Using radiation therapy after chemotherapy for inoperable bile duct cancer

Stereotactic Body Radiation Therapy After Chemotherapy for Unresectable Perihilar Cholangiocarcinoma: A Multicenter Phase II Trial (The STRONG 2 Trial)

This study is testing if adding a special type of radiation therapy after chemotherapy can help people with inoperable bile duct cancer live longer and feel better.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Erasmus Medical Center (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 8 sites (Wilrijk, Antwerp and 7 other locations)
• Trial ID: NCT06493734 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of stereotactic body radiation therapy (SBRT) as an additional treatment following standard chemotherapy for patients with unresectable perihilar cholangiocarcinoma, also known as Klatskin tumors. The research aims to assess tumor control, toxicity, progression-free survival, overall survival, and quality of life. Additionally, it explores the potential of immunodynamics in predicting patient outcomes based on blood samples. The study is designed as a phase II multi-center trial to gather more evidence on the efficacy of SBRT in this patient population.

Who should consider this trial

Good fit: Ideal candidates include patients diagnosed with unresectable perihilar cholangiocarcinoma who are eligible for gemcitabine-based chemotherapy.

Not a fit: Patients with resectable tumors or those who do not qualify for chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve survival rates and quality of life for patients with unresectable perihilar cholangiocarcinoma.

How similar studies have performed: While there is limited evidence from randomized trials supporting the routine use of SBRT for cholangiocarcinoma, preliminary studies have shown favorable safety outcomes.

Eligibility criteria

Inclusion criteria translational part of the study:

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

Inclusion criteria SBRT 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 translational part of the study:

* 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
* Affected lymph nodes outside the regions described in the inclusion criteria

Exclusion criteria SBRT part of the study:

Progression (local or distant) during or after chemotherapy

Where this trial is running

Wilrijk, Antwerp and 7 other locations

• Antwerp University Hospital / Sint-Augustinus Gasthuiszusters — Wilrijk, Antwerp, Belgium (Not_yet_recruiting)
• University Hospital Brussels / Jules Bordet Institute — Brussels, Brussels Capital, Belgium (Not_yet_recruiting)
• Radboud University Medical Center — Nijmegen, Gelderland, Netherlands (Recruiting)
• Maastricht University Medical Center+ / Maastro Clinic Maastricht — Maastricht, Limburg, Netherlands (Recruiting)
• Amsterdam University Medical Center — Amsterdam, North Holland, Netherlands (Recruiting)
• University Medical Center Groningen — Groningen, Provincie Groningen, Netherlands (Recruiting)
• Erasmus MC — Rotterdam, South Holland, Netherlands (Recruiting)
• University Medical Center Utrecht — Utrecht, Utrecht, Netherlands (Recruiting)

Study contacts

• Principal investigator: Alejandra Méndez Romero, MD, PhD — Erasmus Medical Center
• Study coordinator: Alejandra Méndez Romero, MD, PhD

Conditions Klatskin Tumor; Klatskin tumor; Perihilar cholangiocarcinoma; Stereotactic body radiation therapy