A Study of TAK-441 in Adult Patients With Advanced Nonhematologic Malignancies

Study Overview
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Brief Summary
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This is the first study in which TAK-441 is administered to humans. The patient population will consist of adults aged 18 or older who have advanced nonhematologic malignancies and for whom standard treatment is no longer effective or does not offer curative or life-prolonging potential. Following completion of the dose escalation study, patients will be enrolled as part of 2 expansion cohorts.

Official Title
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A Multicenter, Open-Label, Dose-Escalation, Phase 1 Study of TAK-441, an Oral Hedgehog Signaling Pathway Inhibitor, in Adult Patients With Advanced Nonhematologic Malignancies

Conditions
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Advanced Nonhematologic Malignancies, Carcinoma, Basal Cell

Intervention / Treatment
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* Drug: TAK-441


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Each patient must meet all of the following inclusion criteria to be enrolled in the study: Male or female 18 years or older Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 Diagnosis of a nonhematologic malignancy for which standard treatment is no longer effective or does not offer curative or life-prolonging potential Meet other clinical, radiographic or laboratory inclusion criteria as specified in the protocol Voluntary written consent Exclusion Criteria: Patients meeting any of the following exclusion criteria are not to be enrolled in the study: Life-threatening illness unrelated to cancer Receiving other treatment (radiotherapy, antineoplastics or investigational agents) within protocol specified windows of first dose of TAK-441 Patients with brain metastases who do not meet criteria specified in study protocol Known history of human immunodeficiency virus (HIV) infection, hepatitis B or hepatitis C Major surgery within 14 days before the first dose of TAK-441 Infection requiring systemic therapy, or other serious infection within 14 days of the first dose of TAK-441 Do not meet other clinical, laboratory or radiographic criteria as specified in the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAK-441<br> | Drug: TAK-441<br>* TAK-441 will be administered as an oral tablet as follows: Patients enrolled in the dose escalation cohorts will receive: A single-dose administration on Day 1, followed by a 1-week washout period during which pharmacokinetics is assessed Continuous daily dosing on Days 8 through 28 in Cycle 1 In subsequent cycles, continuous daily dosing over 21 days, repeated continuously Patients enrolled in the expansion cohorts will receive continuous daily dosing on Days 1 through 21 of each 21-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety profile, maximum tolerated dose (MTD) or maximum feasible dose (MFD) of TAK-441 administered as an oral formulation in patients wtih advanced nonhematologic malignancies | Adverse events, serious adverse events, dose-limiting toxicities, assessments of clinical laboratory values, electrocardiogram parameters and vital sign measurements | From first dose of TAK-441 through 30 days after the last dose of TAK-441 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single-dose and multiple-dose plasma pharmacokinetics (PK) of TAK-441 | Including but not limited to maximum plasma concentration (Cmax), first time to plasma concentration (Tmax) and area under the plasma concentration versus time curve (AUC) | Sampling during Cycle 1 (Days 1-28) | 
| Pharmacodynamic effect of TAK-441 on Gli 1 expression in skin |  | Cycle 1 Day 22 | 
| Pharmacodynamic effect of TAK-441 on Gli 1 expression in tumors (expansion cohorts only) |  | Cycle 1 Day 15 | 
| Antitumor activity of TAK-441 administered as a single-agent therapy based on investigators' assessments of tumor response in patients who have advanced basal cell carcinoma | Based on the investigator's assessment using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) | Days 15-21 of cycles 2, 4 and every fourth cycle thereafter; and end of study |