Trial Title:
Stereotactic Body Radiation Therapy After Chemotherapy for Unresectable Perihilar Cholangiocarcinoma
NCT ID:
NCT06493734
Condition:
Klatskin Tumor
Conditions: Official terms:
Cholangiocarcinoma
Klatskin Tumor
Conditions: Keywords:
Klatskin tumor
Perihilar cholangiocarcinoma
Stereotactic body radiation therapy
Study type:
Interventional
Study phase:
N/A
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
Stereotactic body radiation therapy
Description:
SBRT will be delivered in 15 fractions of 4 to 4.5Gy (risk-adapted), one fraction each
weekday for 3 weeks.
Arm group label:
Stereotactic body radiation therapy
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-N1-M0 (AJCC
staging 8th edition), eligible for standard chemotherapy with cisplatin and gemcitabine.
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.
- 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).
Criteria for 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 standard 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-N1-M0 (AJCC staging 8th edition),
radiologically or pathologically suspect
- 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 chemotherapy treatment with gemcitabine and cisplatin, preferably 8 cycles.
If less cycles are given, patients are still eligible for this study
- Bilirubin ≤1.5 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
Exclusion criteria SBRT part of the study:
Progression (local or distant) during or after chemotherapy
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Antwerp University Hospital / Sint-Augustinus Gasthuiszusters
Address:
City:
Wilrijk
Zip:
2610
Country:
Belgium
Status:
Not yet recruiting
Contact:
Last name:
Prof. Ines Joye, MD, PhD
Email:
ines.joye@gza.be
Investigator:
Last name:
Prof. Ines Joye, MD, PhD
Email:
Principal Investigator
Facility:
Name:
University Hospital Brussels / Jules Bordet Institute
Address:
City:
Brussels
Zip:
1070
Country:
Belgium
Status:
Not yet recruiting
Contact:
Last name:
Christelle Bouchart, MD, PhD
Email:
Christelle.Bouchart@bordet.be
Investigator:
Last name:
Christelle Bouchart, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Radboud University Medical Center
Address:
City:
Nijmegen
Zip:
6525 GA
Country:
Netherlands
Status:
Not yet recruiting
Contact:
Last name:
Harm Westdorp, MD, PhD
Email:
harm.westdorp@radboudumc.nl
Investigator:
Last name:
Harm Westdorp, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Maastricht University Medical Center+ / Maastro Clinic Maastricht
Address:
City:
Maastricht
Zip:
6229 ET
Country:
Netherlands
Status:
Not yet recruiting
Contact:
Last name:
Jeroen Buijsen, MD, PhD
Email:
jeroen.buijsen@maastro.nl
Investigator:
Last name:
Jeroen Buijsen, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Amsterdam University Medical Center
Address:
City:
Amsterdam
Zip:
1081 HV
Country:
Netherlands
Status:
Not yet recruiting
Contact:
Last name:
Eva Versteijne, MD, PhD
Email:
e.versteijne@amsterdamumc.nl
Investigator:
Last name:
Eva Versteijne, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Erasmus MC
Address:
City:
Rotterdam
Zip:
3015 CD
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Alejandra Méndez Romero, MD, PhD
Phone:
+31 (0)10 7035792
Email:
a.mendezromero@erasmusmc.nl
Investigator:
Last name:
Alejandra Méndez Romero, MD, PhD
Email:
Principal Investigator
Facility:
Name:
University Medical Center Groningen
Address:
City:
Groningen
Zip:
9713 GZ
Country:
Netherlands
Status:
Not yet recruiting
Contact:
Last name:
Derk Jan de Groot, MD, PhD
Email:
d.j.a.de.groot@umcg.nl
Investigator:
Last name:
Derk Jan de Groot, MD, PhD
Email:
Principal Investigator
Facility:
Name:
University Medical Center Utrecht
Address:
City:
Utrecht
Zip:
3584 CX
Country:
Netherlands
Status:
Not yet recruiting
Contact:
Last name:
Prof. Frank Vleggaar, MD, PhD
Email:
f.vleggaar@umcutrecht.nl
Investigator:
Last name:
Prof. Frank Vleggaar, MD, PhD
Email:
Principal Investigator
Start date:
July 1, 2024
Completion date:
March 1, 2028
Lead sponsor:
Agency:
Erasmus Medical Center
Agency class:
Other
Collaborator:
Agency:
Dutch Cancer Society
Agency class:
Other
Source:
Erasmus Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06493734
