Cholangiocarcinoma
Conditions
Brief summary
The study evaluates impact of high dose radiation on overall survival in patients with unresectable nonmetastatic cholangiocarcinoma. The study randomizes patient between systemic chemotherapy alone and systemic chemotherapy and high dose radiation
Detailed description
Currently the standard of care of unresectable non-metastatic cholangiocarcinoma is chemotherapy which has a median survival of 11.7 months (ABC-02 study). While this study included almost 60% of patients with cholangiocarcinomas (intrahepatic, extra hepatic and hilar), almost 73-76% of patients in each arm had metastases to begin with. And while the overall survival of the entire cohort was significantly improved by gemcitabine plus cisplatin compared to cisplatin alone, the hazard ratios for intrahepatic {0.57 (0.34-0.94)}, extra hepatic {0.73 (0.43-1.23)} and hilar cholangiocarcinomas {0.59 (0.32-1.09)} were all insignificant. Even though concurrent chemoradiation+/= brachytherapy has been used for management of cholangiocarcinomas for more than 3 decades the lack of level I evidence prevents from it being recommended as the first line management across multidisciplinary clinics. While either modality alone rarely yields survival of more than 12 months, recent reports of improved median survival with combination of high dose radiation and systemic chemotherapy necessitates investigation into role of combination of high dose (chemo) radiation and systemic chemotherapy. All patients with diagnosis of nonmetastatic unresectable cholangiocarcinoma who fulfill the study eligibility criteria will be evaluated for study participation. Patients will undergo upfront randomization into one of the study arms (systemic chemotherapy alone vs Systemic chemotherapy+ High dose radiation) The study stratification criteria will be done according the primary site i.e. Intrahepatic vs Extrahepatic.
Interventions
RADIATIONHigh Dose Radiation
The aim will be to deliver 52.5-60 Gy/ 25 fractions to the gross disease and 45 Gy/ 25 fractions to suspected microscopic disease along with weekly gemcitabine (300 mg/ m2) .
DRUGSystemic chemotherapy
This arm will receive maximum 8 cycles of gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 delivered on day 1 and 8 every 3 weekly.
Sponsors
Tata Memorial Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>18 years * Performance Status 0-2 * Tissue diagnosis of adenocarcinoma of the biliary tract. Wherever tissue diagnosis is not feasible in spite of repeated attempts a multidisciplinary consensus on clinicoradiological diagnosis of cholangiocarcinoma (CA 19-9= 100mg/ml with a radiological evidence of malignant stricture) should be made and patients consent should be available for treatment without tissue diagnosis. * Unresectable disease as determined by hepatobiliary surgical team. * No evidence of peritoneal or distant metastasis. * No radiological evidence of paraaortic nodal disease. * Child A or Child B (score 7) * Ability to tolerate radical treatment.
Exclusion criteria
* Multicentric intrahepatic cholangiocarcinoma (however adjacent satellite lesions are permitted) * Inability to deliver safe radiation due to high tumor/ liver ratio. * Active cholangitis. * Expected Survival\<6 months. * Unresolved biliary tract obstruction. * Inability in deliver systemic chemotherapy (persistent bilirubin\>3)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 3 years from completion of study | The trial is designed to assess a 36 month benefit overall survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| loco-regional progression free survival | 3 years from completion of accrual | Will compare the loco-regional progression free survival between both the arms |
| Toxicity Assessment | upto 3 years | Assessment will be done according to CTCAE v4.0 |
| Quality of Life Assessment of patients over a period of time | 3 years from completion of accrual | Assessment will be done according to Fact-Hep(version 4) |
| Surgical Resectability Rates | 6 weeks from completion of primary treatment | To assess the number of patient who can be taken for surgery in view of good response after treatment |
| cause specific survival | 3 years from completion of accrual | Will compare the cause specific survival between both the arms |
Countries
India
Contacts
Primary ContactSupriya Chopra, MD
Backup ContactSupriya Chopra, MD
Outcome results
None listed