Clinical trial NCT02626312: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Cholangiocarcinoma
Cirrhosis
Hepatocellular Carcinoma
Metastatic Malignant Neoplasm in the Liver
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2015-12-10
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximum dose constraint
timeFrame: 4-8 weeks after completion of radiation therapy
Secondary outcomes:
measure: Local disease control rate
timeFrame: Up to 2 years
measure: Tumor response
timeFrame: Up to 2 years
measure: Patterns of failure
timeFrame: Up to 2 years
measure: Overall survival
timeFrame: Up to 2 years
Other outcomes:
measure: Tumor biomarker expression in serum
timeFrame: Baseline
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Eugene J Koay
role: PRINCIPAL_INVESTIGATOR
References: