Clinical trial NCT02773485: Chemo Alone or in Combination With Radiation in Unresectable Cholangiocarcinoma
Official title: Phase III Randomized Trial of High Dose Chemoradiation and Systemic Chemotherapy vs Systemic Chemotherapy Alone in Patients With Unresectable Nonmetastatic Cholangiocarcinoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Cholangiocarcinoma
Lead sponsor: Tata Memorial Hospital
Sponsor class: OTHER_GOV
First posted: 2016-05-16
Enrollment: 155
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Overall Survival
timeFrame: 3 years from completion of study
Secondary outcomes:
measure: loco-regional progression free survival
timeFrame: 3 years from completion of accrual
measure: Toxicity Assessment
timeFrame: upto 3 years
measure: Quality of Life Assessment of patients over a period of time
timeFrame: 3 years from completion of accrual
measure: Surgical Resectability Rates
timeFrame: 6 weeks from completion of primary treatment
measure: cause specific survival
timeFrame: 3 years from completion of accrual
Other outcomes:
Locations:
city: Navi Mumbai
country: India
facility: Advanced Centre of Treatment Research and Education In Cancer,Tata Memorial Centre
state: Maharashtra
Study officials:
affiliation: ACTREC,Tata Memorial Centre
name: Supriya Chopra, MD
role: PRINCIPAL_INVESTIGATOR
References: