Study of TAK-733 in Adult Patients With Advanced Nonhematologic Malignancies

A Multicenter, Open-label, Dose-escalation, Phase I Study of TAK-733, an Oral MEK Inhibitor, in Adult Patients With Advanced Nonhematologic Malignancies

The purpose of this study is to evaluate the safety, pharmacokinetics, pharmacodynamics and maximum tolerated dose of TAK-733 in patients with advanced, nonhematologic tumors. The expansion stage of the study will evaluate evidence of antitumor activity of TAK-733 in patients with advanced metastatic melanoma.

Study Overview

• Status: Completed
• Conditions: Advanced Metastatic Melanoma; Advanced Non-hematologic Malignancies
• Intervention / Treatment: Drug: TAK-733

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detriot, Michigan, United States, 48201
      • Wayne State University Karmanos Cancer Institute
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria to be enrolled in the study:

• 18 years or older.
• Have one of the following diagnoses: a nonhematologic malignancy for which standard, curative, or life-prolonging treatment does not exist or is no longer effective; OR have stage 3 or stage 4 unresectable melanoma not priorly treated with either MEK or BRAF inhibitor therapy.
• Melanoma patients should have the V600E BRAF mutation status of their tumor documented, if available, and tumor tissue must be provided for confirmatory genotyping by a central laboratory.
• Have a radiographically or clinically evaluable tumor.
• Have suitable venous access for the conduct of blood sampling.
• Provide voluntary written consent, which can be withdrawn by the patient at any time.
• Female patients who: are post-menopausal for at least 1 year before screening; OR are surgically sterile; OR if they are of childbearing potential agree to practice two effective methods of birth control from the time of signing the informed consent form through 30 days after the last dose of the study drug, or agree to completely abstain from heterosexual intercourse.
• Male patients, even if surgically sterilized, must agree to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of the study drug; OR agree to completely abstain from heterosexual intercourse.

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

• Female patients who are lactating or have a positive serum pregnancy test during the Screening period.
• Antineoplastic therapy or radiotherapy within 21 days; or nitrosoureas of mitomycin C within 42 days
• Prior biologic or immunotherapy ≤ 4 weeks prior to enrollment.
• Grade 2 or greater unresolved toxicity (except alopecia) from previous anticancer therapy.
• Major surgery within 14 days of the first dose of the study drug.
• An active infection requiring systemic therapy; or other severe infection.
• Symptomatic brain metastases.
• Inability to meet specific laboratory test standards during the Screening period as specified in the study protocol.
• Human Immunodeficiency (HIV) positive.
• Hepatitis B surface antigen positive or active hepatitis C infection.
• Serious medical or psychiatric illness likely to interfere with the study.
• Uncontrolled cardiovascular condition.
• Abnormalities on 12-lead ECG performed within 28 days before the start of the study drug that are considered to be clinically significant or rate corrected QT interval > 470 milliseconds.
• Melanoma patients will be excluded if they have had a diagnosis with or treatment for another malignancy within 2 years of the first dose of the study drug, or have been previously diagnosed with another malignancy with any evidence of residual disease.
• Treatment with any investigational product within 28 days before the first dose of the study drug.
• A history of an ongoing or newly diagnosed eye abnormality, such as retinal or corneal pathologies.
• Abnormal left ventricular ejection fraction (LVEF).
• Receiving therapeutic anticoagulation
• Treatment with any of the following strong CYP3A inhibitors or inducers within 14 days before the first dose of study drug: ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone, rifampin, rifapentine, or rifabutin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: TAK-733

Drug: TAK-733; The Initial Escalation Stage will enroll approximately 30 patients with advanced nonhematologic malignancies. TAK-733 will be administered orally in 28-day treatment cycles consisting of intermittent dosing with 21 days of continuous treatment, followed by a rest period of 7 days. The Expansion Stage will enroll approximately 30 patients with advanced metastatic melanoma. The recommended phase 2 dose determined in the Initial Escalation Stage of TAK-733 will be administered orally in 28-day treatment cycles consisting of intermittent dosing with 21 days of continuous treatment, followed by a rest period of 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety profile, dose-limiting toxicities, maximum tolerated dose and recommended phase 2 dose of TAK-733	12 months
Pharmacokinetic characterization of TAK-733	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Effect of food on the pharmacokinetics of TAK-733	12 months
Antitumor activity of TAK-733 in patients with advanced nonhematologic malignancies	12 months
Antitumor activity of TAK-733 in melanoma patients	12 months

Collaborators and Investigators

• Sponsor: Millennium Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: July 27, 2009
• First Submitted That Met QC Criteria: July 28, 2009
• First Posted (Estimate): July 29, 2009

Study Record Updates

• Last Update Posted (Estimate): July 2, 2013
• Last Update Submitted That Met QC Criteria: July 1, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Advanced nonhematologic malignancies; Advanced metastatic melanoma; BRAF gene
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Neoplasms; Melanoma
• Other Study ID Numbers: C20001