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

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ClinicalTrials.gov Identifier: NCT02626312
Recruitment Status : Recruiting
First Posted : December 10, 2015
Last Update Posted : August 6, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
Cholangiocarcinoma Cirrhosis Hepatocellular Carcinoma Metastatic Malignant Neoplasm in the Liver Other: Laboratory Biomarker Analysis Procedure: Magnetic Resonance Imaging Radiation: Radiation Therapy Other: Survey Administration Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 88 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Trial of Radiation Therapy in Patients With Liver Cancers and Impaired Liver Function
Actual Study Start Date : February 15, 2016
Estimated Primary Completion Date : February 28, 2022


Arm Intervention/treatment
Experimental: 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.
Other: Laboratory Biomarker Analysis
Correlative studies

Procedure: Magnetic Resonance Imaging
Correlative studies
Other Names:
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MRI
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging

Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • irradiation
  • Radiation
  • Radiotherapeutics
  • RADIOTHERAPY
  • RT
  • Therapy, Radiation

Other: Survey Administration
Ancillary studies




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Local disease control rate [ Time Frame: Up to 2 years ]
    The Kaplan Meier method will be used to estimate 2-year local disease control rate.

  2. Tumor response [ Time Frame: Up to 2 years ]
    Will be observed.

  3. Patterns of failure [ Time Frame: Up to 2 years ]
    Will be observed.

  4. Overall survival [ Time Frame: Up to 2 years ]
    The Kaplan Meier method will be used to estimate the probability of overall survival.


Other Outcome Measures:
  1. Tumor biomarker expression in serum [ Time Frame: Baseline ]
    Imaging- and serum-based biomarkers will be correlated with hepatic toxicity and tumor response. Plots such as box plot and scatter plots will be used to evaluate expressions of markers between patients with and without response, and between patients having experienced DLTs and patients having not experienced DLTs, and Wilcoxon rank sum test will be used to compare expressions of markers between these patients.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02626312


Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Eugene J. Koay    713-563-2300    ekoay@mdanderson.org   
Principal Investigator: Eugene J. Koay         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Eugene J Koay M.D. Anderson Cancer Center

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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02626312     History of Changes
Other Study ID Numbers: 2015-0052
NCI-2016-00006 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2015-0052 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
R01CA221971 ( U.S. NIH Grant/Contract )
First Posted: December 10, 2015    Key Record Dates
Last Update Posted: August 6, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Cholangiocarcinoma
Neoplasms, Second Primary
Liver Neoplasms
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Carcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Digestive System Diseases
Liver Diseases