Stereotactic Body Radiation Therapy for Unresectable Perihilar Cholangiocarcinoma

Not Applicable

Completed

• Conditions: Klatskin Tumor
• Interventions: Radiation: Stereotactic body radiation therapy

• Registration Number: NCT03307538
• Lead Sponsor: Erasmus Medical Center

Brief Summary

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. However, small and most often retrospective studies combining chemotherapy with SBRT showed promising results with overall survival reaching up to 33-35 months.

Based upon these observations, the investigators designed a local feasibility trial with SBRT after chemotherapy in patients with unresectable perihilar cholangiocarcinoma in order to try to confirm the observed tolerability of adding SBRT to standard chemotherapy. The expected time to include the required patients for this pilot study will be one year.

Objective:

To assess feasibility of SBRT as add on treatment after standard chemotherapy.

Study design:

Local feasibility trial.

Study population:

Patients diagnosed with perihilar cholangiocarcinoma, 18 years of age or older, T1-4 N0-1 M0 (AJCC 7th Edition), after completion of standard chemotherapy. Exclusion criteria are local tumor growth into either stomach, colon, duodenum, pancreas or abdominal wall. Sample size will be 6 patients.

Intervention:

SBRT will be delivered in 15 fractions of 3 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 feasibility measured by radiotherapy induced toxicity according to CTC v4.0.3.

Secondary endpoints will be:

* Quality of life

* Local progression

* Progression free survival

* Overall survival

* Cellular radiosensitivity.

Detailed Description

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 distant metastases. For these patients 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 supports the routine use of stereotactic body radiation therapy (SBRT) for unresectable cholangiocarcinoma. However, small and most often retrospective studies combining chemotherapy with SBRT showed promising results with overall survival reaching up to 33-35 months.

This pilot study is designed as a first step to confirm and extend these findings. Up to six patients diagnosed with unresectable perihilar cholangiocarcinoma will be treated with standard chemotherapy followed by SBRT in order to assess possible severe side effects of the treatment. As part of this research, patients will be followed with CT- or MRI-scan and blood tests exams until progression. In addition to this clinical evaluation, the investigators will also work towards developing a predictive assay for radiotherapy response of both normal and tumor tissue by establishing normal tissue and tumor organoids and determining several key parameters for their response to ionizing radiation treatment.

Study Timeline

• Study First Submitted: 2017-09-26
• Study First Submitted QC: 2017-10-05
• Study First Posted: 2017-10-11
• Study Start: 2017-11-06
• Primary Completion: 2020-03-30
• Study Completion: 2020-06-30
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-25
• Last Update Posted: 2021-01-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Stereotactic body radiation therapy	Stereotactic body radiation therapy	-

Primary Outcome Measures

Name	Time	Method
Acute toxicity	3 months	Limiting toxicity will be defined as more than one patient with grade 4 hepatobiliary toxicity related to study procedures, or more than one patient with grade 3 gastrointestinal toxicity related to study procedures, occurring in the period up to 3 months after the last SBRT administration.

Secondary Outcome Measures

Name	Time	Method
Overall survival	2 years
Quality of life	2 years	Assessed by means of the EuroQoL-5D questionnaire
Local progression	2 years	Measured on MRI
Progression free survival	2 years	Time from treatment to progression measured on CT
Cellular radiosensitivity	2 years	A predictive assay will be developed for radiotherapy response of both normal and tumor tissue by establishing normal tissue and tumor organoids and determining several key parameters for their response to ionizing radiation treatment.

Trial Locations

Locations (1)

Erasmus MC; 🇳🇱 Rotterdam, Zuid Holland, Netherlands