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

Phase 1

Completed

• Conditions: Metastatic Cancer,; Non-Small Cell Lung Cancer; Neoplasms,; Advanced Solid Malignancies
• Interventions: Drug: AZD6244

• Registration Number: NCT01605916
• Lead Sponsor: AstraZeneca

Brief Summary

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.

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 Timeline

• Study First Submitted: 2012-05-21
• Study First Submitted QC: 2012-05-24
• Study First Posted: 2012-05-25
• Study Start: 2012-06
• Primary Completion: 2015-04
• Study Completion: 2015-05
• Results First Submitted: 2016-04-06
• Results First Submitted QC: 2016-06-03
• Results First Posted: 2016-07-14
• Status Verified: 2016-09
• Last Update Submitted: 2016-09-08
• Last Update Posted: 2016-10-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 33

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Selumetinib (AZD6244) 25 mg	AZD6244	monotherapy
Selumetinib (AZD6244) 50 mg	AZD6244	monotherapy
Selumetinib (AZD6244) 25 mg + Doce	AZD6244	combination
Selumetinib (AZD6244) 75 mg	AZD6244	monotherapy
Selumetinib (AZD6244) 75 mg + Doce	AZD6244	Combination

Primary Outcome Measures

Name	Time	Method
Cmax of Selumetinib During Oral Twice Daily Dose of Selumetinib	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
AUC(0-12) 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	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
Cmax 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	Pharmacokinetic parameter (Cmax: maximum plasma concentration) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib
Cmax of Selumetinib After Single Dose	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
Tmax of Selumetinib After Single Dose	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
AUC(0-12) of Selumetinib After Single Dose	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
Cmax of N-desmethyl Selumetinib After Single Dose	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
Tmax of N-desmethyl Selumetinib After Single Dose	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
AUC(0-12) of N-desmethyl Selumetinib After Single Dose	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
AUC(0-12) of Selumetinib During Oral Twice Daily Dose of Selumetinib	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
Tmax 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	Pharmacokinetic parameter (tmax: time to reach the maximum plasma concentration) of N-desmethyl Selumetinib during oral twice daily dose of Selumetinib
Tmax of Selumetinib During Oral Twice Daily Dose of Selumetinib	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

Secondary Outcome Measures

Name	Time	Method
Cmax of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2	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
AUC(0-12) of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2	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
Tmax of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2	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

Trial Locations

Locations (1)

Research Site; 🇯🇵 Nagoya-shi, Japan