Lacosamide  tumor-derived DNA was assessed for seven mutations in codons 12 and 13 by a predeveloped kit and only wild type was included. The patients had to have evaluable disease, i.e. the disease need not be measurable, adequate bone marrow, and renal function. Hyperbilirubinemia was allowed up to three times the upper limit of normal and alanine transaminase up to five times the upper limit of normal. Chemotherapy, radiotherapy, or immunotherapy was allowed only as (neo-)adjuvant therapy and not within 4 weeks before inclusion. Ineligibility criteria included pregnancy or breast feeding, serious concomitant medical illness, other serious malignancy within 5 years, neuropathy of grade 2 or more, known hypersensitivity to any of the active or auxiliary substances, or pulmonary pneumonitis.

The study was approved by the regional ethical committee and was conducted in Baicalein accordance with the Declaration of Helsinki. The patients received oral and written information and were offered at least 1 day for reflection before giving a written informed consent. The trial was registered at ClinicalTrials.gov with the identifier NCT00779454. The study was an open-label phase II trial. It was run in parallel with a phase II study for patients with KRAS-mutated tumors receiving combination chemotherapy alone. This parallel trial is ongoing and results will be reported later.The trial was conducted according to good clinical practice guidelines and monitored by an purchase AMN-107 independent monitoring unit. Inclusion criteria and response evaluations were monitored in every patient while other data were monitored in every three patients.All patients with biliary tract cancer were potential candidates for the protocol and were screened with medical history, physical examination, recording of performance status, computed tomography scan of chest and abdomen, blood chemistries, blood counts, and KRAS evaluation. A screening log was recorded.

During treatment, blood counts were repeated before every treatment, blood chemistries and evaluation of toxicity were repeated at every 4 weeks, and physical examination, evaluation of performance status, and tumor evaluation were repeated every third cycle. If treatment was stopped before progression, the patient was followed clinically and order AMN-107 radiologically every 3 months until progression. After progression, only date and cause of death were recorded. Treatment after exclusion from the study was according to the department’s guidelines. The purpose of the present trial was to evaluate the efficacy of chemotherapy and panitumumab in patients with biliary tract cancer. We designed a marker-driven phase II trial directing only KRAS wild-type tumors to the treatment. This approach has never been used before and therefore we chose a two-stage design with stopping rules and included the minimum of patients that would allow a reasonable efficacy estimate.

Some of the disadvantages of single-arm phase II studies are the high risk of selection bias and the low external validity and therefore comparisons of efficacy data between basal lamina studies should be done with caution. We found that the primary end point was 74.2% PFS at 6 months. Secondary end points were an RR of 33% and median PFS and OS of 8.3 and 10.0 months, respectively.