Combination Chemotherapy Plus Panitumumab or Bevacizumab for Inoperable Cholangiocarcinoma Without KRAS Mutations

Study Overview
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Brief Summary
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The purpose of this study is to determine the rate of progression free survival of patients with inoperable cholangiocarcinoma 6 months after enrollment in the study. The patients are treated with combination chemotherapy supplemented by biological agents panitumumab or bevacizumab.

Official Title
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Randomized Phase II Trial of Combination Chemotherapy With Panitumumab or Bevacizumab for Patients With Inoperable Cholangiocarcinoma Without KRAS Mutations

Conditions
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Cholangiocarcinoma

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically verified adenocarcinoma arisen from gall bladder, extra- or intrahepatic bile ducts or malignant cells consistent with the above and simultaneous radiologic findings consistent with cholangiocarcinoma Minimum 18 years of age Curative treatment currently not an option (operation, stereotactic radiation treatment or similar) KRAS analyzed and found wild-type (wt) Performance status 0-2 Evaluable disease according to RECIST, i.e. the disease need not be measurable Hematology: ANC ≥1.5x10^9/l. Thrombocytes ≥ 100x10^9/l Biochemistry: Bilirubinemia ≤ 3 x upper normal level. ALAT ≤ 5 x upper normal level. Creatinine ≤ upper normal level. At raised creatinine level the measured or calculated GFR must be at least 50% of the lower normal level Fertile women must present a negative pregnancy test and use secure birth control during and 6 months after treatment. Men with fertile partners must also take care of secure birth control. Written and orally informed consent Exclusion Criteria: Previous cytostatic treatment of inoperable cholangiocarcinoma Adjuvant or neoadjuvant chemotherapy, radiation therapy or immunotherapy within 4 weeks prior to treatment start Other concomitant experimental treatment Severe medical disease such as considerable heart disease, serious active infection or other disease making the patient unfit for study participation as assessed by investigator Other malignant disease within 5 years prior to enrolment except from non-melanotic skin cancer and carcinoma in situ cervicis uteri Interstitial pneumonitis or subsequent pulmonary fibrosis Pregnant or breastfeeding women Large-scale surgical intervention, excision biopsy or significant traumatic lesions within 28 days prior to treatment start or presumption that large-scale surgery will become necessary during study treatment. Significant non-healing wound or ulcers Active hemorrhage or increased risk of hemorrhage (e.g. tumor invasion in large vessels or known esophagus varices) Known hypersensitivity to panitumumab, bevacizumab or any of the auxiliary agents Grade IV fistulas Uncontrolled hypertension, i.e. symptomatic hypertension or non-medically stabilized hypertension >160/100 Haemoptysis > 2.5 ml within 2 weeks prior to enrolment Previous serious and unexpected reactions or know hypersensitivity to two or more of the applied cytostatics

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination chemotherapy + panitumumab<br> | Drug: Gemcitabine<br>* 1,000 mg/m2 on day 1 of a 2 weeks cycle<br>Drug: Oxaliplatin<br>* 60 mg/m2 on day 1 of a 2 weeks cycle<br>Drug: Capecitabine<br>* 1,000 mg/m2 x 2 daily on days 1-7 of a 2 weeks cycle<br>Drug: Panitumumab<br>* 6 mg/kg on day 1 of a 2 weeks cycle<br>|
| Experimental: Combination chemotherapy + bevacizumab<br> | Drug: Gemcitabine<br>* 1,000 mg/m2 on day 1 of a 2 weeks cycle<br>Drug: Oxaliplatin<br>* 60 mg/m2 on day 1 of a 2 weeks cycle<br>Drug: Capecitabine<br>* 1,000 mg/m2 x 2 daily on days 1-7 of a 2 weeks cycle<br>Drug: Bevacizumab<br>* 10 mg/kg on day 1 of a 2 weeks cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The fraction of patients alive and without progression at 6 months |  | 6 months from enrollment date | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate before cross-over |  | 6 months after enrollment or earlier in case of progression | 
| Overall survival |  | 6 months | 
| Progression free survival and response rate after cross-over |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cholangiocarcinoma, Inoperable, KRAS mutation, Biological treatment, Combination chemotherapy, Monoclonal antibody