biliary tract cancer Biliary tract cancer, intrahepatic bile duct cancer, extrahepatic bile duct cancer, cholangiocarcinoma, papillary cancer
Conditions
Interventions
One cycle: 7 days (Day 1-4: Oral administration of capivasertib at 400 mg twice daily, Day 5-7: Drug holiday (7 days [1 week]/1 cycle)), with a maximum of 18 cycles conducted
capivasertib
Sponsors
Sugimori Makoto
Maeda Shin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients meeting all of the following criteria will be eligible for inclusion: 1)Diagnosed with biliary tract cancer (via cytological or histological diagnosis) that is either unresectable or recurrent. 2)Aged 18 years or older. 3)Has undergone cancer genomic profiling, identifying at least one pathogenic alteration in PIK3CA, AKT1, or PTEN. In cases where the pathogenicity of a genetic alteration is unclear or its detection frequency is very low, a comprehensive assessment will be made based on the findings of an expert panel that evaluates treatment options associated with the genomic profiling. 4)Has undergone cancer genomic profiling and has not been identified with pathogenic genetic alterations in EGFR, HER2, KRAS, NRAS, HRAS, BRAF, TSC1, TSC2, pathogenic FGFR2 fusion genes with companion diagnostics, NTRK1, NTRK2, NTRK3 fusion genes, or RET fusion genes. Similar to above, ambiguous pathogenicity or low-frequency detections will be reviewed comprehensively by an expert panel. 5)Has undergone first-line therapy and demonstrated resistance. 6)If TMB-H or MSI-H results were obtained in genomic profiling, the patient must have been treated with pembrolizumab, a companion diagnostic drug, and shown resistance or intolerance. 7)Has no prior treatment history with AKT inhibitors across all cancer types. 8)Has no symptomatic metastasis to the central nervous system (brain, spinal cord, meninges). 9)Has measurable lesions based on RECIST Guidelines Version 1.1. 10)ECOG Performance Status of 0 or 1. 11)No history of blood transfusion or G-CSF administration within 7 days before testing. Laboratory values within 14 days prior to enrollment must meet all the following criteria (results from the same day as transfusion or G-CSF administration are acceptable): 1. Neutrophil count 1500 per mm3 or higher 2. Hemoglobin 9.0 g/dL or more 3. Platelet count 100,000 per mm3 or higher 4. Total bilirubin less than or equal to 1.5 mg /dL 5. AST (GOT) less than or equal to 100 IU/L ( less than or equal to 200 IU /L in case of liver metastasis) 6. ALT (GPT) less than or equal to 100 IU/L ( less than or equal to 200 IU /L for liver metastasis) 7. Serum creatinine less than 1.5 mg /dL. If serum creatinine exceed 1.5 mg/dL, the patient is eligible if the creatinine clearance (CCr)*1 exceeds 40 mL/min. *: Measured CCr by 24-hour urine collection or calculated using the Cockcroft-Gault estimation formula. Men CCr = (140 - age) x weight (kg) / 72 / serum creatinine level (mg /dL) Women CCr = 0.85 x (140 - age) x body weight (kg) / 72 / serum creatinine level (mg /dL) 12)Does not have Type 1 diabetes. 13)For Type 2 diabetes patients, insulin therapy is not required, and blood glucose is controlled with HbA1c level of less than 8.0% and a fasting blood glucose level of 160 mg/dL or less. 14)Has no history of administration of cautionary drugs (e.g., CYP3A inhibitors, CYP3A inducers, CYP3A substrates, MATE1, MATE2-K, or OCT2 substrates) within the past two weeks. 15)Has provided written informed consent after receiving a full explanation of the study. 16)Is capable of receiving outpatient treatment.
Exclusion criteria
Exclusion criteria: 1)Cancer genome profiling tests have been conducted, identifying pathogenic genetic alterations in EGFR, HER2, KRAS, NRAS, HRAS, BRAF, TSC1, and TSC2; pathogenic FGFR2 fusion genes with companion diagnostics; and NTRK1, NTRK2, NTRK3, and RET fusion genes. When there is disagreement about whether a genetic alteration is pathogenic or if its frequency is rare, a comprehensive judgment is made based on the results of an expert panel that reviews treatment options associated with the cancer genome profiling tests. 2)The patient has a history of treatment with AKT inhibitors. 3)The patient has symptomatic metastases to the central nervous system (brain, spinal cord, or meninges). 4)The patient has active multiple primary cancers. 5)The patient has localized infections requiring treatment or systemic active infections. 6)The patient is deemed unable to participate in the trial due to clinically significant psychiatric disorders. 7)The patient has interstitial pneumonia/pulmonary fibrosis, untreated and uncontrolled thrombosis (e.g., deep vein thrombosis, pulmonary embolism), or other severe complications as determined by the attending physician. 8)The patient meets any of the following cardiac criteria: (a) Mean resting corrected QTcF > 470 msec. (b) A history of QT prolongation induced by other medications. (c) A family history of long QT syndrome within second-degree relatives. (d) The presence of symptomatic or treatment-requiring arrhythmias, such as multifocal premature ventricular contractions, bigeminy, trigeminy, or ventricular tachycardia. (e) Symptomatic or treatment-resistant and uncontrolled atrial fibrillation. (f) Clinically significant abnormalities in conduction or waveform observed in a resting ECG, such as complete left bundle branch block or third-degree atrioventricular block. (g) A history of any of the following procedures or conditions within the past six months: coronary artery bypass grafting, angioplasty, vascular stenting, myocardial infarction, unstable angina, or congestive heart failure classified as New York Heart Association (NYHA) grade 2 or higher. (h) Uncontrolled hypotension. (i) Uncontrolled hypertension. (j) Other severe cardiac conditions. 9)The patient is HBs antigen-positive. 10)The patient is HBs antigen-negative but HBc antibody-positive and/or HBs antibody-positive, and HBV-DNA real-time PCR quantification method is 20 IU/mL (1.3 Log IU/mL) or more. 11)The patient has type 1 diabetes. 12)The patient has type 2 diabetes requiring insulin therapy. 13)The patient has type 2 diabetes with an HbA1c level is 8.0% or more. 14)The patient has type 2 diabetes with fasting blood glucose levels is 160 mg/dL or more. 15)The patient has a history of taking medications requiring caution (e.g., CYP3A inhibitors, CYP3A inducers, CYP3A substrates, MATE1, MATE2-K, and OCT2 substrates) within 2 weeks. 16)The patient is pregnant, potentially pregnant, or planning to become pregnant during the treatment period. 17)The patient participated in a clinical trial or study of a drug or medical device within 30 days before enrollment in this study. 18)The patient received any of the following treatments within the specified periods before enrollment in this study: 1.Cytotoxic anticancer drugs administered within 2 weeks before enrollment. 2.Prior treatments (chemotherapy, molecularly targeted therapies, antibody therapies, hormonal therapies, immunotherapies, radiation therapies) administered within 2 weeks before enrollmen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| objective response rate | — |
Secondary
| Measure | Time frame |
|---|---|
| Tumor control rate Progression-free survival Overall Survival Adverse event rate | — |
Contacts
Public ContactAkane Hirotani
Yokohama City University Medical Center
Outcome results
None listed