Clinical trial · Interventional

Evaluation of Combined Modality Protons and Hepatic Transplantation for Hilar Cholangiocarcinoma

Evaluation of Combined Modality Protons and Hepatic Transplantation for Hilar Cholangiocarcinoma (an Evaluative Commissioning in Protons Study)

NCT06434493CI-TRIAL-00080011EMPHATICnot yet recruitingN/AClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

Proton Beam Therapy (PBT) is an advanced radiotherapy technique. There are two National Health Service (NHS) PBT treatment centres in the United Kingdom (UK), in Manchester and London. The NHS is committed to ensuring the best use of this limited resource by investigating which patients will benefit from PBT. Evaluative Commissioning in Protons (ECIP) is a programme of studies exploring the role of PBT in different types of cancer. The studies are funded by NHS England. ECIP studies are not randomised studies, which means that all eligible patients will be offered PBT. Any eligible patient in the UK can be referred, and accommodation is available for patients who don't live close to a PBT centre. The main benefit of PBT, compared with standard photon radiotherapy, is the predicted reduction in radiation dose to surrounding healthy tissues. With photon radiotherapy, some radiation passes beyond the target area, affecting healthy tissues and causing side-effects. With PBT, the radiation dose stops within the target area, causing less damage to surrounding tissues, and limiting side effects. EMPHATIC is a study within the ECIP programme. In EMPHATIC, the investigators are looking to see whether a combination of treatments, including PBT, chemotherapy and a liver transplant, can be used to treat patients with cholangiocarcinoma (bile duct cancer). EMPHATIC offers patients whose cancer can't be removed with surgery (unresectable) a potentially curative treatment option. There is evidence that liver transplant is a curative treatment option in patients with cholangiocarcinoma. There is a risk that the cancer may grow or spread whilst waiting for a transplant, potentially making patients ineligible. PBT and chemotherapy is thought to be the best way to control the cancer, until a liver transplant can be performed. EMPHATIC will look at how a combination of PBT and chemotherapy, followed by a liver transplant, can be used to curatively treat patients with unresectable cholangiocarcinomas.

Conditions

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Cholangiocarcinoma	Cholangiocarcinoma	ONTOLOGY_EXACT	0.98

Interventions

Interventions (4)

Intervention	Type	Mapped drug	Match
Cisplatin & Gemcitabine intravenous chemotherapy	Drug	—	UNRESOLVED
Concurrent oral capecitabine chemotherapy	Drug	—	UNRESOLVED
Orthotropic Liver Transplant	Procedure	—	UNRESOLVED
Proton Beam Therapy	Radiation	—	UNRESOLVED

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
Proton Beam Therapy
description
All patients to be offered neoadjuvant proton beam therapy to a dose of 45 Gray (Gy) in 15 fractions over 3 weeks, with a tumour boost to 67.5 Gray (Gy), and alongside concurrent oral capecitabine 625mg/m2 twice daily on radiation days.
interventionNames
1. Radiation: Proton Beam Therapy
2. Drug: Concurrent oral capecitabine chemotherapy
3. Drug: Cisplatin & Gemcitabine intravenous chemotherapy
4. Procedure: Orthotropic Liver Transplant

Primary outcomes (2)

measure
Incidence of Common Toxicity Criteria for recording Adverse Events (CTCAE) Grade 3 and above toxicity
timeFrame
Up to 90 days post neoadjuvant chemo-radiation.
description
Incidence of Grade ≥ 3 toxicity using CTCAE (grades 0-5) up to 90 days following completion of neoadjuvant (chemo)-PBT and liver transplant. Higher score indicates worse outcome.

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 17 Years

Show eligibility criteria text

Inclusion Criteria:

General criteria

* Age 17 years and over
* Performance status 0 or 1 (Eastern Cooperative Oncology Group)
* Suitable for liver transplantation as determined by Multi Disciplinary Team (MDT)
* Able to tolerate neoadjuvant therapy.
* A history of primary sclerosing cholangitis (PSC) will be a necessary eligibility criterion at the start of the study. Part-way through recruitment to the study, the eligibility criteria may be broadened, allowing patients with sporadic / non-PSC unresectable cholangiocarcinoma to also be considered. The decision to do this will be taken by the Study Management Group, who will be monitor results closely, following an interim analysis after the first 10 patients. Suitability for Orthotropic Liver Transplant will continue to be confirmed in the regional Hepato Biliary cancer MDT.

Specific criteria

* Presence of a dominant hilar stricture or mass \<3cm on cross-sectional imaging
* Histologically proven cholangiocarcinoma by brush cytology or biopsy via Endoscopic Retrograde Cholangiopancreatography (ERCP) or Percutaneous Transhepatic Cholangiography (PTC)
* No metastatic disease, including to regional lymph nodes.

Exclusion Criteria:

General criteria

* Inability to consent
* Poor performance status
* Failed fitness assessment
* Extrahepatic disease at any stage of presentation, assessment and treatment
* Prior biliary resection or hilar dissection for attempted resection within the past 12 months
* Prior malignancy in the last 5 years (excluding early breast, prostate, cervix and non melanoma skin cancers)

Specific criteria

* Estimated Glomerular Filtration Rate (eGFR) \<30
* Prior radiation to the upper abdomen
* Uncontrolled infection
* Duodenal invasion

References

Publications (3)

BACKGROUNDDe Vreede I, Steers JL, Burch PA, Rosen CB, Gunderson LL, Haddock MG, Burgart L, Gores GJ. Prolonged disease-free survival after orthotopic liver transplantation plus adjuvant chemoirradiation for cholangiocarcinoma. Liver Transpl. 2000 May;6(3):309-16. doi: 10.1053/lv.2000.6143. PMID 10827231
BACKGROUNDSudan D, DeRoover A, Chinnakotla S, Fox I, Shaw B Jr, McCashland T, Sorrell M, Tempero M, Langnas A. Radiochemotherapy and transplantation allow long-term survival for nonresectable hilar cholangiocarcinoma. Am J Transplant. 2002 Sep;2(8):774-9. doi: 10.1034/j.1600-6143.2002.20812.x. PMID 12243499
BACKGROUNDCambridge WA, Fairfield C, Powell JJ, Harrison EM, Soreide K, Wigmore SJ, Guest RV. Meta-analysis and Meta-regression of Survival After Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma. Ann Surg. 2021 Feb 1;273(2):240-250. doi: 10.1097/SLA.0000000000003801. PMID 32097164