Chemo Alone or in Combination With Radiation in Unresectable Cholangiocarcinoma

Cholangiocarcinoma Clinical Trial

Official title:

Phase III Randomized Trial of High Dose Chemoradiation and Systemic Chemotherapy vs Systemic Chemotherapy Alone in Patients With Unresectable Nonmetastatic Cholangiocarcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02773485
• Other study ID #: TMC IRB 1457
• Status: Recruiting
• Phase: Phase 3
• Start date: May 2015
• Est. completion date: June 2025

Study information

• Verified date: October 2022
• Source: Tata Memorial Hospital
• Contact: Supriya Chopra, MD
• Phone: 09930958309
• Email: supriyasastri[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 155
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cholangiocarcinoma

Intervention

Radiation:
• High 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) .

Drug:
• Systemic 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.

Locations

Country	Name	City	State
India	Advanced Centre of Treatment Research and Education In Cancer,Tata Memorial Centre	Navi Mumbai	Maharashtra

Sponsors (1)

Lead Sponsor	Collaborator
Tata Memorial Hospital

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	The trial is designed to assess a 36 month benefit overall survival	3 years from completion of study
Secondary	loco-regional progression free survival	Will compare the loco-regional progression free survival between both the arms	3 years from completion of accrual
Secondary	Toxicity Assessment	Assessment will be done according to CTCAE v4.0	upto 3 years
Secondary	Quality of Life Assessment of patients over a period of time	Assessment will be done according to Fact-Hep(version 4)	3 years from completion of accrual
Secondary	Surgical Resectability Rates	To assess the number of patient who can be taken for surgery in view of good response after treatment	6 weeks from completion of primary treatment
Secondary	cause specific survival	Will compare the cause specific survival between both the arms	3 years from completion of accrual