None listed
Conditions
Interventions
Drug : Alpelisib: oral administration
In Phase lb, 200mg and 300mg once daily will be tested.
In Phase ll, the recommended phase ll dose (RP2D) in phase lb will be used.
Capecitabine: oral administr
Sponsors
Korea University Anam Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject has signed the Informed Consent Form (ICF) prior to any screening procedures being performed 2. male and female over 19 years old 3. At each phase of the trial, subjects who meet the following requirements in each phase will be enrolled. Phase Ib: Subjects with a histologically-confirmed, advanced/recurrent solid tumor who have progressed on standard therapy or whose disease does not have established standard therapy and not limited to PIK3CA mutation Phase II: Subjects with histologically confirmed, PIK3CA mutated, metastatic colorectal cancer that have progressed after treatment with two prior standard chemotherapeutic agents with targeted agents such as cetuximab, bevacizumab, aflibercept (Tissue samples of colorectal cancer patients must contain just PIK3CA gene alterations. e.g. single nucleotide variants, small indels, amplifications, structural variation etc. using targeted panel sequencing.) 4. Patient has evaluable disease as per RECIST 1.1. (Measurable lesions are not mandatory for study inclusion.) 5. ECOG performance status 0-1 6. Patient has adequate bone marrow and organ function as defined by the following laboratory values: - Absolute neutrophil count (ANC) = 1.5 x 109/L - Hemoglobin = 9.0 g/dL - Platelet = 100 x 109/L - Serum creatinine = ULN (upper limit of normal) or serum creatinine clearance > 50 mL/min - Total bilirubin: = 1.5 × ULN Subjects with a bile duct obstruction will be eligible if they meet the criteria after appropriate bile drainage; Patients with Gilbert syndrome should also be included after confirming that the total bilirubin level is = 1.5 x ULN in a follow-up screening test. - INR =1.5 - Potassium within normal limits, or corrected with supplements - Fasting Serum amylase = 2 × ULN - Fasting Serum lipase = ULN Phase Ib: Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) = 3 x ULN (regardless of liver metastases) Phase II: AST and ALT = 3 x ULN if liver metastases are absent, or AST and ALT = 5 x ULN if liver metastases are present. 7. Adequate cardiac function: QTc =480 msec; if QTc exceeds 480 msec, subjects can be enrolled if the average QTc value is less than 480 msec by measuring 3 times consecutively in total. 8. The subject is able to swallow and retain oral medication 9. Serum ß-HCG test negative within 14 days before the first administration of the study treatment (women of childbearing potential only). 10. Requirement for contraception must be observed by the subject. 11. Life expectancy of at least 3 months
Exclusion criteria
Exclusion criteria: 1. Patient has received previous treatment with a PI3K or AKT inhibitor. 2. Patient has received previous capecitabine in metastatic setting. 3. Patient has a known or suspicious hypersensitivity to fluoropyrimidines. 4. Patients with complete or partial dihydropyrimidine dehydrogenase deficiency. 5. Any cytotoxic chemotherapy from a previous treatment regimen within 14 days. If the subject received an investigational drug from another clinical trial, the subject can be enrolled after 2 weeks of last administration and more than 5 x half–life of the investigational drug. If monoclonal antibody therapy was given, the subject can be enrolled after four weeks after the last does. 6. Active central nervous system (CNS) lesions (i.e., those with radiologically unstable or symptomatic brain lesions). For those who receive radiation or surgical treatment, the subject can be enrolled if the subject is maintained without steroid therapy and the evidence of CNS disease progression for more than 4 weeks. However, patients with leptomeningeal metastases are excluded. 7. Patient has currently documented pneumonitis/interstitial lung disease 8. Patient has not recovered to = grade 1 (except alopecia) from related adverse effects of any prior anticancer therapy 9. Radiotherapy with a wide field (more than 30% of the bone marrow) of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment. 10. Patient who has undergone major surgery = 4 weeks prior to starting study treatment or who has not recovered from adverse effects of such procedure. 11. Patient has a clinically significant cardiac disease or impaired cardiac function, such as: - Acute coronary syndrome within the 6 months prior to the initiation of study drug (including myocardial infarction or unstable angina, Coronary Artery Bypass Graft surgery, percutaneous coronary intervention and stenting) - Heart failure = grade 2 by New York Heart Association (NYHA) functional classification or that requires treatment - Ejection fraction (EF) 160 mmHg or diastolic >100 mmHg with or without anti-hypertensive medication. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening. - Current or past history of clinically significant cardiac arrhythmia, atrial fibrillation, and/or conduction abnormality (e.g. congenital long QT syndrome, complete AV block) - On screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or corrected QT (QTcF) >450 msec for males and >460 msec for females (using Fridericia’s correction). All as determined by screening ECG (mean of triplicate ECGs). - Any risk factors that prolong QTc or increase the probability of arrhythmia, including medication (e.g. heart failure, hypokalemia, congenital long QT syndrome, history of Torsades de Pointes) 12. If the subject was diagnosed with diabetes (irrespective of treatment or symptom) or if the subject has impaired glucose tolerance (with blood glucose of 140-199 mg/dL after 2 hour oral glucose tolerance test (75g)), previous history of gestational diabetes, or steroid-induced diabete
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PFS, Progression Free Survival | — |
Secondary
| Measure | Time frame |
|---|---|
| ORR, Objective Response Rate | — |
Countries
Korea, Republic of
Contacts
Public Contactsoohyeon lee
Korea University Anam Hospital
Outcome results
None listed