Phase I Trial of Radiation Therapy in Patients With Liver Cancers and Impaired Liver Function
Overview
- Phase
- Phase 1
- Intervention
- Survey Administration
- Conditions
- Cholangiocarcinoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Maximum dose constraint
- Status
- Active, Not Recruiting
- Last Updated
- 16 days ago
Overview
Brief Summary
This phase I trial studies the side effects and the best dose of radiation therapy in treating patients with hepatocellular carcinoma, cholangiocarcinoma, or cancer that has spread from the original (primary) tumor to the liver who also have impaired liver function (liver damage caused by cirrhosis, chemotherapy, or surgery). Radiation therapy (RT) uses high energy x-rays to kill tumor cells and shrink tumors. New methods of giving RT to the liver may help control cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the safety of high dose radiotherapy in patients who have liver tumors (hepatocellular carcinoma \[HCC\]/cholangiocarcinoma/liver metastases from any primary) and who have impaired liver function or low functional liver volume or who have received prior liver radiation. SECONDARY OBJECTIVES: I. To evaluate 2 year local control with radiotherapy in these patients. II. To evaluate tumor response, patterns of failure, and survival in these patients. III. To evaluate imaging- and serum-based biomarkers in these patients, as correlates of hepatic toxicity and tumor response. OUTLINE: This is a dose-escalation study. Patients undergo radiation therapy 5 days a week for a total of 15 or 25 fractions in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4-8 weeks and then every 3-4 months for 2 years. Patients who progress during the two year follow-up period are followed up every 6 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of hepatocellular carcinoma, cholangiocarcinoma, or liver metastasis from any histology
- •Patients may have single or multinodular tumors
- •There is no specific tumor size cut-off for this protocol; however, the radiation treatment plan must meet the protocol's dose constraints
- •Compromised liver function as defined by any of the following:
- •Cohort 1: Advanced cirrhosis group
- •Borderline Child-Pugh class A6
- •Child-Pugh class B
- •The patients in this advanced cirrhosis group must have at least 400 ml of functional liver, as estimated on either diagnostic imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]) or single photon emission computed tomography (SPECT)/CT with Tc-99m sulfur colloid; there is no upper limit on the functional liver volume for these patients
- •Cohort 2: Low functional liver volume without underlying chronic liver disease
- •Previous irinotecan or oxaliplatin chemotherapy
Exclusion Criteria
- •Prior liver-directed radiation therapy in cohort 1 (advanced cirrhosis group) or cohort 2 (low functional volume group)
- •Prior yttrium-90 therapy for patients in cohorts 1 or 2
- •Patients with a Child-Pugh score less than 6 or greater than 9 for radiation naive patients with cirrhosis (cohort 1)
- •Child-Pugh score of greater than 6 for patients with cirrhosis who previously received liver directed radiation (EBRT or Y90 RE) (cohort 3)
- •Unstable angina and/or symptomatic congestive heart failure requiring hospitalization within the last 6 months; transmural myocardial infarction within the last 6 months prior to study entry
- •Current evidence of fever or untreated infection
- •Active hepatitis, including but not limited to viral and drug-induced
- •Poorly controlled inflammatory bowel disease
- •Women with a positive pregnancy test
- •Inability to comply with study and/or follow-up procedures
Arms & Interventions
Treatment (radiation therapy)
Patients undergo radiation therapy 5 days a week for a total of 15 or 25 fractions in the absence of disease progression or unacceptable toxicity.
Intervention: Survey Administration
Treatment (radiation therapy)
Patients undergo radiation therapy 5 days a week for a total of 15 or 25 fractions in the absence of disease progression or unacceptable toxicity.
Intervention: Radiation Therapy
Treatment (radiation therapy)
Patients undergo radiation therapy 5 days a week for a total of 15 or 25 fractions in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Treatment (radiation therapy)
Patients undergo radiation therapy 5 days a week for a total of 15 or 25 fractions in the absence of disease progression or unacceptable toxicity.
Intervention: Magnetic Resonance Imaging
Outcomes
Primary Outcomes
Maximum dose constraint
Time Frame: 4-8 weeks after completion of radiation therapy
Defined as the highest level dose constraint at which no more than 1 of 6 evaluable patients has had a dose limiting toxicity. Toxicities will be summarized with frequency by type, severity and their relationship to the treatment.
Secondary Outcomes
- Tumor response(Up to 2 years)
- Patterns of failure(Up to 2 years)
- Overall survival(Up to 2 years)
- Local disease control rate(Up to 2 years)