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

Phase 2
Terminated
Conditions
Cholangiocarcinoma
Hepatobiliary Neoplasm
Liver Cancer
Bile Duct Cancer
Cancer of Gallbladder
Interventions
Procedure: Stereotactic Body Radiotherapy
Drug: Gemcitabine
Drug: Cisplatin
Drug: Carboplatin
Drug: Capecitabine
Drug: 5FU
Procedure: Liver transplantation
Registration Number
NCT01151761
Lead Sponsor
Stanford University
Brief Summary

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).

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
2
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

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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.

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
SBRT, Chemo and Liver TransplantationStereotactic Body RadiotherapyThe 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
SBRT, Chemo and Liver Transplantation5FUThe 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
SBRT, Chemo and Liver TransplantationLiver transplantationThe 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
SBRT, Chemo and Liver TransplantationCisplatinThe 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
SBRT, Chemo and Liver TransplantationGemcitabineThe 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
SBRT, Chemo and Liver TransplantationCarboplatinThe 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
SBRT, Chemo and Liver TransplantationCapecitabineThe 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
Primary Outcome Measures
NameTimeMethod
Progression-free Survival at 12 Months12 months

Progression free survival is defined to be the time to progression of disease or death.

Secondary Outcome Measures
NameTimeMethod
Pathologic Complete Response Rate12 months

Pathologic complete response will be defined as no residual tumor cells seen on the explanted liver specimen.

Serum CA 19-9 Levels12 months

Initial level of Cancer antigen 19-9

Overall Survival at 12 Months12 months

the estimated probability for the percentage of participants with overall survival at 12 months.

Liver Transplant Rate12 months

The number of patients receiving liver transplant among patients who initially have tumors ≤3 cm

Freedom From Local Progression at 12 Months12 months

the proportion of patients who experienced a local recurrence at 12 months with death as a competing risk

Liver Transplant Conversion Rate12 months

The ability to successfully perform liver transplant among patients who initially have tumor \>3 cm

Median Time to Overall Survival18 months

The time to overall survival is defined as the time to death from any cause. The median was determined via Kaplan Meier methodology.

Trial Locations

Locations (1)

Stanford University School of Medicine

🇺🇸

Stanford, California, United States

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