Stereotactic Body Radiation Therapy for Unresectable Perihilar Cholangiocarcinoma

Brief Title

Stereotactic Body Radiation Therapy for Unresectable Perihilar Cholangiocarcinoma

Official Title

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

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 Type

Interventional


Primary Outcome

Acute toxicity

Secondary Outcome

 Quality of life

Condition

Klatskin Tumor

Intervention

Stereotactic body radiation therapy

Study Arms / Comparison Groups

 Stereotactic body radiation therapy
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Radiation

Estimated Enrollment

6

Start Date

November 6, 2017

Completion Date

June 30, 2020

Primary Completion Date

March 30, 2020

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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Alejandra Méndez Romero, MD, PhD, , 

Location Countries

Netherlands

Location Countries

Netherlands

Administrative Informations


NCT ID

NCT03307538

Organization ID

NL 60588.078.17


Responsible Party

Principal Investigator

Study Sponsor

Erasmus Medical Center


Study Sponsor

Alejandra Méndez Romero, MD, PhD, Principal Investigator, Erasmus Medical Center


Verification Date

January 2021