Advanced Nonhematological Neoplasms
Conditions
Interventions
investigational material(s)
Generic name etc : TAK-228
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material
Sponsors
Takeda Pharmaceutical Company Limited
Millennium Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion 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 (=40 milliliter per minute (mL/min). c) Creatinine clearance based on urine collection (12- or 24-hour) >=40 mL/min. d) Metabolic: Glycosylated hemoglobin (hemoglobin A1c [HbA1c]) <=7%, fasting serum glucose <=130 milligram per deciliter (mg/dL), and fasting triglycerides <=300 mg/dL.
Exclusion criteria
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 (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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety Number of Participants with Treatment Emergent Adverse Events (TEAEs) Timeframe; Baseline up to 30 days after the last dose of study drug (up to Cycle 12 Day 58) (Cycle length= 28 days) safety Number of Participants with Grade 3 or Higher TEAEs Timeframe; Baseline up to 30 days after the last dose of study drug (up to Cycle 12 Day 58) (Cycle length= 28 days) Adverse Event (AE) Grades will be evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), version 4.03. Grade 1 scaled as Mild; Grade 2 scaled as Moderate; Grade 3 scaled as severe or medically significant but not immediately life-threatening; Grade 4 scaled as life-threatening consequences; and Grade 5 scaled as death related to AE. safety Number of Participants with Serious TEAEs Timeframe; Baseline up to 30 days after the last dose of study drug (up to Cycle 12 Day 58) (Cycle length= 28 days) safety Number of Participants with Dose-limiting Toxicities (DLTs) during Cycle 1 Timeframe; Baseline up to Day 28 in Cycle 1 (Cycle length= 28 days) safety Number of Participants with TEAEs Leading to Study Drug Discontinuation Timeframe; Baseline up to 30 days after the last dose of study drug (up to Cycle 12 Day 58) (Cycle length= 28 days) pharmacokinetics Cmax: Maximum Observed Plasma Concentration for TAK-228 on Cycle 1 Day 1 Timeframe; Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) pharmacokinetics Cmax: Maximum Observed Plasma Concentration for TAK-228 on Cycle 1 Day 15 Timeframe; Cycle 1 Day 15 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) pharmacokinetics Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-228 on Cycle 1 Day 1 Timeframe; Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length= 28 days) pharmacokinetics Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-228 on Cycle 1 Day 15 Timeframe; Cyc | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Clinical Benefit Rate Timeframe; Baseline up to 1 Year 7 Months The Clinical Benefit Rate (CBR) was defined as the percentage of participants with a best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD). BOR was defined as the best response recorded after the first dose of study drug until subsequent therapy. As per Response Evaluation Criteria Solid Tumors (RECIST) version 1.1 guidelines, CR was defined as disappearance of all target lesions and non-target lesions, and normalization of tumor marker level. PR was defined as >= 30% decrease in the sum of the longest diameter (LD) of target lesions, no progression in non-target lesion, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression (PD). PD was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | — |
Countries
Japan, Republic of Korea, Taiwan
Outcome results
None listed