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

Carcinoma, Basal Cell Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01204073
• Other study ID #: C24002
• Secondary ID: 2010-021311-17
• Status: Completed
• Phase: Phase 1
• First received: September 15, 2010
• Last updated: July 1, 2013
• Start date: October 2010
• Est. completion date: January 2013

Study information

• Verified date: July 2013
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationEuropean Union: European Medicines Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: January 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Nonhematologic Malignancies
• Carcinoma, Basal Cell
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Premiere Oncology, A Medical Corporation	Santa Monica	California
United States	Mayo Clinic	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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)	No
Secondary	Pharmacodynamic effect of TAK-441 on Gli 1 expression in skin		Cycle 1 Day 22	No
Secondary	Pharmacodynamic effect of TAK-441 on Gli 1 expression in tumors (expansion cohorts only)		Cycle 1 Day 15	No
Secondary	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	No