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

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: Terminated
• Conditions: Cholangiocarcinoma; Bile Duct Cancer; Hepatobiliary Neoplasm; Liver Cancer; Cancer of Gallbladder
• Intervention / Treatment: Procedure: Stereotactic Body Radiotherapy; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin; Drug: Capecitabine; Drug: 5FU; 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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

Outcome Measure	Measure Description	Time Frame
Progression-free Survival at 12 Months	Progression free survival is defined to be the time to progression of disease or death.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response Rate	Pathologic complete response will be defined as no residual tumor cells seen on the explanted liver specimen.	12 months
Serum CA 19-9 Levels	Initial level of Cancer antigen 19-9	12 months
Overall Survival at 12 Months	the estimated probability for the percentage of participants with overall survival at 12 months.	12 months
Liver Transplant Rate	The number of patients receiving liver transplant among patients who initially have tumors ≤3 cm	12 months
Freedom From Local Progression at 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	The ability to successfully perform liver transplant among patients who initially have tumor >3 cm	12 months
Median Time to Overall Survival	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

• Sponsor: Stanford University

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: June 15, 2010
• First Submitted That Met QC Criteria: June 25, 2010
• First Posted (Estimate): June 28, 2010

Study Record Updates

• Last Update Posted (Estimate): July 29, 2016
• Last Update Submitted That Met QC Criteria: June 30, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Gallbladder Diseases; Biliary Tract Diseases; Bile Duct Diseases; Biliary Tract Neoplasms; Cholangiocarcinoma; Gallbladder Neoplasms; Bile Duct Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Carboplatin; Cisplatin; Fluorouracil; Capecitabine
• Other Study ID Numbers: HEP0032 (Other Identifier: Stanford University)