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

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

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.

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