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Stereotactic Body Radiation Therapy for Unresectable Perihilar Cholangiocarcinoma (STRONG)

Primary Purpose

Klatskin Tumor

Status

Completed

Phase

Not Applicable

Locations

Netherlands

Study Type

Interventional

Intervention

Stereotactic body radiation therapy

About this trial

This is an interventional treatment trial for Klatskin Tumor focused on measuring Perihilar cholangiocarcinoma, Klatskin tumor, Stereotactic body radiation therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

In order to be eligible to participate in this study, a subject must be discussed in a multidisciplinary liver tumor board and should meet all of the following criteria:

Patients diagnosed with perihilar cholangiocarcinoma according to the criteria of the Mayo Clinic, Rochester:
- Positive or strongly suspicious intraluminal brush 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 FISH, or
  - a well-defined mass on cross sectional imaging.
One tumor mass
Unresectable tumor
Finished chemotherapy treatment with Gemcitabine and Cisplatin, preferably 8 cycles. If less cycles are given, patients are still eligible for this study.
T1-T4 (AJCC staging 7th edition), before chemotherapy
N0-N1 (AJCC staging 7th edition), radiologically or pathologically suspect, before chemotherapy
Measurable disease to be selected as a target on CT/MRI-scan, according to RECIST criteria, after chemotherapy within 6 weeks prior to inclusion
Tumor visibility on CT
If liver cirrhosis is present, it should be well compensated, with Child-Pugh grade A.
Age ≥ 18 years
ECOG performance status 0-1
Bilirubin ≤1.5 times normal value, AST/ALT ≤5 times ULN, within 6 weeks prior to inclusion
Platelets ≥ 50x10E9/ l, Leukocytes > 1.5x10E9/l, Hb > 6 mmol/l, within 6 weeks prior to inclusion
Written informed consent, after chemotherapy
Willing and able to comply to the follow-up schedule
Able to start SBRT within 12 weeks after completion of chemotherapy.

Exclusion criteria:

Eligibility for resection
Prior surgery or transplantation
Multifocal tumor
Tumor extension in stomach, colon, duodenum, pancreas or abdominal wall.
N2, (AJCC staging 7th edition), radiologically or pathologically suspect, before chemotherapy
Distant metastases
Progression (local or distant) during or after chemotherapy Ascites
Previous radiotherapy to the liver
Current pregnancy

Sites / Locations

Erasmus MC

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Stereotactic body radiation therapy

Arm Description

Outcomes

Primary Outcome Measures

Acute toxicity

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

Quality of life

Assessed by means of the EORTC QLQ-C30 questionnaire

Quality of life

Assessed by means of the EORTC QLQ-BIL21 questionnaire

Quality of life

Assessed by means of the EuroQoL-5D questionnaire

Local progression

Measured on CT

Local progression

Measured on MRI

Progression free survival

Time from treatment to progression measured on CT

Overall survival

Cellular radiosensitivity

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.

Full Information

NCT ID

NCT03307538

First Posted

September 26, 2017

Last Updated

January 25, 2021

Sponsor

Erasmus Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT03307538

Brief Title

Stereotactic Body Radiation Therapy for Unresectable Perihilar Cholangiocarcinoma

Acronym

STRONG

Official Title

A Pilot Study to Determine the Feasibility of Stereotactic Body Radiation Therapy Following Chemotherapy for Unresectable Perihilar Cholangiocarcinoma. "The STRONG Trial"

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Completed

Study Start Date

November 6, 2017 (Actual)

Primary Completion Date

March 30, 2020 (Actual)

Study Completion Date

June 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Erasmus Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Klatskin Tumor

Keywords

Perihilar cholangiocarcinoma, Klatskin tumor, Stereotactic body radiation therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Stereotactic body radiation therapy

Arm Type

Experimental

Intervention Type

Radiation

Intervention Name(s)

Stereotactic body radiation therapy

Intervention Description

15 fractions of 3-4,5 Gy (risk-adapted)

Primary Outcome Measure Information:

Title

Acute toxicity

Description

Time Frame

3 months

Secondary Outcome Measure Information:

Title

Quality of life

Description

Assessed by means of the EORTC QLQ-C30 questionnaire

Time Frame

2 years

Title

Quality of life

Description

Assessed by means of the EORTC QLQ-BIL21 questionnaire

Time Frame

2 years

Title

Quality of life

Description

Assessed by means of the EuroQoL-5D questionnaire

Time Frame

2 years

Title

Local progression

Description

Measured on CT

Time Frame

2 years

Title

Local progression

Description

Measured on MRI

Time Frame

2 years

Title

Progression free survival

Description

Time from treatment to progression measured on CT

Time Frame

2 years

Title

Overall survival

Time Frame

2 years

Title

Cellular radiosensitivity

Description

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: In order to be eligible to participate in this study, a subject must be discussed in a multidisciplinary liver tumor board and should meet all of the following criteria: Patients diagnosed with perihilar cholangiocarcinoma according to the criteria of the Mayo Clinic, Rochester: Positive or strongly suspicious intraluminal brush 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 FISH, or a well-defined mass on cross sectional imaging. One tumor mass Unresectable tumor Finished chemotherapy treatment with Gemcitabine and Cisplatin, preferably 8 cycles. If less cycles are given, patients are still eligible for this study. T1-T4 (AJCC staging 7th edition), before chemotherapy N0-N1 (AJCC staging 7th edition), radiologically or pathologically suspect, before chemotherapy Measurable disease to be selected as a target on CT/MRI-scan, according to RECIST criteria, after chemotherapy within 6 weeks prior to inclusion Tumor visibility on CT If liver cirrhosis is present, it should be well compensated, with Child-Pugh grade A. Age ≥ 18 years ECOG performance status 0-1 Bilirubin ≤1.5 times normal value, AST/ALT ≤5 times ULN, within 6 weeks prior to inclusion Platelets ≥ 50x10E9/ l, Leukocytes > 1.5x10E9/l, Hb > 6 mmol/l, within 6 weeks prior to inclusion Written informed consent, after chemotherapy Willing and able to comply to the follow-up schedule Able to start SBRT within 12 weeks after completion of chemotherapy. Exclusion criteria: Eligibility for resection Prior surgery or transplantation Multifocal tumor Tumor extension in stomach, colon, duodenum, pancreas or abdominal wall. N2, (AJCC staging 7th edition), radiologically or pathologically suspect, before chemotherapy Distant metastases Progression (local or distant) during or after chemotherapy Ascites Previous radiotherapy to the liver Current pregnancy

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alejandra Méndez Romero, MD, PhD

Organizational Affiliation

Erasmus Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Erasmus MC

City

Rotterdam

State/Province

Zuid Holland

ZIP/Postal Code

3015 CE

Country

Netherlands

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34439146

Citation

Baak R, Willemssen FEJA, van Norden Y, Eskens FALM, Milder MTW, Heijmen BJM, Koerkamp BG, Sprengers D, van Driel LMJW, Klumpen HJ, den Toom W, Koedijk MS, IJzermans JNM, Mendez Romero A. Stereotactic Body Radiation Therapy after Chemotherapy for Unresectable Perihilar Cholangiocarcinoma: The STRONG Trial, a Phase I Safety and Feasibility Study. Cancers (Basel). 2021 Aug 7;13(16):3991. doi: 10.3390/cancers13163991.

Results Reference

derived

PubMed Identifier

30327398

Citation

Koedijk MS, Heijmen BJM, Groot Koerkamp B, Eskens FALM, Sprengers D, Poley JW, van Gent DC, van der Laan LJW, van der Holt B, Willemssen FEJA, Mendez Romero A. Protocol for the STRONG trial: stereotactic body radiation therapy following chemotherapy for unresectable perihilar cholangiocarcinoma, a phase I feasibility study. BMJ Open. 2018 Oct 15;8(10):e020731. doi: 10.1136/bmjopen-2017-020731.

Results Reference

derived

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Stereotactic Body Radiation Therapy for Unresectable Perihilar Cholangiocarcinoma

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