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

This study has been terminated.
(Poor accrual)
Sponsor:
Information provided by (Responsible Party):
Daniel T. Chang, Stanford University
ClinicalTrials.gov Identifier:
NCT01151761
First received: June 15, 2010
Last updated: June 30, 2016
Last verified: June 2016
  Purpose
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).

Condition Intervention Phase
Cholangiocarcinoma
Hepatobiliary Neoplasm
Liver Cancer
Bile Duct Cancer
Cancer of Gallbladder
Procedure: Stereotactic Body Radiotherapy
Drug: Gemcitabine
Drug: Cisplatin
Drug: Carboplatin
Drug: Capecitabine
Drug: 5FU
Procedure: Liver transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Stereotactic Body Radiotherapy (SBRT) and Chemotherapy for Unresectable Cholangiocarcinoma Followed by Liver Transplantation

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Progression-free Survival at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Progression free survival is defined to be the time to progression of disease or death.


Secondary Outcome Measures:
  • Pathologic Complete Response Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Pathologic complete response will be defined as no residual tumor cells seen on the explanted liver specimen.

  • Serum CA 19-9 Levels [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Initial level of Cancer antigen 19-9

  • Overall Survival at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    the estimated probability for the percentage of participants with overall survival at 12 months.

  • Liver Transplant Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The number of patients receiving liver transplant among patients who initially have tumors ≤3 cm

  • Freedom From Local Progression at 12 Months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    the proportion of patients who experienced a local recurrence at 12 months with death as a competing risk

  • Liver Transplant Conversion Rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The ability to successfully perform liver transplant among patients who initially have tumor >3 cm

  • Median Time to Overall Survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    The time to overall survival is defined as the time to death from any cause. The median was determined via Kaplan Meier methodology.


Enrollment: 2
Study Start Date: January 2011
Study Completion Date: July 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: External photon radiation
Drug: Gemcitabine
100 mg/m2, IV
Other Name: 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 Name: Xeloda
Drug: 5FU
200 mg/m2
Other Names:
  • Fluorouracil
  • Adrucil
  • Carac
  • Efudix
  • Efudex
  • Fluoroplex
Procedure: Liver transplantation

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 &#8805; 500 x 109/L (&#8805; 1500/mm3), Platelets &#8805; 5 x 109/L (&#8805; 50,000/mm3), Hgb &#8805; 9g/dL
    • Adequate liver function: Total bilirubin &#8804;1.5 x upper limit of normal (ULN); ALT and/or AST & alkaline phosphatase &#8804; 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 &#8805; 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 &#8804; 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01151761

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Daniel T Chang Stanford University
  More Information

Responsible Party: Daniel T. Chang, Assistant Professor, Stanford University
ClinicalTrials.gov Identifier: NCT01151761     History of Changes
Other Study ID Numbers: HEP0032  HEP0032 
Study First Received: June 15, 2010
Results First Received: July 3, 2013
Last Updated: June 30, 2016
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Liver Neoplasms
Cholangiocarcinoma
Bile Duct Neoplasms
Gallbladder Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Biliary Tract Neoplasms
Bile Duct Diseases
Biliary Tract Diseases
Gallbladder Diseases
Gemcitabine
Cisplatin
Carboplatin
Capecitabine
Liver Extracts
Antineoplastic Agents
Hematinics
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2016