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)

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01605916

Enrollment

Registered

2012-05-25

Start date

2012-06-30

Completion date

2015-05-31

Last updated

2016-10-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

Cancer,, Tumour,, Metastatic,, Lung cancer,, Non-Small Cell Lung Cancer

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.

Interventions

DRUGAZD6244

Tablet Oral bid

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

20 Years to 130 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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
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
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
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
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
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
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

Measure	Time frame	Description
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
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
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

Countries

Japan

Participant flow

Recruitment details

First patient enrolled on 01 June 2012. Last subject last visit on 30 March 2015.

Pre-assignment details

Out of 33 enrolled subjects, 25 subjects were assigned to selumetinib (AZD6244, ARRY-142886), and 8 subjects were not assigned. The reasons of no assignment were 'Screen failure' (7 subjects) and 'Withdrawal by subject' (1 subject).

Participants by arm

Arm	Count
Combination Therapy Cohort 1 Selumetinib 75 mg + Doce Combination therapy of Selumetinib 75 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer	4
Combination Therapy Cohort 2 Selumetinib 25 mg + Doce Combination therapy of Selumetinib 25 mg twice a day with docetaxel 60 mg/m2 every 21 days for Japanese patients with locally advanced or metastatic non-small cell lung cancer	4
Monotherapy Cohort 1 Selumetinib 25 mg Monotherapy of Selumetinib 25 mg twice a day for Japanese patients with advanced solid malignancies	4
Monotherapy Cohort 2 Selumetinib 50 mg Monotherapy of Selumetinib 50 mg twice a day for Japanese patients with advanced solid malignancies	6
Monotherapy Cohort 3 Selumetinib 75 mg Monotherapy of Selumetinib 75 mg twice a day for Japanese patients with advanced solid malignancies	7
Total	25

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Adverse Event	1	0	0	1	0
Overall Study	Lack of Efficacy	2	3	3	5	4
Overall Study	Withdrawal by Subject	1	1	0	0	2

Baseline characteristics

Characteristic	Combination Therapy Cohort 1 Selumetinib 75 mg + Doce	Combination Therapy Cohort 2 Selumetinib 25 mg + Doce	Monotherapy Cohort 1 Selumetinib 25 mg	Monotherapy Cohort 2 Selumetinib 50 mg	Monotherapy Cohort 3 Selumetinib 75 mg	Total
Age, Continuous	55.5 Years STANDARD_DEVIATION 17.33	58.8 Years STANDARD_DEVIATION 8.5	60.0 Years STANDARD_DEVIATION 12.36	60.0 Years STANDARD_DEVIATION 11.75	66.7 Years STANDARD_DEVIATION 12.22	61.0 Years STANDARD_DEVIATION 12.15
Sex: Female, Male Female	1 Participants	1 Participants	2 Participants	1 Participants	4 Participants	9 Participants
Sex: Female, Male Male	3 Participants	3 Participants	2 Participants	5 Participants	3 Participants	16 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	4 / 4	4 / 4	4 / 4	6 / 6	7 / 7
serious Total, serious adverse events	0 / 4	0 / 4	1 / 4	1 / 6	2 / 7

Outcome results

Primary

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

Time frame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose