Cholangiocarcinoma, Hepatobiliary Neoplasm, Liver Cancer, Bile Duct Cancer, Cancer of Gallbladder
Conditions
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.
Interventions
PROCEDUREStereotactic Body Radiotherapy
Standard of care
DRUGGemcitabine
100 mg/m2, IV
DRUGCisplatin
25 mg/m2, IV
DRUGCarboplatin
AUC 2, based on Calvert formula, IV
DRUGCapecitabine
1000 mg/m2, PO
DRUG5FU
200 mg/m2
PROCEDURELiver transplantation
Sponsors
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival at 12 Months | 12 months | Progression free survival is defined to be the time to progression of disease or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum CA 19-9 Levels | 12 months | Initial level of Cancer antigen 19-9 |
| Overall Survival at 12 Months | 12 months | the estimated probability for the percentage of participants with overall survival at 12 months. |
| Liver Transplant Rate | 12 months | The number of patients receiving liver transplant among patients who initially have tumors ≤3 cm |
| Pathologic Complete Response Rate | 12 months | Pathologic complete response will be defined as no residual tumor cells seen on the explanted liver specimen. |
| Liver Transplant Conversion Rate | 12 months | The ability to successfully perform liver transplant among patients who initially have tumor \>3 cm |
| Median Time to Overall Survival | 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. |
| Freedom From Local Progression at 12 Months | 12 months | the proportion of patients who experienced a local recurrence at 12 months with death as a competing risk |
Countries
United States
Participant flow
Recruitment details
The location is the Stanford Cancer Center. The study was open to accrual 1/18/2011. The study closed on 9/28/2012.
Participants by arm
| Arm | Count |
|---|---|
| SBRT, Chemotherapy 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 | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | SBRT, Chemotherapy and Liver Transplantation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 64.5 years STANDARD_DEVIATION 9.19 |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 2 |
| serious Total, serious adverse events | 1 / 2 |
Outcome results
Primary
Progression-free Survival at 12 Months
Progression free survival is defined to be the time to progression of disease or death.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SBRT and Chemo | Progression-free Survival at 12 Months | 0 participants |
Comparison: The median Progression Free Survival (PFS) time as calculated using Kaplan Meier methodology. For PFS both death and progression are counted as events.95% CI: [7, 10]
Secondary
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
Time frame: 12 months
Population: Neither of the two patients that participated in the study had a local recurrence prior to dying.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SBRT and Chemo | Freedom From Local Progression at 12 Months | 0 percentage of patients |
Secondary
Liver Transplant Conversion Rate
The ability to successfully perform liver transplant among patients who initially have tumor \>3 cm
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SBRT and Chemo | Liver Transplant Conversion Rate | 0 participants |
Secondary
Liver Transplant Rate
The number of patients receiving liver transplant among patients who initially have tumors ≤3 cm
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SBRT and Chemo | Liver Transplant Rate | 0 participants |
Secondary
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.
Time frame: 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SBRT and Chemo | Median Time to Overall Survival | 8.5 months |
Secondary
Overall Survival at 12 Months
the estimated probability for the percentage of participants with overall survival at 12 months.
Time frame: 12 months
Population: There were only two patients analyzed. Please take that under advisement when looking at the results.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SBRT and Chemo | Overall Survival at 12 Months | 0 probability |
Secondary
Pathologic Complete Response Rate
Pathologic complete response will be defined as no residual tumor cells seen on the explanted liver specimen.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SBRT and Chemo | Pathologic Complete Response Rate | 0 participants |
Secondary
Serum CA 19-9 Levels
Initial level of Cancer antigen 19-9
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| SBRT and Chemo | Serum CA 19-9 Levels | 3329.1 U/ml |