given antiemetics (medication to stop or prevent nausea/vomiting), antibiotics, and pain relievers after the procedure, which patient may be asked to continue for several hours.
• Stereotactic Body Radiation Therapy (SBRT)
SRT(Stereotactic Radiation Therapy)is a technique of high precision radiation treatment.Liver is one of the body sites where SRT has been successfully used. During SBRT, patient will be asked to lie still on a treatment bed under the radiation machine.The physician uses sophisticated computers to direct the radiation beam to the tumor with great accuracy.The radiation physician will prescribe antiemetics before the treatment starts.Patient will not experience any pain or other side-effects during treatment, but may feel uncomfortable lying still for several minutes.A typical SBRT treatment may last 30 mins and there will be three treatments.Patient will be alone in treatment room, however they are constantly monitored throughout the procedure.They can communicate with the physician and technicians outside the room using a intercom.Patient will be able to listen to music during the procedure.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Outcome	Evaluate the safety of a combination of TACE and high dose SBRT; Measure time to progression (TTP) and local recurrence rate of HCC treated with a combination of TACE & SBRT.	length of study treatment is up to 45 day after completing TACE treatment. Patient will be asked to visit their study doctor for follow-up exams every 3 months for 2 years while participating in this study.	Yes
Secondary	Secondary Outcome	Assess failure patterns and survival of patients treated with TACE & SBRT.; Analyze dose volume characteristics that influence Radiation Induced Liver Disease (RILD) among patients treated with a combination of TACE and SBRT.	up to 2 years after treatment completed	Yes