Clinical trial NCT01151761: Phase II SBRT & Chemo for Unresectable Cholangiocarcinoma Followed by Liver Transplantation
Official title: Phase II Study of Stereotactic Body Radiotherapy (SBRT) and Chemotherapy for Unresectable Cholangiocarcinoma Followed by Liver Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cholangiocarcinoma
Hepatobiliary Neoplasm
Liver Cancer
Bile Duct Cancer
Cancer of Gallbladder
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2010-06-28
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of cholangiocarcinoma by any of the below:

  * Positive transcatheter biopsy or brush cytology
  * CA 19-9 \&#8805; 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.

Primary outcomes:
measure: Progression-free Survival at 12 Months
timeFrame: 12 months
Secondary outcomes:
measure: Pathologic Complete Response Rate
timeFrame: 12 months
measure: Serum CA 19-9 Levels
timeFrame: 12 months
measure: Overall Survival at 12 Months
timeFrame: 12 months
measure: Liver Transplant Rate
timeFrame: 12 months
measure: Freedom From Local Progression at 12 Months
timeFrame: 12 months
measure: Liver Transplant Conversion Rate
timeFrame: 12 months
measure: Median Time to Overall Survival
timeFrame: 18 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Daniel T Chang
role: PRINCIPAL_INVESTIGATOR
References: