ClinicalTrials.gov
ClinicalTrials.gov Menu

Stereotactic Body Radiation Therapy for Unresectable Perihilar Cholangiocarcinoma (STRONG)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03307538
Recruitment Status : Recruiting
First Posted : October 11, 2017
Last Update Posted : December 8, 2017
Sponsor:
Information provided by (Responsible Party):
Alejandra Mendez Romero, 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.

Condition or disease Intervention/treatment Phase
Klatskin Tumor Radiation: Stereotactic body radiation therapy Not Applicable

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study to Determine the Feasibility of Stereotactic Body Radiation Therapy Following Chemotherapy for Unresectable Perihilar Cholangiocarcinoma. "The STRONG Trial"
Actual Study Start Date : November 6, 2017
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Stereotactic body radiation therapy Radiation: Stereotactic body radiation therapy
15 fractions of 3-4,5 Gy (risk-adapted)




Primary Outcome Measures :
  1. Acute toxicity [ Time Frame: 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 :
  1. Quality of life [ Time Frame: 2 years ]
    Assessed by means of the EORTC QLQ-C30 questionnaire

  2. Quality of life [ Time Frame: 2 years ]
    Assessed by means of the EORTC QLQ-BIL21 questionnaire

  3. Quality of life [ Time Frame: 2 years ]
    Assessed by means of the EuroQoL-5D questionnaire

  4. Local progression [ Time Frame: 2 years ]
    Measured on CT

  5. Local progression [ Time Frame: 2 years ]
    Measured on MRI

  6. Progression free survival [ Time Frame: 2 years ]
    Time from treatment to progression measured on CT

  7. Overall survival [ Time Frame: 2 years ]
  8. Cellular radiosensitivity [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03307538


Contacts
Contact: Alejandra Méndez Romero, MD, PhD +31 (0)10 7035829 a.mendezromero@erasmusmc.nl
Contact: Merel Koedijk, MD +31 (0)10 7041335 m.koedijk@erasmusmc.nl

Locations
Netherlands
Erasmus MC Recruiting
Rotterdam, Zuid Holland, Netherlands, 3015 CE
Contact: Alejandra Mendez Romero, MD PhD    +31 (0)10 7035829    a.mendezromero@erasmusmc.nl   
Principal Investigator: Alejandra Mendez Romero, MD, PhD         
Sponsors and Collaborators
Erasmus Medical Center
Investigators
Principal Investigator: Alejandra Méndez Romero, MD, PhD Erasmus Medical Center

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alejandra Mendez Romero, A. Méndez Romero MD, PhD, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT03307538     History of Changes
Other Study ID Numbers: NL 60588.078.17
First Posted: October 11, 2017    Key Record Dates
Last Update Posted: December 8, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alejandra Mendez Romero, Erasmus Medical Center:
Perihilar cholangiocarcinoma
Klatskin tumor
Stereotactic body radiation therapy

Additional relevant MeSH terms:
Cholangiocarcinoma
Klatskin Tumor
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms