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

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: Non-Small Cell Lung Cancer; Advanced Solid Malignancies; Neoplasms,; Metastatic Cancer,
• Intervention / Treatment: Drug: AZD6244

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

Study Locations

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

Participation Criteria

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

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

5

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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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

• 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

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: Non-Small Cell Lung Cancer; Cancer,; Lung cancer,; Metastatic,; Tumour,
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: D1532C00067