Combined Biological Treatment and Chemotherapy for Patients With Inoperable Cholangiocarcinoma

Study Overview
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Brief Summary
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The purpose of this study is partly to continue the good experience the investigators have with chemotherapy and partly to optimize treatment of inoperable cholangiocarcinoma by adding a biological antibody to the treatment of patients with wild-type Kirsten rat sarcoma viral oncogene homolog (KRAS).

Detailed Description
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Cholangiocarcinoma is a relatively rare disease. In Denmark approximately 150 patients are diagnosed each year. A small part of the patients can be offered surgery, but the operation will rarely be radical, and most patients with cholangiocarcinoma are therefore candidates for chemotherapy. In Denmark the combination therapy of Gemcitabine, Oxaliplatin and Capecitabine has been used in recent years. Based on experience with gastrointestinal tumors, however, there seems to be an effect of new biological substances, including EGFR antibodies. There are casuistic reports on the specific effect of a monoclonal antibody against EGFR in cholangiocarcinoma. The effect of EGF is mediated through an intracellular pathway involving the KRAS protein. It has been shown that a mutation of KRAS causes the EGF system to be constantly activated. Effect in patients with a KRAS mutation is therefore not to be expected. Approximately 50% of the patients present this mutation.

Official Title
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Combined Biological Treatment and Chemotherapy for Patients With Inoperable Cholangiocarcinoma

Conditions
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Cholangiocarcinoma

Intervention / Treatment
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* Drug: Gemcitabine, Oxaliplatin, Capecitabine,
* Drug: Panitumumab, Gemcitabine, Oxaliplatin, Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically verified adenocarcinoma arisen from gallbladder, extra or intrahepatic bile ducts or malignant cells consistent with the above and concomitant radiologic findings consistent with cholangiocarcinoma. Curative treatment presently discounted (surgery, stereotactic radiotherapy, etc.) KRAS analyzed and found wild-type (wt) or mutated PS 0-2 Evaluable disease according to RECIST criteria, i.e., the disease does not need to be measurable Haematology: ANC ≥ 1.5 x 10^9/l Thrombocytes ≥ 100x10^9/l Biochemistry: Bilirubinaemia ≤ 3 x upper normal value ALAT ≤ 5 x upper normal value Creatinin ≤ upper normal value. If raised creatinin, the measured or calculated GFR must be at least 50% of the lower normal value. Fertile women must present a negative pregnancy test and use birth control during and 3 months after treatment. The following methods are considered safe birth control: Birth control pills, coil, gestagen deposit injection, subdermal implantation, hormonal vagina ring, and transdermal deposit band-aid) Oral and written informed consent Exclusion Criteria: Chemotherapy within 4 weeks Radiotherapy within 4 weeks Immunotherapy within 4 weeks Other concomitant experimental treatment Known neuropathy ≥ grade 2 Serious congruous medical disease Other previous malignant disease within 5 years, excl. non-melanoma skin cancer and carcinoma in situ cervicis uteri Previous serious and unexpected reactions to fluoropyrimidine treatment Hypersensitivity to one or more of the active substances, auxiliary substances or fluoruracil Patients with interstitial pneumonitis or pulmonary fibrosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: KRAS wildtype<br> | Drug: Panitumumab, Gemcitabine, Oxaliplatin, Capecitabine<br>* Gemcitabine: 1,000 mg/m2 day 1 Oxaliplatin: 60 mg/m2 day 1 Capecitabine: 1,000 mg/m2 x 2 daily days 1-7 Panitumumab: 6 mg/kg day 1<br>|
| Other: KRAS mutation<br>Inclusion has been completed in the KRAS mutation arm. | Drug: Gemcitabine, Oxaliplatin, Capecitabine,<br>* Gemcitabin: 1,000 mg/m2 day 1 Oxaliplatin: 60 mg/m2 day 1 Capecitabine: 1,000 mg/m2 x 2 daily days 1-7<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  | 6 months | 
| Overall survival |  | 6 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KRAS wild-type, Cholangiocarcinoma, Inoperable