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

Purpose

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	Intervention	Phase
Advanced Nonhematologic Malignancies Carcinoma, Basal Cell	Drug: TAK-441	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Millennium Pharmaceuticals, Inc.:

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 [ Time Frame: From first dose of TAK-441 through 30 days after the last dose of TAK-441 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Sampling during Cycle 1 (Days 1-28) ] [ Designated as safety issue: No ]
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 [ Time Frame: Cycle 1 Day 22 ] [ Designated as safety issue: No ]
Pharmacodynamic effect of TAK-441 on Gli 1 expression in tumors (expansion cohorts only) [ Time Frame: Cycle 1 Day 15 ] [ Designated as safety issue: No ]
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 [ Time Frame: Days 15-21 of cycles 2, 4 and every fourth cycle thereafter; and end of study ] [ Designated as safety issue: No ]
Based on the investigator's assessment using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)

Estimated Enrollment:	46
Study Start Date:	October 2010
Estimated Study Completion Date:	January 2013
Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Arms

Assigned Interventions

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01204073

Locations

United States, Arizona
Mayo Clinic
Scottsdale, Arizona, United States, 85259-5499
United States, California
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.

More Information

No publications provided

Responsible Party:	Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT01204073 History of Changes
Other Study ID Numbers:	C24002, 2010-021311-17
Study First Received:	September 15, 2010
Last Updated:	January 23, 2013
Health Authority:	United States: Food and Drug Administration European Union: European Medicines Agency

Additional relevant MeSH terms:

Neoplasms
Carcinoma
Carcinoma, Basal Cell

Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Basal Cell

ClinicalTrials.gov processed this record on May 23, 2013