Brief Title
Radiation Therapy in Treating Patients With Hepatocellular Carcinoma, Cholangiocarcinoma, or Liver Metastasis Who Have Impaired Liver Function
Official Title
Phase I Trial of Radiation Therapy in Patients With Liver Cancers and Impaired Liver Function
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Maximum dose constraint
Secondary Outcome
Local disease control rate
Condition
Cholangiocarcinoma
Intervention
Laboratory Biomarker Analysis
Study Arms / Comparison Groups
Treatment (radiation therapy)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Other
Estimated Enrollment
88
Start Date
February 15, 2016
Primary Completion Date
February 28, 2022
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Eugene J Koay, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02626312
Organization ID
2015-0052
Secondary IDs
NCI-2016-00006
Responsible Party
Sponsor
Study Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Eugene J Koay, Principal Investigator, M.D. Anderson Cancer Center
Verification Date
June 2021