A Safety and Pharmacokinetic Study of TAK-228 in Combination With TAK-117 in Adult Participants With Advanced Nonhematologic Malignancies
Condition: Advanced Nonhematologic Malignancies
MeSH terms: Neoplasms
Intervention: TAK-228; TAK-117
Intervention description: TAK-228 Capsules; TAK-117 Capsules
Intervention MeSH terms: Serabelisib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 101.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug Therapy; TAK-228; TAK-117

Summary:

      The purpose of this study was to evaluate the safety and to determine dose-limiting
      toxicities (DLTs), maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), and
      dosing schedules of oral TAK-228+TAK-117. It also evaluated the single- and multiple-dose
      plasma pharmacokinetics (PK) of TAK-228+TAK-117 in participants with advanced nonhematologic
      malignancies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female participants 18 years or older

          -  Participants must have a diagnosis and documented disease progression of a solid tumor
             malignancy, excluding primary brain tumor, for which standard, curative, or life
             prolonging treatment does not exist or is no longer effective

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Female participants who are postmenopausal for at least 1 year prior to screening. For
             women of child-bearing potential agree to practice 2 effective methods of
             contraception or agree to practice true abstinence

          -  Male participants must agree to practice effective barrier contraception during the
             entire study treatment period and through 30 days after last dose of study drug or
             practice true abstinence

          -  Voluntary written consent

          -  Suitable venous access

          -  Participants must have a block of banked tumor tissue and/or fresh tumor tissue or at
             least 10 unstained slides available to be sent to the central laboratory

          -  Clinical laboratory values as specified in the protocol

          -  Participants must have radiographically or clinically evaluable tumor

        Exclusion Criteria:

          -  Female participants who are lactating and breastfeeding or have a positive serum
             pregnancy test during the Screening period or a positive urine pregnancy test on Day 1
             before first dose of study drug

          -  Any serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the completion of treatment

          -  Treatment with any investigational products within 30 days before the first dose of
             study drug

          -  Previous treatment with TAK-117 and/or TAK-228; previous treatment with dual mTORC1/2
             or dual PI3K-mTOR inhibitors

          -  Failed to have recovered from the reversible effects of previous anticancer therapies

          -  Have received systemic corticosteroid (inhalers are allowed) within 7 days before the
             first administration of study drug

          -  Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral
             absorption or tolerance of study drug

          -  Diagnosis of diabetes mellitus

          -  Other clinically significant co-morbidities, such as uncontrolled pulmonary disease,
             active CNS disease, active infection

          -  Known human immunodeficiency virus (HIV) infection

          -  Cardiovascular conditions as defined in the protocol

          -  A requirement for positive inotropic support (excluding digoxin) or serious
             uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation) within 1 year
             before screening

          -  Participants who are taking proton pump inhibitors within 7 days of the first dose or
             who require treatment with proton pump inhibitors during the trial or those who are
             taking histamine-2 (H2) receptor antagonists within 24 hours of the first dose

          -  Participants who received previous therapy with PI3K inhibitors or rapalogs will be
             allowed in the study if all other inclusion/exclusion criteria are met

          -  Diagnosis of primary brain tumor or symptomatic brain metastasis. Participants with
             brain metastases must be without neurologic dysfunction that would confound the
             evaluation of neurologic and other adverse events (AEs)