None listed
Conditions
Interventions
Drug :
• Phase IB is planned for a 4-stage dose level and the traditional 3 + 3 design is applied. Three subjects will be enrolled at each dose level, and if there is no dose limiting toxicity (DLT)
Sponsors
Seoul National University Bundang 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. Age = 20 years old of male and female 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. * Phase II: Subjects with histologically confirmed locally advanced or metastatic gastric cancer that have progressed after treatment with first-line fluoropyrimidine-based chemotherapy (Tissue samples of gastric cancer must contain PIK3CA gene alterations (e.g. single nucleotide variants, small indels, amplifications, structural variations, etc.) identified by central or local next generation sequencing (NGS). If the subject received adjuvant chemotherapy after curative gastric resection and lymph node dissection, the adjuvant chemotherapy is considered to be the first-line palliative chemotherapy if the disease recurred during adjuvant chemotherapy or within 6 months after the completion of adjuvant chemotherapy. 4. Phase IB: Patient has evaluable disease as per RECIST 1.1. (Measurable lesions are not mandatory for study inclusion.) Phase II: Patient has at least one measurable lesion as per RECIST 1.1. 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 (by Cockcroft-Gault formula, or 24h urine collection) * 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. * 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. The subject is able to swallow and retain oral medication 8. Serum ß-HCG test negative within 14 days before the first administration of the study treatment (women of childbearing potential only). 9. Requirement for contraception must be observed by the subject.
Exclusion criteria
Exclusion criteria: 1. Patient has received previous treatment with a PI3K or AKT inhibitor. (Note: prior mTOR inhibitor treatment is allowed.) 2. Patient has a known or suspicious hypersensitivity to paclitaxel or other products containing Cremophor. 3. 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. 4. 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. 5. Patient has not recovered to = grade 1 (except alopecia) from related adverse effects of any prior antineoplastic therapy 1. Patient has received previous treatment with a PI3K or AKT inhibitor. (Note: prior mTOR inhibitor treatment is allowed.) 2. Patient has a known or suspicious hypersensitivity to paclitaxel or other products containing Cremophor. 3. 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. 4. 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. 5. Patient has not recovered to = grade 1 (except alopecia) from related adverse effects of any prior antineoplastic therapy 6. 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. 7. Patient who has undergone major surgery = 4 weeks prior to starting study treatment or who has not recovered from adverse effects of such procedure. 8. 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) 180 mmHg or diastolic >100 mmHg despite medical treatment • Current or past history of clinically significant ca
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine MTD(maximal tolerated dose), DLT(dose-limiting toxicity), and RP2D(recommended phase II dose) of alpelisib in combination with paclitaxel;progression-free survival rate at 4 months | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess safety, pharkacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of alpelisib in combination with paclitaxel;To assess overall survival (OS), progression-free survival (PFS), objective response rate (ORR; by RECIST v1.1), disease control rate, duration of response, time to response, and safety | — |
Countries
Korea, Republic of
Contacts
Public ContactOnah Kim
Seoul National University Bundang Hospital
Outcome results
None listed