Title: ABC-07: Addition of stereotactic body radiotherapy to systemic chemotherapy in locally advanced biliary tract cancers
Funder: Cancer Research UK

Abstract: Background Biliary tract cancers (BTC) are uncommon cancers comprising cholangiocarcinoma (intrahepatic, hilar and extrahepatic), gallbladder and ampullary cancers. The current standard-of-care (developed through this group) for patients with advanced disease is combination chemotherapy Cisplatin and Gemcitabine (CisGem). The optimal strategy for patients with locally advanced / unresectable disease has not been determined and this patient subgroup may be candidates for the evaluation of a locally-targeted approach, such as external beam radiotherapy. Stereotactic radiotherapy is a novel method of delivering focused radiotherapy over a short time (1-2 weeks vs 5-6 weeks) in higher biological doses (80-100Gy vs 45-50Gy) than standard fractionated radiotherapy, with minimal side effects due to the small volumes of normal tissues which are irradiated. We propose that high dose hypo-fractionated radiotherapy using stereotactic body radiotherapy (SBRT) could be integrated into the treatment paradigm for locally advanced, non-metastatic, BTC. Aims The overall aim is to evaluate the efficacy of 6 cycles of CisGem chemotherapy followed by stereotactic ablative radiotherapy (SBRT) compared to 8 cycles of CisGem. Primary endpoint: To evaluate the relative merits of adding SBRT to CisGem chemotherapy in terms of progression free survival. Methods 83 patients with locally advanced inoperable cholangiocarcinoma, which will include the patients recruited in the feasibility stage. All patients are registered in the trial and receive 6 cycles of CisGem. Those who have SD or PR after cycle 4 are then randomised in a 2:1 ration to either SBRT or a further 2 cycles of chemotherapy. Patients will be followed up 3- monthly until disease progression or for up to two years after registration. Following progression patients will be followed up as per standard practice and survival data will becollected. The decision as to whether the experimental arm should be taken forward is based on comparing observed/target PFS from 45% to 62% at 12 months. This is equivalent to an extension of the median PFS from 10.4 to 17.4 months or a target HR 0.60. How the results of this research will be used. If the objectives of the trial are met radiotherapy could be considered for incorporation in the standard of care or integrated in other research that involves the use of immune therapy.

Lay abstract: Background Biliary tract cancers (BTC) are uncommon cancers comprising cholangiocarcinoma (intrahepatic, hilar and extrahepatic), gallbladder and ampullary cancers. The current standard-of-care (developed through this group) for patients with advanced disease is combination chemotherapy Cisplatin and Gemcitabine (CisGem). The optimal strategy for patients with locally advanced / unresectable disease has not been determined and this patient subgroup may be candidates for the evaluation of a locally-targeted approach, such as external beam radiotherapy. Stereotactic radiotherapy is a novel method of delivering focused radiotherapy over a short time (1-2 weeks vs 5-6 weeks) in higher biological doses (80-100Gy vs 45-50Gy) than standard fractionated radiotherapy, with minimal side effects due to the small volumes of normal tissues which are irradiated. We propose that high dose hypo-fractionated radiotherapy using stereotactic body radiotherapy (SBRT) could be integrated into the treatment paradigm for locally advanced, non-metastatic, BTC. Aims The overall aim is to evaluate the efficacy of 6 cycles of CisGem chemotherapy followed by stereotactic ablative radiotherapy (SBRT) compared to 8 cycles of CisGem. Primary endpoint: To evaluate the relative merits of adding SBRT to CisGem chemotherapy in terms of progression free survival. Methods 83 patients with locally advanced inoperable cholangiocarcinoma, which will include the patients recruited in the feasibility stage. All patients are registered in the trial and receive 6 cycles of CisGem. Those who have SD or PR after cycle 4 are then randomised in a 2:1 ration to either SBRT or a further 2 cycles of chemotherapy. Patients will be followed up 3- monthly until disease progression or for up to two years after registration. Following progression patients will be followed up as per standard practice and survival data will becollected. The decision as to whether the experimental arm should be taken forward is based on comparing observed/target PFS from 45% to 62% at 12 months. This is equivalent to an extension of the median PFS from 10.4 to 17.4 months or a target HR 0.60. How the results of this research will be used. If the objectives of the trial are met radiotherapy could be considered for incorporation in the standard of care or integrated in other research that involves the use of immune therapy.

Research activity codes: 6.1 PHARMACEUTICALS;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS