Stereotactic Body Radiation Therapy After Chemotherapy for Unresectable Perihilar Cholangiocarcinoma
- Conditions
- Klatskin Tumor
- Interventions
- Radiation: Stereotactic body radiation therapy
- Registration Number
- NCT06493734
- Lead Sponsor
- Erasmus Medical Center
- Brief Summary
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
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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Stereotactic body radiation therapy Stereotactic body radiation therapy Single-arm study
- Primary Outcome Measures
Name Time Method Local tumor control 42 months (maximum follow-up time) Local tumor control is defined as time from inclusion to local radiological progression. Definition of progression is based on response evaluation criteria in solid tumors (RECIST) 1.1. In RECIST 1.1, response of a tumor to treatment is defined as either complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD).
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) 42 months (maximum follow-up time) PFS is defined as time from inclusion until radiological progression. Definition of progression is based on RECIST 1.1.
Overall survival (OS) 42 months (maximum follow-up time) OS is defined as time from inclusion until death from any cause.
Adverse events 42 months (maximum follow-up time) Adverse events assessed by the Common Toxicity Criteria for Adverse Events (CTCAE) V.5.0
Biliary stent-related events (SRE) 42 months (maximum follow-up time) The definition of SRE in this study is based on the definition used in the study by Lamarca et al. (https://doi.org/10.3748/wjg.v22.i26.6065). A SRE is defined as any one or more of the following: 1. any episode of jaundice which is considered significant enough for new stenting or medical treatment and is confirmed by radiological imaging to be associated with biliary dilatation; 2. any episode of infection which is clinically in keeping with cholangitis (bile duct infection) requiring antibiotic therapy; 3. bacteraemia with isolation in blood cultures of bacteria suspected to have originated in the biliary tract; and 4. any episode of cholecystitis or gallbladder perforation.
Quality of life (QoL) - EQ-5D-5L 36 months Assessed by means of the EuroQol (EQ)-5D-5L (measure of health outcome in general population).
Quality of life (QoL) - QLQ-C30 36 months Assessed by means of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (QoL specific for patients with cancer).
Quality of life (QoL) - QLQ-BIL21 36 months Assessed by means of the supplementary module EORTC QLQ-BIL21 (specific for CCA and gallbladder cancer).
Trial Locations
- Locations (8)
Antwerp University Hospital / Sint-Augustinus Gasthuiszusters
🇧🇪Wilrijk, Antwerp, Belgium
University Hospital Brussels / Jules Bordet Institute
🇧🇪Brussels, Brussels-capital, Belgium
Radboud University Medical Center
🇳🇱Nijmegen, Gelderland, Netherlands
Maastricht University Medical Center+ / Maastro Clinic Maastricht
🇳🇱Maastricht, Limburg, Netherlands
Amsterdam University Medical Center
🇳🇱Amsterdam, Noord-Holland, Netherlands
Erasmus MC
🇳🇱Rotterdam, Zuid-Holland, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
University Medical Center Utrecht
🇳🇱Utrecht, Netherlands