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

Sponsor

Millennium Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01204073

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Nonhematologic Malignancies Carcinoma, Basal Cell	Drug: TAK-441	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2010

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAK-441	Drug: TAK-441 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

Arm

Intervention/Treatment

Experimental: TAK-441

Drug: TAK-441

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

Outcome Measures

Primary Outcome Measures

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 [From first dose of TAK-441 through 30 days after the last dose of TAK-441]
Adverse events, serious adverse events, dose-limiting toxicities, assessments of clinical laboratory values, electrocardiogram parameters and vital sign measurements

Secondary Outcome Measures

Single-dose and multiple-dose plasma pharmacokinetics (PK) of TAK-441 [Sampling during Cycle 1 (Days 1-28)]
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)
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 [Days 15-21 of cycles 2, 4 and every fourth cycle thereafter; and end of study]
Based on the investigator's assessment using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Scottsdale	Arizona	United States	85259-5499
2	Premiere Oncology, A Medical Corporation	Santa Monica	California	United States	90404

Sponsors and Collaborators

Millennium Pharmaceuticals, Inc.

Investigators

Study Director: Medical Monitor, Millennium Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Millennium Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT01204073

Other Study ID Numbers:

C24002
2010-021311-17

First Posted:

Sep 17, 2010

Last Update Posted:

Jul 2, 2013

Last Verified:

Jul 1, 2013

Additional relevant MeSH terms:

Neoplasms

Carcinoma, Basal Cell

Study Results

No Results Posted as of Jul 2, 2013