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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Neoplasms,, Metastatic Cancer,, Non-Small Cell Lung Cancer, Advanced Solid Malignancies

Intervention / Treatment
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* Drug: AZD6244


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selumetinib (AZD6244) 25 mg<br>monotherapy | Drug: AZD6244<br>* Tablet Oral bid<br>* Other names: Selumetinib (AZD6244);|
| Experimental: Selumetinib (AZD6244) 50 mg<br>monotherapy | Drug: AZD6244<br>* Tablet Oral bid<br>* Other names: Selumetinib (AZD6244);|
| Experimental: Selumetinib (AZD6244) 75 mg<br>monotherapy | Drug: AZD6244<br>* Tablet Oral bid<br>* Other names: Selumetinib (AZD6244);|
| Experimental: Selumetinib (AZD6244) 75 mg + Doce<br>Combination | Drug: AZD6244<br>* Tablet Oral bid<br>* Other names: Selumetinib (AZD6244);|
| Experimental: Selumetinib (AZD6244) 25 mg + Doce<br>combination | Drug: AZD6244<br>* Tablet Oral bid<br>* Other names: Selumetinib (AZD6244);|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer,, Tumour,, Metastatic,, Lung cancer,, Non-Small Cell Lung Cancer