A Safety and Pharmacokinetic Study of TAK-228 in Combination With TAK-117 in Adult Participants With Advanced Nonhematologic Malignancies

• Status: Completed
• Trial end date: 2018-04-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Millennium Pharmaceuticals, Inc.
• Treatments: Serabelisib

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)