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

NCT ID: NCT03370302

Last Updated: 2023-02-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-17
• Study Completion Date: 2019-08-28

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 participants with advanced nonhematological malignancies.

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 not available or is no longer effective. This study will assess the safety, tolerability, PK and will determine the RP2Ds of TAK-228.

The study will enroll approximately 46 participants, including at least 6 Japanese participants at RP2D dose level. Participants will be assigned to one of the following treatment arms:

• TAK-228 Once Daily
• TAK-228 Once Weekly

This multi-center trial will be conducted in South Korea, Taiwan, and Japan. The overall time to participate in this study is up to 12 months, unless in the opinion of the investigator and sponsor the participant would derive benefit from continued therapy beyond 12 months. Participants will be followed for 30 days after last dose of study drug for a follow-up assessment.

Conditions

Advanced Nonhematological Neoplasms

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

TAK-228 Once Daily

TAK-228, milled capsule, orally, once daily, on an empty stomach in a 28-day treatment cycle for up to 12 months or until disease progression or unacceptable toxicity or withdrawal of consent with a starting dose of 2 milligram (mg) in Cohort 1. Dose escalation will follow a standard 3+3 schema. If 2 mg, once daily, is safe and tolerable, then the dose will be escalated to 4 mg, once daily, until RP2D is determined.

Group Type: EXPERIMENTAL

TAK-228

Intervention Type: DRUG

TAK-228 Capsules.

TAK-228 Once Weekly

TAK-228, milled capsule, orally, once weekly, on an empty stomach in Cycle 1 of a 28-day treatment cycle and following a light meal from Cycle 2 for up to 12 months or until disease progression or unacceptable toxicity or withdrawal of consent with a starting dose of 20 mg in Cohort 1. Dose escalation will follow a standard 3+3 schema. If 20 mg, once weekly, is safe and tolerable, then the dose will be escalated to 30 mg, once weekly, until RP2D is determined.

Group Type: EXPERIMENTAL

TAK-228

Intervention Type: DRUG

TAK-228 Capsules.

Interventions

TAK-228

TAK-228 Capsules.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Calithera Biosciences, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan

National Cancer Center Hospital

Chūōku, Tokyo-To, Japan

Asan Medical Center

Seoul, , South Korea

National Taiwan-University Hospital

Taipei, , Taiwan

Countries

Japan; South Korea; Taiwan

References

Shimizu T, Kuboki Y, Lin CC, Yonemori K, Yanai T, Faller DV, Dobler L, Gupta N, Sedarati F, Kim KP. A Phase 1 Study of Sapanisertib (TAK-228) in East Asian Patients with Advanced Nonhematological Malignancies. Target Oncol. 2022 Jan;17(1):15-24. doi: 10.1007/s11523-021-00855-w. Epub 2021 Nov 29.

Reference Type: DERIVED

PMID: 34843044 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1202-4296

Identifier Type: REGISTRY

Identifier Source: secondary_id

1066064639

Identifier Type: REGISTRY

Identifier Source: secondary_id

20170270241

Identifier Type: OTHER

Identifier Source: secondary_id

JapicCTI-183822

Identifier Type: REGISTRY

Identifier Source: secondary_id

C31008

Identifier Type: -

Identifier Source: org_study_id