Phase II SBRT & Chemo for Unresectable Cholangiocarcinoma Followed by Liver Transplantation

June 30, 2016 updated by: Daniel T. Chang, Stanford University

Phase II Study of Stereotactic Body Radiotherapy (SBRT) and Chemotherapy for Unresectable Cholangiocarcinoma Followed by Liver Transplantation

The purpose of this study is to determine progression-free survival at 12 months for stereotactic body radiotherapy (SBRT) and chemotherapy for unresectable hilar cholangiocarcinoma (CCA).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Investigators hope to learn more about neoadjuvant SBRT and chemotherapy for unresectable CCA, and if SBRT followed by chemotherapy can lead to successful liver transplantation. This knowledge is important for this patient group as this disease is a highly lethal malignancy that often presents as unresectable, however surgery or transplantation are the only curative options.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of cholangiocarcinoma by any of the below:

    • Positive transcatheter biopsy or brush cytology
    • CA 19-9 ≥ 100mg/mL with a malignant-appearing stricture on cholangiography
    • Biliary ploidy by fluorescent in situ hybridization with a malignant stricture on cholangiography
  • Liver tumors not to exceed 8 cm in greatest axial dimension (800 cc of uninvolved liver)
  • Unresectable tumor above cystic duct

  • Hepatic lesion in patients for whom surgical resection is not possible or would not result in an opportunity for cure by any of the below:

    • Bilateral segmental ductal extension
    • Encasement of the main portal vein
    • Unilateral segmental ductal extension with contralateral vascular encasement
    • Unilateral atrophy with either contralateral segmental ductal or vascular (hepatic artery, portal vein) involvement
  • Ascites is allowed if the Model for End-Stage Liver Disease (MELD) score is <15[1]
  • Age > 18 years old
  • Eastern Clinical Oncology Group performance status 0, 1 or 2 (Appendix 1)

  • Lab values within 2 wks prior to randomization:

    • See STUDY SCHEMA for specific blood count inclusion criteria: ANC ≥ 500 x 109/L (≥ 1500/mm3), Platelets ≥ 5 x 109/L (≥ 50,000/mm3), Hgb ≥ 9g/dL
    • Adequate liver function: Total bilirubin ≤1.5 x upper limit of normal (ULN); ALT and/or AST & alkaline phosphatase ≤ 5 x ULN.
    • Adequate biliary drainage, with no evidence of active uncontrolled infection (patients on antibiotics are eligible).
    • See STUDY SCHEMA for specific renal function inclusion criteria: Adequate renal function with a calculated GFR ≥ 40 ml/min. If the calculated GFR is below 40 ml/min a 24 hour urine creatinine clearance can be used.
    • Albumin > 2.5 mg/dL
    • INR ≤ 1.5
  • Life expectancy > 6 months
  • Capable of giving written informed consent

Exclusion Criteria:

  • Prior radiotherapy to the upper abdomen
  • Contraindication to receiving radiotherapy
  • Prior chemotherapy
  • Prior biliary resection or attempted resection
  • Prior transperitoneal biopsy
  • Large esophageal varices without band ligation
  • Active GI bleed or within 2 weeks of study enrollment
  • Ascites refractory to medical therapy or shunting
  • Active/unresolved biliary tract obstruction
  • Presence of multifocal, lymphatic, or extrahepatic metastases
  • Participation in another concurrent treatment protocol

  • If history of other primary cancer, subject eligible only if she or he has:

    • Curatively resected non-melanomatous skin cancer
    • Curatively treated cervical carcinoma in situ
    • Other primary solid tumor curatively treated with no known active disease present and no treatment administered for the last 3 years
  • Any evidence of severe or uncontrolled systemic diseases or laboratory finding that in the view of the investigator makes it undesirable for the patient to participate in the trial
  • Any psychiatric or other disorder (eg brain metastases) likely to impact on informed consent
  • Pregnancy or breast-feeding
  • While not excluded, patients with significant impaired hearing must be made aware of potential ototoxicity and may choose not to be included. If included, baseline audiograms are recommended and, in those given cisplatin, should be followed by repeat audiograms prior to cycle 2.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: SBRT, Chemo and Liver Transplantation
The patients received Stereotactic Body Radiotherapy and Chemotherapy followed by a liver transplantation. The chemo could be any combination of the following: Gemcitabine, Cisplatin, Carboplatin, Capecitabine and 5FU
Procedure: Stereotactic Body Radiotherapy
Standard of care
Other Names:
  • External photon radiation
Drug: Gemcitabine
100 mg/m2, IV
Other Names:
  • Gemzar
Drug: Cisplatin
25 mg/m2, IV
Other Names:
  • Platinol
  • Platinol-AQ
Drug: Carboplatin
AUC 2, based on Calvert formula, IV
Other Names:
  • Paraplatin
  • Paraplatin-AQ
Drug: Capecitabine
1000 mg/m2, PO
Other Names:
  • Xeloda
Drug: 5FU
200 mg/m2
Other Names:
  • Carac
  • Adrucil
  • Fluorouracil
  • Efudex
  • Fluoroplex
  • Efudix
Procedure: Liver transplantation

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression-free Survival at 12 Months
Time Frame: 12 months
Progression free survival is defined to be the time to progression of disease or death.
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pathologic Complete Response Rate
Time Frame: 12 months
Pathologic complete response will be defined as no residual tumor cells seen on the explanted liver specimen.
12 months
Serum CA 19-9 Levels
Time Frame: 12 months
Initial level of Cancer antigen 19-9
12 months
Overall Survival at 12 Months
Time Frame: 12 months
the estimated probability for the percentage of participants with overall survival at 12 months.
12 months
Liver Transplant Rate
Time Frame: 12 months
The number of patients receiving liver transplant among patients who initially have tumors ≤3 cm
12 months
Freedom From Local Progression at 12 Months
Time Frame: 12 months
the proportion of patients who experienced a local recurrence at 12 months with death as a competing risk
12 months
Liver Transplant Conversion Rate
Time Frame: 12 months
The ability to successfully perform liver transplant among patients who initially have tumor >3 cm
12 months
Median Time to Overall Survival
Time Frame: 18 months
The time to overall survival is defined as the time to death from any cause. The median was determined via Kaplan Meier methodology.
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Stanford University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 15, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 25, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 28, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 29, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 30, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HEP0032 (Other Identifier: Stanford University)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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