Radiation Therapy in Treating Patients With Hepatocellular Carcinoma, Cholangiocarcinoma, or Liver Metastasis Who Have Impaired Liver Function

M.D. Anderson Cancer Center

Status and phase

Active, not recruiting

Phase 1

Conditions

Cirrhosis

Metastatic Malignant Neoplasm in the Liver

Hepatocellular Carcinoma

Cholangiocarcinoma

Treatments

Other: Laboratory Biomarker Analysis

Procedure: Magnetic Resonance Imaging

Radiation: Radiation Therapy

Other: Survey Administration

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT02626312

NCI-2016-00006 (Registry Identifier)

P30CA016672 (U.S. NIH Grant/Contract)

2015-0052 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

36 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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
  - Previous liver resection(s)
    - These patients must have at least 400 ml of functional liver, as estimated by either diagnostic imaging computed tomography or magnetic resonance imaging (CT or MRI) or SPECT/CT with Tc-99m sulfur colloid; there is no upper limit on the functional liver volume for these patients;
- Cohort 3: History of prior liver-directed radiation therapy with either fractionated external beam radiation therapy (EBRT), stereotactic body radiation therapy (SBRT) or yttrium-90 radioembolization (Y90 RE); the interval between prior EBRT and re-irradiation on protocol should be equal to or greater than 12 months; the interval between prior Y90 RE and re-irradiation on protocol should be equal to or greater than 6 months;
  - Cirrhosis group:
    - Child-Pugh class A5;
    - Borderline Child-Pugh class A6;
    - The patients in this group must have at least 400 ml of functional liver, as estimated on either diagnostic imaging (CT or MRI) or SPECT/CT with Tc-99m sulfur colloid; there is no upper limit on the functional liver volume for these patients
- Low functional liver volume without underlying liver disease
  - Previous irinotecan or oxaliplatin chemotherapy
  - Previous liver resection(s)
  - These patients must have at least 400 ml of functional liver, as estimated by either diagnostic imaging (CT or MRI) or SPECT/CT with Tc-99m sulfur colloid; there is no upper limit on the functional liver volume for these patients
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
Women of childbearing potential (those who have not undergone a hysterectomy or who have not been postmenopausal for at least 24 consecutive months) must agree to practice adequate contraception and to refrain from breast feeding
Prior history of surgical resection, chemotherapy, transarterial chemoembolization (TACE), and/or radiofrequency ablation are allowed
Expected survival must be greater than 3 months
Patients may receive concurrent capecitabine or sorafenib at the discretion of the treating physicians
Signed study-specific consent form

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
Patients with an active second malignancy or prior invasive malignancy unless disease free for a minimum of 3 years; non-melanoma skin cancer and previous early prostate cancer that had a non-rising prostate-specific antigen (PSA) can be enrolled