Combination of AZD6738 Plus Durvalumab in Refractory Biliary Tract Cancer in Patients Who Have Failed Immunotherapy
This trial will enroll advanced biliary tract cancer patients who have been previously treated with immunotherapy in either the 2nd or 3rd line. Patients will be treated with AZD6738 and Durvalumab combination.
⁃ Written informed consent and any locally-required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
⁃ Age \> 20 years at time of study entry
⁃ Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
⁃ Life expectancy of \> 16weeks
⁃ Histologically proven BTC, including intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer, ampulla of vater cancer
⁃ Unresectable or recurrent
⁃ Failed immunotherapy for their advanced BTC (the patient may have also received chemotherapy in the 1 or 2L)
⁃ At least one measurable lesion that can be accurately assessed at baseline by computed tomography (CT) (magnetic resonance imaging \[MRI\] where CT is contraindicated) and is suitable for repeated assessment as per RECIST 1.1.
⁃ Body weight \>30kg
‣ Adequate normal organ and marrow function measured within 28 days prior to administration of study treatment as defined below :
• Haemoglobin ≥9.0 g/dL
∙ Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
∙ Platelet count ≥ 100x 109/L
∙ Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). (This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.)
∙ AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
∙ Patients must have creatinine clearance estimated of ≥51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test :
‣ Estimated creatinine clearance = (140-age \[years\]) x weight (kg) (x F)a serum creatinine (mg/dL) x 72 a where F=0.85 for females and F=1 for males.
‣ Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.
⁃ Postmenopausal is defined as:
• Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
• Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50
• radiation-induced oophorectomy with last menses \>1 year ago
• chemotherapy-induced menopause with \>1 year interval since last menses
• surgical sterilisation (bilateral oophorectomy or hysterectomy) 12. Male patients must use a condom during treatment and for 6 months after the last dose of AZD6738 when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception (\[see appendix H for acceptable methods\]) if they are of childbearing potential 13. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.