None listed
Conditions
Interventions
Drug : Dosing schedule:
• Durvalumab 1500 mg iv on D1
• AZD6738 240 mg bid on D15-D28
Every 4 weeks
C1D1 dose of durvalumab will be delivered, and AZD6738 of 240 mg bid will be dosed at D15-D28. Ev
Sponsors
Seoul National University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent and any locally-required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations 2. Age > 20 years at time of study entry 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 4. Life expectancy of > 16weeks 5. Histologically proven BTC, including intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer, ampulla of vater cancer 6. Unresectable or recurrent 7. Failed immunotherapy for their advanced BTC (the patient may have also received chemotherapy in the 1 or 2L) 8. 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. 9. Body weight >30kg 10. 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. 11. 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.
Exclusion criteria
Exclusion criteria: 1. Participation in another clinical study with an investigational product during the last 3 weeks 2. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication. 3. Any previous treatment with ATR inhibitor 4. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study 5. Receipt of the last dose of anti-cancer therapy (chemotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) within 21 days of the first dose of study drug .2 The minimum washout period for immunotherapy is 42 days 6. Mean QT interval: Mean resting corrected QT interval (QTc) >470 msec for females and >450 for men, obtained from 3 electrocardiograms (ECGs) 2-5 minutes apart using the Fredericia formula - Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as congestive heart failure, unstable angina pectoris, acute myocardial infarction, hypokalaemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death under 40 years of age, conduction abnormality not controlled with pacemaker or medication. 7. Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. The following are exceptions to this criterion The following are exceptions to this criterion: - Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) - Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent - Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) 8. Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria ? Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. ? Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician. 9. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 10. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug 11. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. Patients must have recovered from any effects of any major surgery 12. History of allogenic organ transplantation. 13. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease control rate(DCR) | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free survival(PFS);Overall survival(OS);Objective response rate(ORR);Duration of response(DoR);Percentage change from baseline in tumor size;Best percentage change from baseline in tumor size;Toxicity(CTCAE v5.0) | — |
Countries
Korea, Republic of
Contacts
Public ContactEunkyung Kim
Seoul National University Hospital
Outcome results
None listed