Clinical Trial: Cabozantinib (XL-184) Monotherapy for Advanced Cholangiocarcinoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II Study of Cabozantinib (XL-184) Monotherapy in Patients With Advanced Cholangiocarcinoma After Progression on First or Second Line Systemic Therapy

Brief Summary:

This research study is evaluating a drug called cabozantinib as a possible treatment cancer of the bile duct. Cabozantinib is a drug that targets specific pathways inside the cells of the body. By blocking the c-MET and VEGFR2 pathways from sending signals, cabozantinib may prevent cells from multiplying. This drug has been used in other research studies and information from those other research studies suggests that this drug may help to stop the growth of bile duct cancer.

In this research study, the investigators are looking to see how well cabozantinib works in slowing the growth of bile duct cancer. The investigators are also assessing the safety and tolerability of cabozantinib in participants with this type of cancer.


Detailed Summary:

After the screening procedures confirm that the participants are eligible to participate in the research study:

A two-stage design will be employed in this study where at least 9 of the 20 patients enrolled in the first stage need to be progression-free at 16 weeks before the second stage can proceed. If this criterion is met, an additional 24 patients will be enrolled in the second stage for a total of 44 patients in the study. Patients will be treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles. Tumor assessments will be performed every 8 weeks until documented disease progression by RECIST criteria or drug intolerance.

In this research study, the participant will be given a study drug-dosing diary for each treatment cycle. Each treatment cycle lasts 28 days (4 weeks), during which time the participant will be taking the study drug, cabozantinib daily. The diary will also include special instructions for taking the study drug(s).

The participant will continue to take cabozantinib for as long as it is tolerated without any unacceptable side effects and the cancer does not get worse.

The following tests and procedures will be done during the research study:

Cycle 1 - On days 1, 8 and 15

  • Medical History
  • Physical Exam including vital signs and height and weight
  • Performance Status
  • Review of side effects (day 8 and 15 only)
  • Routine blood tests (day 8 and 15 only)
  • TSH blood sample on day 1 on
    Sponsor: Massachusetts General Hospital

    Current Primary Outcome: Median Progression Free Survival (PFS) [ Time Frame: 2 Years ]

    To evaluate the median progression free survival (PFS) of cabozantinib in patients with advanced cholangiocarcinoma after progression on 1 or 2 prior systemic therapies.


    Original Primary Outcome: Evaluate the median progression free survival (PFS) of cabozantinib in patients with advanced cholangiocarcinoma after progression on 1 or 2 prior systemic therapies [ Time Frame: 2 Years ]

    Evaluate the median progression free survival (PFS) of cabozantinib in patients with advanced cholangiocarcinoma after progression on 1 or 2 prior systemic therapies


    Current Secondary Outcome:

    • Number of Patients With Adverse Events [ Time Frame: 2 Years ]
      Evaluate the number of patients with advanced cholangiocarcinoma being treated with cabozantinib who have adverse events during treatment
    • Objective Response Rate (ORR) [ Time Frame: 2 Years ]
      To evaluate the objective response rate (ORR) for patients with advanced cholangiocarcinoma receiving cabozantinib
    • Median Overall Survival (OS) [ Time Frame: 2 years ]
      To evaluate the median overall survival (OS) for patients with advanced cholangiocarcinoma receiving cabozantinib


    Original Secondary Outcome:

    • Number of Patients With Adverse Events [ Time Frame: 2 Years ]
      Evaluate the number of patients with advanced cholangiocarcinoma being treated with cabozantinib who have adverse events during treatment
    • Evaluate the objective response rate (ORR) and median overall survival (OS) for in patients with advanced cholangiocarcinoma receiving cabozantinib [ Time Frame: 2 Years ]
      Evaluate the objective response rate (ORR) and median overall survival (OS) for in patients with advanced cholangiocarcinoma receiving cabozantinib
    • Evaluate the ORR, PFS and OS of subgroups stratified by tumor c-MET expression in a pre-planned post-hoc analysis. c-MET overexpression will be defined as > 50% of tumor cells with ≥ 2+ staining of c-MET by immunohistochemistry [ Time Frame: 2 Years ]
      Evaluate the ORR, PFS and OS of subgroups stratified by tumor c-MET expression in a pre-planned post-hoc analysis. c-MET overexpression will be defined as > 50% of tumor cells with ≥ 2+ staining of c-MET by immunohistochemistry
    • Explore molecular correlates of response, including circulating biomarkers and tumor tissue biomarkers [ Time Frame: 2 Years ]
      Explore molecular correlates of response, including circulating biomarkers and tumor tissue biomarkers


    Information By: Massachusetts General Hospital

    Dates:
    Date Received: September 24, 2013
    Date Started: September 2013
    Date Completion:
    Last Updated: December 12, 2016
    Last Verified: December 2016