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

NCT ID: NCT02626312

Last Updated: 2025-10-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-15
• Study Completion Date: 2026-04-28

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.

Conditions

Cholangiocarcinoma; Cirrhosis; Hepatocellular Carcinoma; Metastatic Malignant Neoplasm in the Liver

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Correlative studies

Radiation Therapy

Intervention Type: RADIATION

Undergo radiation therapy

Survey Administration

Intervention Type: OTHER

Ancillary studies

Interventions

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Magnetic Resonance Imaging

Correlative studies

Intervention Type: PROCEDURE

Radiation Therapy

Undergo radiation therapy

Intervention Type: RADIATION

Survey Administration

Ancillary studies

Intervention Type: OTHER

Other Intervention Names

Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MRI; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Cancer Radiotherapy; Irradiate; Irradiated; irradiation; Radiation; Radiotherapeutics; RADIOTHERAPY; RT; Therapy, Radiation

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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eugene J Koay

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Chang E, Wong FCL, Chasen BA, Erwin WD, Das P, Holliday EB, Koong AC, Ludmir EB, Minsky BD, Noticewala SS, Smith GL, Taniguchi CM, Rodriguez MJ, Beddar S, Martin-Paulpeter RM, Niedzielski JS, Sawakuchi GO, Schueler E, Perles LA, Xiao L, Szklaruk J, Park PC, Dasari AN, Kaseb AO, Kee BK, Lee SS, Overman MJ, Willis JA, Wolff RA, Tzeng CD, Vauthey JN, Koay EJ. Phase I trial of single-photon emission computed tomography-guided liver-directed radiotherapy for patients with low functional liver volume. JNCI Cancer Spectr. 2024 Apr 30;8(3):pkae037. doi: 10.1093/jncics/pkae037.

Reference Type: DERIVED

PMID: 38730548 (View on PubMed)

Other Identifiers

P30CA016672

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2016-00006

Identifier Type: REGISTRY

Identifier Source: secondary_id

2015-0052

Identifier Type: OTHER

Identifier Source: secondary_id

2015-0052

Identifier Type: -

Identifier Source: org_study_id