A Phase II Trial of LDK378 in ROS1 and /or ALK Over-expressed Advanced Intrahepatic or Hilar Cholangiocarcinoma

Sample size: LDK378 will be considered as an active agent and deserved for further development. Considering 10% dropout rate, total 34 patients will be included.

Step 1: LDK378 in suitable patients:

Collect tumor tissue for immunohistochemistry staining to confirm the status of ROS1 or ALK expression. If the patient fits all criteria, LDK378 750 mg ( p.o.) daily, with 3 week as a treatment cycle.

Step 2: Evaluation of tumor response according to RECIST 1.1 version

1. Evaluation will be done at baseline and every 6 weeks

2. Evaluation will be performed with CT or MRI and the response is defined as follows:

   • Complete response - the disappearance of all target lesions.
   • Partial response - at least a 30% decrease in the sum of the longest diameter of target lesions compared to the baseline sum longest diameter.
   • Progressive disease - at least a 20% increase in the sum of the longest diameter of target lesions compared to the smallest sum longest diameter recorded since the treatment started or the appearance of one, or more new lesions, or reappearance of any lesion that had disappeared, or clear worsening of any assessable disease, or appearance of any new lesion or site.
   • Stable disease - neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, compared to the smallest sum longest diameter since the treatment started