Stereotactic Body Radiation Therapy After Chemotherapy for Unresectable Perihilar Cholangiocarcinoma

NCT ID: NCT06493734

Last Updated: 2025-07-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-07-01

Study Completion Date

2028-03-01

Brief Summary

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The objective of this study is to evaluate the efficacy of stereotactic body radiation therapy (SBRT) as additional treatment after standard chemotherapy regarding tumor local control, toxicity, progression-free survival (PFS), overall survival and quality of life. In addition, the objective is to explore the value of immunodynamics in peripheral blood for predicting PFS in patients undergoing chemotherapy.

Detailed Description

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Rationale:

For patients with perihilar cholangiocarcinoma, surgery is the only treatment modality that can result in cure. Unfortunately, in the majority of these patients the tumors are found to be unresectable at presentation due to local invasive tumor growth or the presence of distal metastases. For patients with unresectable cholangiocarcinoma, palliative chemotherapy is the standard treatment, yielding an estimated median overall survival of 12-15.2 months.

There is no evidence from randomized trials that support the routine use of stereotactic body radiation therapy (SBRT) for cholangiocarcinoma. The STRONG phase I feasibility study showed favorable outcomes regarding safety, and the therapy was generally well tolerated. Based upon these observations, a phase II multi-center study with SBRT after chemotherapy in patients with unresectable perihilar cholangiocarcinoma is proposed, in order to further research the efficacy of adding SBRT to standard chemotherapy.

In addition, an explorative translational research component is part of the study, in which peripheral immunodynamics, specifically myeloid nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB) signaling and interferon-stimulated genes (ISG) responses within the myeloid cells, may help to predict survival after chemotherapy and may also help to predict the value of additional treatment with radiotherapy.

Objective:

The objective of this study is to evaluate the efficacy of SBRT as additional treatment after standard chemotherapy regarding tumor local control, toxicity, progression-free survival (PFS), overall survival and quality of life. In addition, to explore the value of immunodynamics in peripheral blood for predicting PFS in patients undergoing chemotherapy.

Study design:

Single-arm, multicenter phase II study.

Study population:

The initial translational part of the study will be performed in patients diagnosed with unresectable perihilar cholangiocarcinoma, 18 years of age or older, T1-4 N0-2 M0 (AJCC staging 8th edition), eligible for gemcitabine-based chemotherapy. Exclusion criteria are tumor extension into either stomach, colon, duodenum, pancreas or abdominal wall. After completion of chemotherapy and no local or distant progression during or after chemotherapy, the patients will proceed to SBRT if they are still eligible based on the inclusion and exclusion criteria. It may occur that patients do not give consent for the translational part of the study, but they may wish to participate in the SBRT part of the trial and vice versa. Sample size will be 30 patients.

Intervention:

SBRT will be delivered in 15 fractions of 4 to 4.5Gy after 8 cycles of chemotherapy. In case of toxicity causing premature termination of systemic treatment, the patient can still proceed to SBRT.

Main study parameters/endpoints:

The primary endpoint of this study is local tumour control, defined as time from inclusion to local radiological progression. Definition of progression is based on response evaluation criteria in solid tumours (RECIST) 1.1.

Secondary endpoints:

* Toxicity according to the Common Toxicity Criteria for Adverse Events (CTCAE) V.5.0 grading system.
* Biliary stent-related events (SRE).
* Progression-free survival defined as time from inclusion until radiological progression. Definition of progression is based on RECIST 1.1.
* Overall survival defined as time from inclusion until death from any cause.
* Quality of life (QoL), assessed by means of the EuroQol (EQ)-5D-5L (measure of health outcome in general population), and the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (QoL specific for patients with cancer) with the supplementary module EORTC QLQ-BIL21 (specific for CCA and gallbladder cancer).

Conditions

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Klatskin Tumor

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Stereotactic body radiation therapy

Single-arm study

Group Type EXPERIMENTAL

Stereotactic body radiation therapy

Intervention Type RADIATION

SBRT will be delivered in 15 fractions of 4 to 4.5Gy (risk-adapted), one fraction each weekday for 3 weeks.

Interventions

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Stereotactic body radiation therapy

SBRT will be delivered in 15 fractions of 4 to 4.5Gy (risk-adapted), one fraction each weekday for 3 weeks.

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

In order to be eligible to participate in the translational part of the study, a subject must be discussed in a liver tumor board, should be eligible for gemcitabine-based chemotherapy (and immunotherapy, if applicable), and should meet all of the following criteria pre-chemotherapy:

* Perihilar cholangiocarcinoma (pCCA) according to the criteria of the Mayo Clinic, Rochester: a positive or strongly suspicious intraluminal brush cytology or biopsy, or a radiographic malignant appearing stricture plus either: CA 19-9\>100 U/ml in the absence of acute bacterial cholangitis, or polysomy on fluorescence in situ hybridization (FISH), or a well-defined mass on cross sectional imaging
* One tumor mass
* Unresectable tumor or patient deemed unfit for surgery
* T1-T4 (AJCC staging 8th edition), N0-N2-M0 (AJCC staging 8th edition), radiologically or pathologically suspect. N1 is defined as one to three affected lymph nodes typically involving the hilar, cystic duct, common bile duct, hepatic artery, posterior pancreatoduodenal, and portal vein lymph nodes. N2 is defined as four or more affected lymph nodes from the sites described for N1. Endoscopic ultrasound (EUS) is leading in identifying pathological lymph nodes compared to CT.
* In case of (underlying) liver cirrhosis: Child-Pugh A
* Age ≥ 18 years
* ECOG performance status 0-1
* Written informed consent for the translational part of the study


In addition to the criteria mentioned above, patients should meet the following criteria to be eligible for the treatment with SBRT:

* Measurable disease to be selected as a target on a computed tomography (CT) or magnetic resonance imaging (MRI) scan, according to RECIST 1.1 criteria
* Finished gemcitabine-based chemotherapy treatment, preferably 8 cycles. If less cycles are given, patients are still eligible for this study
* Bilirubin ≤3.0 times normal value, aspartate aminotransferase (AST)/alanine transaminase (ALT) ≤5 times ULN
* Platelets ≥ 50x10E9/ l, Leukocytes \> 1.5x10E9/l, Hemoglobin (Hb) \> 6 mmol/l
* Willing and able to comply to the follow-up schedule
* Able to start SBRT within 12 weeks after completion of chemotherapy and immuno-therapy (if applicable)
* Written informed consent for the SBRT part of the study

Exclusion Criteria

* Prior surgery or transplantation of the liver
* Tumor extension in stomach, colon, duodenum, pancreas or abdominal wall
* Ascites
* Prior radiotherapy to the liver
* Current pregnancy

Progression (local or distant) during or after chemotherapy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dutch Cancer Society

OTHER

Sponsor Role collaborator

Erasmus Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Alejandra Mendez Romero

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alejandra Méndez Romero, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Locations

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Antwerp University Hospital / Sint-Augustinus Gasthuiszusters

Wilrijk, Antwerp, Belgium

Site Status NOT_YET_RECRUITING

University Hospital Brussels / Jules Bordet Institute

Brussels, Brussels Capital, Belgium

Site Status NOT_YET_RECRUITING

Radboud University Medical Center

Nijmegen, Gelderland, Netherlands

Site Status RECRUITING

Maastricht University Medical Center+ / Maastro Clinic Maastricht

Maastricht, Limburg, Netherlands

Site Status RECRUITING

Amsterdam University Medical Center

Amsterdam, North Holland, Netherlands

Site Status RECRUITING

University Medical Center Groningen

Groningen, Provincie Groningen, Netherlands

Site Status RECRUITING

Erasmus MC

Rotterdam, South Holland, Netherlands

Site Status RECRUITING

University Medical Center Utrecht

Utrecht, Utrecht, Netherlands

Site Status RECRUITING

Countries

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Belgium Netherlands

Central Contacts

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Alejandra Méndez Romero, MD, PhD

Role: CONTACT

+31 (0)10 7035792

Suus van Loosbroek, MSc

Role: CONTACT

Facility Contacts

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Prof. Ines Joye, MD, PhD

Role: primary

Christelle Bouchart, MD, PhD

Role: primary

Harm Westdorp, MD, PhD

Role: primary

Jeroen Buijsen, MD, PhD

Role: primary

Eva Versteijne, MD, PhD

Role: primary

Derk Jan de Groot, MD, PhD

Role: primary

Alejandra Méndez Romero, MD, PhD

Role: primary

+31 (0)10 7035792

Prof. Martijn Intven, MD, PhD

Role: primary

References

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van Loosbroek SY, Milder MTW, de Ruysscher D, Vaes RDW, den Toom W, Willemssen F, Eskens F, Homs MYV, Groot Koerkamp B, van Driel LMJW, Seppenwoolde Y, van Werkhoven E, Intven M, Haj Mohammad N, de Bruijne J, Versteijne E, Bruynzeel AM, Brandts F, Erdmann JI, Westdorp H, Braam PM, Tjwa ETTL, Bouchart C, Demols A, Gulyban A, Buijsen J, de Vos-Geelen J, Dewulf M, Joye I, Vandamme T, Vonghia L, de Groot DJ, Dieters M, Ubbels FJF, Hoogwater FJH, Heijmen B, Mendez Romero A. STRONG II trial: stereotactic body radiation therapy following chemotherapy for unresectable perihilar cholangiocarcinoma - a single-arm multicentre phase II study. BMJ Open. 2025 Jul 16;15(7):e097545. doi: 10.1136/bmjopen-2024-097545.

Reference Type DERIVED
PMID: 40669914 (View on PubMed)

Other Identifiers

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NL86210.078.24

Identifier Type: -

Identifier Source: org_study_id

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