Evaluation of Combined Modality Protons and Hepatic Transplantation for Hilar Cholangiocarcinoma

NCT06434493 | Not Yet Recruiting

• 1 other identifier: CFTSp218 (02)
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Cholangiocarcinoma

Keywords

proton beam therapy; protons; evaluative commissioning; liver transplant

Outcome Measures

Primary Outcomes (2)

• Incidence of Common Toxicity Criteria for recording Adverse Events (CTCAE) Grade 3 and above toxicity

  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.

  Up to 90 days post neoadjuvant chemo-radiation.

• Proportion of patients who undergo a successful liver transplant

  The proportion of patients who, following neoadjuvant (chemo)-PBT, undergo a successful liver transplant (measured at 90 days post-transplant).

  90 days post transplant.

Secondary Outcomes (16)

• Number of patients completing planned radiotherapy

  Up to 1 year

• Incidence of severe treatment related side effects

  Up to 2 years

• 1 year post completion of neoadjuvant therapy cancer-related mortality

  At 1 year

• 1 year post transplant overall survival

  At 1 year

• 1 year post transplant graft survival

  At 1 year

Study Arms (1)

Proton Beam Therapy

EXPERIMENTAL

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.

Radiation: Proton Beam Therapy; Drug: Concurrent oral capecitabine chemotherapy; Drug: Cisplatin & Gemcitabine intravenous chemotherapy; Procedure: Orthotropic Liver Transplant

Interventions

Proton Beam Therapy RADIATION

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)

Proton Beam Therapy

Concurrent oral capecitabine chemotherapy DRUG

All patients to be offered concurrent oral capecitabine 625mg/m2 twice daily on radiation days

Proton Beam Therapy

Cisplatin & Gemcitabine intravenous chemotherapy DRUG

Following chemoradiotherapy (PBT + capecitabine), and whilst on the liver transplant waiting list, patients will be offered up to 6 cycles of standard chemotherapy with cisplatin and gemcitabine.

Proton Beam Therapy

Orthotropic Liver Transplant PROCEDURE

If still eligible after neoadjuvant treatment (PBT + capecitabine), patients will be added to the liver transplant waiting list.

Proton Beam Therapy

Eligibility Criteria

• Age: 17 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead
• University College London Hospitals: collaborator
• University College, London: collaborator
• Royal Free Hospital NHS Foundation Trust: collaborator

Related Publications (3)

• De 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 BACKGROUND

• Sudan 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 BACKGROUND

• Cambridge 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 BACKGROUND

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Proton Therapy; Cisplatin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Heavy Ion Radiotherapy; Radiotherapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Maria Hawkins

  University College, London

  PRINCIPAL INVESTIGATOR

• Douglas Thorburn

  The Royal Free NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Romelie Rieu

CONTACT

0044 1619187172; romelie.rieu@nhs.net

Sally Falk

CONTACT

0044 1619187172; sally.falk@nhs.net

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: May 30, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: August 21, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share