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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01605916
First received: May 21, 2012
Last updated: June 3, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Neoplasms,
Metastatic Cancer,
Non-Small Cell Lung Cancer
Advanced Solid Malignancies
Drug: AZD6244
Drug: Docetaxel
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 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)

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter (Cmax: maximum plasma concentration) of Selumetinib following single oral dose of Selumetinib

  • 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 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of Selumetinib following single oral dose of Selumetinib

  • AUC(0-12) 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 ] [ Designated as safety issue: No ]
    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

  • 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 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter (Cmax: maximum plasma concentration) of N-desmethyl Selumetinib following single oral dose of Selumetinib

  • 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 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of N-desmethyl Selumetinib following single oral dose of Selumetinib

  • AUC(0-12) 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 ] [ Designated as safety issue: No ]
    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

  • 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 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter (Cmax: maximum plasma concentration) of Selumetinib during oral twice daily dose of Selumetinib

  • 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 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of Selumetinib during oral twice daily dose of Selumetinib

  • 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 ] [ Designated as safety issue: No ]
    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

  • 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 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter (Cmax: maximum plasma concentration) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib

  • 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 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib

  • 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 ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter (Cmax: maximum plasma concentration) of docetaxel following intravenous infusion of docetaxel 60 mg/m2 in combination with Selumetinib

  • 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 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of docetaxel following intravenous infusion of docetaxel 60 mg/m2 in combination with Selumetinib

  • 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 ] [ Designated as safety issue: No ]
    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


Enrollment: 33
Study Start Date: June 2012
Study Completion Date: May 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AZD6244 with or without Docetaxel
AZD6244 with or without Docetaxel
Drug: AZD6244
Tablet Oral bid
Drug: Docetaxel
IV once every 21 days
Other Name: Taxotere

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.

  Eligibility

Ages Eligible for Study:   20 Years to 130 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01605916

Locations
Japan
Research Site
Fukuoka-shi, Japan
Research Site
Kashiwa-shi, Japan
Research Site
Nagoya-shi, Japan
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Ian Smith, Medical Science Director AstraZeneca
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
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01605916     History of Changes
Other Study ID Numbers: D1532C00067 
Study First Received: May 21, 2012
Results First Received: April 6, 2016
Last Updated: June 3, 2016
Health Authority: Japan: Ministry of Health, Labor and Welfare
Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by AstraZeneca:
Cancer,
Tumour,
Metastatic,
Lung cancer,
Non-Small Cell Lung Cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms
Neoplasm Metastasis
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neoplastic Processes
Pathologic Processes
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 27, 2016