A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics (PK) of TAK-228 as Single Agent in Adult East Asian Participants With Advanced Nonhematological Malignancies
Condition: Advanced Nonhematological Neoplasms
MeSH terms: Neoplasms
Intervention: TAK-228
Intervention description: TAK-228 Capsules.
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 28.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      The purpose of this study is to evaluate the safety and tolerability, recommended phase 2
      dose (RP2D), and to characterize PK of TAK-228 administered once daily or once weekly to East
      Asian participants with advanced nonhematological malignancies.
    

Eligibility criteria:

        Inclusion Criteria:

          1. With advanced nonhematologic malignancies, with the exception of primary brain tumor,
             and have failed or are not eligible for standard of care therapy. History of brain
             metastasis may be allowed if all of the following criteria are met:

               -  Brain metastases have been treated.

               -  There is no evidence of progression or hemorrhage after treatment.

               -  Steroid has been discontinued for >=4 weeks before the first dose of study drug.

               -  There is no ongoing requirement for steroids or anti-epileptic drugs.

          2. Received not more than 4 prior lines of systemic cytotoxic chemotherapy for advanced
             or metastatic disease.

          3. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

          4. Screening clinical laboratory values as specified below:

               -  Bone marrow reserve consistent with absolute neutrophil count (ANC) >=2000 per
                  cubic millimeter (/mm^3), platelet count >=125,000/mm^3, and hemoglobin >=10 gram
                  per deciliter (g/dL) without transfusion in the last 4 weeks.

        Note: Prophylactic transfusions of blood products or any prophylactic use of hematopoietic
        growth factors (such as erythropoietin, thrombopoietin, granulocyte colony stimulating
        factor [G-CSF], and granulocyte macrophage colony stimulating factor [GM-CSF]) is not
        permitted during the screening period.

          -  Hepatic: Total bilirubin less than or equal to (<=) 1.5*upper limit of normal (ULN),
             alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <=2.5*ULN (<=5*ULN if
             their elevation can be reasonably ascribed to the presence of hepatocellular
             carcinoma, biliary tract cancer, or metastatic disease in liver).

          -  Adequate renal function, defined as meeting any 1 of the following criteria:

               1. Serum creatinine <1.5*ULN.

               2. Creatinine clearance based on the Cockcroft-Gault estimate >=40 milliliter per
                  minute (mL/min).

               3. Creatinine clearance based on urine collection (12- or 24-hour) >=40 mL/min.

               4. Metabolic: Glycosylated hemoglobin (hemoglobin A1c [HbA1c]) <=7%, fasting serum
                  glucose <=130 milligram per deciliter (mg/dL), and fasting triglycerides <=300
                  mg/dL.

        Exclusion Criteria:

          1. Diagnosis of primary brain tumor.

          2. Untreated brain metastasis or history of leptomeningeal disease or spinal cord
             compression.

          3. Failed to recover from the reversible effects of prior anticancer therapies with the
             exception of alopecia, and after-effects associated with prior tyrosine kinase
             inhibitor therapy, such as hair depigmentation, hypothyroidism, and/or splinter
             hemorrhage.

          4. Initiation of hematopoietic growth factors within 1 week before the first dose of
             study drug.

          5. Manifestations of malabsorption caused by prior gastrointestinal surgery,
             gastrointestinal disease, or for some other reason that may alter the absorption of
             TAK-228. In addition, participants with enteric stomata are also excluded.

          6. Poorly controlled diabetes mellitus defined as Hemoglobin A1c (HbA1c) greater than (>)
             7%; participants with a history of transient glucose intolerance caused by
             corticosteroid administration are allowed if all other eligibility criteria are met.

          7. Known human immunodeficiency virus infection.

          8. Known hepatitis B surface antigen (HBsAg) positive, or known or suspected active
             hepatitis C virus (HCV) infection. Note: Participants who have isolated positive
             hepatitis B core antibody (HBcAb) and/or hepatitis B surface antibody (HBsAb) (that
             is, in the setting of negative HBsAg) may be enrolled but must have an undetectable
             hepatitis B virus (HBV) viral load. Participants who have positive hepatitis C virus
             antibody (HCVAb) may be enrolled but must have an undetectable HCV viral load.

          9. Significant active cardiovascular or pulmonary disease before the first dose of study
             drug, including:

               -  Uncontrolled hypertension (that is, systolic blood pressure >180 millimeter of
                  mercury [mmHg]; diastolic blood pressure >95 mmHg).

               -  Pulmonary hypertension.

               -  Uncontrolled asthma or oxygen saturation less than (<) 90% by pulse oximetry on
                  room air.

               -  Significant valvular disease; severe regurgitation or stenosis by imaging
                  independent of symptom control with medical intervention; or history of valve
                  replacement.

               -  Medically significant (symptomatic) bradycardia.

               -  History of arrhythmia requiring an implantable cardiac defibrillator.

               -  Baseline prolongation of the rate corrected QT interval (QTc) (example, repeated
                  demonstration of QTc interval >480 millisecond [ms], or history of congenital
                  long QT syndrome, or torsades de pointes).

         10. Diagnosed or treated for another malignancy within 2 years before the first dose or
             previously diagnosed with another malignancy and have any evidence of residual
             disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type
             are not excluded if they have undergone complete resection.