Investigate the Safety and Tolerability of AZD6244 Monotherapy or + Docetaxel in Japanese Patients With Advanced Solid Malignancies or Non-Small Cell Lung Cancer

September 8, 2016 updated by: AstraZeneca

A Phase I, Open-Label Study to Investigate the Safety and Tolerability of AZD6244 (Selumetinib) When Given as a Monotherapy in Japanese Patients With Advanced Solid Malignancies, and When Given in Combination With Docetaxel as 2nd Line Therapy in Japanese Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV)

The objective of this study will be to investigate the safety and tolerability of AZD6244 given monotherapy or in combination with docetaxel as 2nd line therapy in Japanese patients with Advanced Solid Malignancies or Locally Advanced or Metastatic Non-Small Cell Lung Cancer. In addition, the pharmacokinetic profile of AZD6244 will be investigated. Following the combination regimen dose escalation phase (Part A) of the study additional patients may be enrolled to a dose expansion phase (Part B) to refine further the safety, tolerability, pharmacokinetics and biological activity of the combination in this patient population.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The objective of the combination therapy part of this study will be to investigate the safety and tolerability of AZD6244 given in combination with docetaxel as 2nd line therapy in Japanese patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV). In addition, the pharmacokinetic profile of AZD6244 and docetaxel will be investigated.

The objective of the monotherapy part of this study will be to investigate the safety and tolerability of AZD6244 given as a monotherapy in Japanese patients with advanced solid malignancies. In addition, the pharmacokinetic profile of monotherapy AZD6244 will be investigated.

Study Type

Interventional

Enrollment (Actual)

33

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Fukuoka-shi, Japan
        • Research Site
      • Kashiwa-shi, Japan
        • Research Site
      • Nagoya-shi, Japan
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 130 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients diagnosed with lung cancer who have not responded to prior therapy or have become worse.
  • Patients who have overall good general conditions.
  • Patients who have at least one lesion that can be accurately assessed by imaging.
  • Patients who have appropriate renal conditions confirmed by test results for taking part in the study.
  • Evidence of non-childbearing status for women of childbearing potential, or postmenopausal status.

Exclusion Criteria:

  • Patients with brain metastases or spinal cord compression.
  • Patients with significant abnormal ECG findings.
  • Patients with evidence of severe or uncontrolled systemic disease.
  • The main organ functional test values for bone marrow, kidney, and liver, etc., do not meet the standards.
  • Patients with known hypersensitivity to docetaxel or products containing polysorbate 80.

Only for monotherapy cohort eligibility criteria Patients with advanced solid malignancies refractory to standard treatment or for which no standard therapy exists irrespective of the stage and previous treatment.

Patients with histologically or cytologically confirmed advanced solid malignancies.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Selumetinib (AZD6244) 25 mg
monotherapy
Drug: AZD6244
Tablet Oral bid
Other Names:
  • Selumetinib (AZD6244)
Experimental: Selumetinib (AZD6244) 50 mg
monotherapy
Drug: AZD6244
Tablet Oral bid
Other Names:
  • Selumetinib (AZD6244)
Experimental: Selumetinib (AZD6244) 75 mg
monotherapy
Drug: AZD6244
Tablet Oral bid
Other Names:
  • Selumetinib (AZD6244)
Experimental: Selumetinib (AZD6244) 75 mg + Doce
Combination
Drug: AZD6244
Tablet Oral bid
Other Names:
  • Selumetinib (AZD6244)
Experimental: Selumetinib (AZD6244) 25 mg + Doce
combination
Drug: AZD6244
Tablet Oral bid
Other Names:
  • Selumetinib (AZD6244)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cmax of Selumetinib After Single Dose
Time Frame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
Pharmacokinetic parameter (Cmax: maximum plasma concentration) of Selumetinib following single oral dose of Selumetinib
Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
Tmax of Selumetinib After Single Dose
Time Frame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of Selumetinib following single oral dose of Selumetinib
Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
AUC(0-12) of Selumetinib After Single Dose
Time Frame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dosey) of Selumetinib following single oral dose of Selumetinib
Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Cmax of N-desmethyl Selumetinib After Single Dose
Time Frame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
Pharmacokinetic parameter (Cmax: maximum plasma concentration) of N-desmethyl Selumetinib following single oral dose of Selumetinib
Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
Tmax of N-desmethyl Selumetinib After Single Dose
Time Frame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of N-desmethyl Selumetinib following single oral dose of Selumetinib
Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
AUC(0-12) of N-desmethyl Selumetinib After Single Dose
Time Frame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dose) of N-desmethyl Selumetinib following single oral dose of Selumetinib
Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Cmax of Selumetinib During Oral Twice Daily Dose of Selumetinib
Time Frame: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (Cmax: maximum plasma concentration) of Selumetinib during oral twice daily dose of Selumetinib
Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Tmax of Selumetinib During Oral Twice Daily Dose of Selumetinib
Time Frame: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of Selumetinib during oral twice daily dose of Selumetinib
Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
AUC(0-12) of Selumetinib During Oral Twice Daily Dose of Selumetinib
Time Frame: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dose) of Selumetinib during oral twice daily dose of Selumetinib
Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Cmax of N-desmethyl Selumetinib During Oral Twice Daily Dose of Selumetinib
Time Frame: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (Cmax: maximum plasma concentration) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib
Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Tmax of N-desmethyl Selumetinib During Oral Twice Daily Dose of Selumetinib
Time Frame: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib
Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
AUC(0-12) of N-desmethyl Selumetinib During Oral Twice Daily Dose of Selumetinib
Time Frame: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dose) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib
Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cmax of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2
Time Frame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (Cmax: maximum plasma concentration) of docetaxel following intravenous infusion of docetaxel 60 mg/m2 in combination with Selumetinib
Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Tmax of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2
Time Frame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of docetaxel following intravenous infusion of docetaxel 60 mg/m2 in combination with Selumetinib
Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
AUC(0-12) of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2
Time Frame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Pharmacokinetic parameter (AUC(0-12): area under the plasma concentration-time curve from zero to 12 hours post-dose) of docetaxel following intravenous infusion of docetaxel 60 mg/m2 in combination with Selumetinib
Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Investigators

  • Principal Investigator: Yuichiro Ohe, Medical Doctor, National Cancer Centre East
  • Principal Investigator: Hideo Saka, Medical Doctor, National Hospital Organisation Nagoya Medical Centre
  • Principal Investigator: Takashi Seto, Medical Doctor, National Hospital Organization Kyushu Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (Actual)

April 1, 2015

Study Completion (Actual)

May 1, 2015

Study Registration Dates

First Submitted

May 21, 2012

First Submitted That Met QC Criteria

May 24, 2012

First Posted (Estimate)

May 25, 2012

Study Record Updates

Last Update Posted (Estimate)

October 21, 2016

Last Update Submitted That Met QC Criteria

September 8, 2016

Last Verified

September 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D1532C00067

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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