Status:

TERMINATED

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

Lead Sponsor:

Calithera Biosciences, Inc

Conditions:

Advanced Nonhematological Neoplasms

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief 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 participan...

Detailed Description

The drug being tested in this study is called TAK-228. TAK-228 is being tested to treat East Asian participants with advanced nonhematological malignancies for whom standard anticancer treatment is no...

Eligibility Criteria

Inclusion

  • 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.
  • Received not more than 4 prior lines of systemic cytotoxic chemotherapy for advanced or metastatic disease.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
  • 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:
  • Serum creatinine \<1.5\*ULN.
  • Creatinine clearance based on the Cockcroft-Gault estimate \>=40 milliliter per minute (mL/min).
  • Creatinine clearance based on urine collection (12- or 24-hour) \>=40 mL/min.
  • Metabolic: Glycosylated hemoglobin (hemoglobin A1c \[HbA1c\]) \<=7%, fasting serum glucose \<=130 milligram per deciliter (mg/dL), and fasting triglycerides \<=300 mg/dL.

Exclusion

  • Diagnosis of primary brain tumor.
  • Untreated brain metastasis or history of leptomeningeal disease or spinal cord compression.
  • 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.
  • Initiation of hematopoietic growth factors within 1 week before the first dose of study drug.
  • 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.
  • 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.
  • Known human immunodeficiency virus infection.
  • 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.
  • 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).
  • 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.

Key Trial Info

Start Date :

January 17 2018

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

August 28 2019

Estimated Enrollment :

28 Patients enrolled

Trial Details

Trial ID

NCT03370302

Start Date

January 17 2018

End Date

August 28 2019

Last Update

February 8 2023

Active Locations (4)

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Page 1 of 1 (4 locations)

1

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan, 277-8577

2

National Cancer Center Hospital

Chūōku, Tokyo-To, Japan, 104-0045

3

Asan Medical Center

Seoul, South Korea, 05505

4

National Taiwan-University Hospital

Taipei, Taiwan, 100