Cyberknife Radiosurgery Boost for Hilar Cholangiocarcinoma (Klatskin Tumor)

Brief Title

Cyberknife Radiosurgery Boost for Hilar Cholangiocarcinoma (Klatskin Tumor)

Official Title

Phase I Dose Escalation Trial of External Beam Radiation and Cyberknife Radiosurgery Boost With Concurrent Capecitabine for Hilar Cholangiocarcinoma (Klatskin Tumor)

Brief Summary

      The purpose of this study is to test the safety of giving external beam radiation, followed
      by a Cyberknife radiosurgery boost at different dose levels, together with a chemotherapy
      drug called capecitabine. The dose of Cyberknife radiosurgery boost will be made higher
      slowly in this protocol. Patients with hilar cholangiocarcinoma (Klatskin tumor), which is
      not amenable for surgical removal, are eligible.

      The hypothesis is that highly focused high dose radiation delivered using Cyberknife in
      conjunction with traditional radiation and chemotherapy can improve outcome in this patient
      population.
    

Detailed Description

      This is a dose escalation study which will escalate the dose of Cyberknife radiosurgery boost
      after external beam radiation of 45 Gy with concurrent capecitabine. The three dose levels
      are 4 Gy x5, 5 Gy x5 and 6 Gy x 5, with 3 patients at each dose level. Dose-limiting toxicity
      (DLT) is defined as acute grade 3 liver or intestinal toxicity or any acute grade 4 toxicity.
      If one patient experienced a DLT at a particular dose level, the cohort should be expanded to
      6 patients. The maximum tolerated dose (MTD) is defined as the dose level below that which
      results in DLT in 2 or more of the 6 patients in each cohort. At least 5 patients should be
      enrolled in the cohort of 6 Gy x 5 even if none of the first 3 experienced DLT, as a means of
      added verification of dose tolerance, at this upper limit of dose for this study.

      The patient population includes any patients who have unresectable hilar cholangiocarcinoma
      without any prior history of radiation. We anticipate accruing 1 patient every 2 months;
      therefore, we estimate that it will require approximately 22 months to accrue 11 patients if
      no DLT is experienced by any patients requiring expansion of the cohorts.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

To evaluate acute toxicities

Secondary Outcome

 To assess local and regional control

Condition

Cholangiocarcinoma

Intervention

External beam radiation and Cyberknife radiosurgery boost and capecitabine

Study Arms / Comparison Groups

 1
Description:  External beam radiation with Cyberknife radiosurgery boost and concurrent capecitabine

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

11

Start Date

October 2007

Completion Date

December 2008

Primary Completion Date

December 2008

Eligibility Criteria

        Inclusion Criteria:

          -  Age eighteen years or older

          -  Histological defined unresectable cholangiocarcinoma of hilar region of the liver

          -  Patients should have evaluable disease on one or more imaging modalities (CT scan,
             MRI, and/or PET) since this will be necessary for radiation treatment planning.
             However, because the borders of these tumors are sometimes difficult to define
             precisely, measurable disease is not required (see Section 9.1 for definitions of
             evaluable and measurable disease).

          -  The maximum tumor dimension should be less than 6 cm.

          -  Patients with pathologically enlarged perihepatic regional lymph nodes are allowed.

          -  Prior surgical resection is allowed if there is gross disease remaining

          -  Adjuvant chemotherapy is allowed at least 1 month after completion of radiation
             therapy if any grade 3 or higher toxicity has resolved

          -  Percutaneous biliary drains and biliary stents are allowed

          -  Performance status of ECOG 0-1 (see Appendix I)

          -  Life expectancy greater than 6 months

          -  Subject must have normal organ and marrow functions as defined below

               -  leukocytes >3,000/mcL

               -  absolute neutrophil count >1,500/mcL

               -  platelets >100,000/mcL

               -  total bilirubin <2.5 X institutional upper limit of normal

               -  AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal

               -  creatinine within normal institutional limits OR

               -  creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above
                  institutional normal.

               -  PT/PTT within normal institutional limits

          -  Gold marker seeds (1 to 3) are required to be placed in or around the primary tumor by
             an interventional radiologist

          -  Ability to give written informed consent and willingness to comply with the
             requirements of the protocol

          -  Women of child-bearing potential must agree to use an effective method of birth
             control during treatment and for six months after receiving their last dose of
             treatment

        Exclusion Criteria:

          -  Patients who have had prior chemotherapy

          -  Patients who have had external beam radiation to the region of liver hilar previously.

          -  Patients receiving any other investigational agents

          -  Patients with known metastases

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to capecitabine.

          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Patients who are not candidates for gold marker seeds placement due to position of the
             tumor or co-existing medical condition.

          -  Pregnant or lactating women and women of child-bearing potential who are not using an
             effective method of birth control

          -  Any condition that compromises compliance with the objectives and procedures of this
             protocol, as judged by the principal investigator
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Kim Huang, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00630890

Organization ID

07455


Responsible Party

Sponsor

Study Sponsor

University of California, San Francisco


Study Sponsor

Kim Huang, M.D., Principal Investigator, University of California, San Francisco


Verification Date

September 2015