Clinical trial NCT01605916: Investigate the Safety and Tolerability of AZD6244 Monotherapy or + Docetaxel in Japanese Patients With Advanced Solid Malignancies or Non-Small Cell Lung Cancer
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms,
Metastatic Cancer,
Non-Small Cell Lung Cancer
Advanced Solid Malignancies
Keywords: Cancer,
Tumour,
Metastatic,
Lung cancer,
Non-Small Cell Lung Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2012-05-25
Enrollment: 33
Sex: ALL
Minimum age (years): 20
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Cmax of Selumetinib After Single Dose
timeFrame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
measure: Tmax of Selumetinib After Single Dose
timeFrame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
measure: AUC(0-12) of Selumetinib After Single Dose
timeFrame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
measure: Cmax of N-desmethyl Selumetinib After Single Dose
timeFrame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
measure: Tmax of N-desmethyl Selumetinib After Single Dose
timeFrame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72 hours post-dose
measure: AUC(0-12) of N-desmethyl Selumetinib After Single Dose
timeFrame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
measure: Cmax of Selumetinib During Oral Twice Daily Dose of Selumetinib
timeFrame: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
measure: Tmax of Selumetinib During Oral Twice Daily Dose of Selumetinib
timeFrame: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
measure: AUC(0-12) of Selumetinib During Oral Twice Daily Dose of Selumetinib
timeFrame: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
measure: Cmax of N-desmethyl Selumetinib During Oral Twice Daily Dose of Selumetinib
timeFrame: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
measure: Tmax of N-desmethyl Selumetinib During Oral Twice Daily Dose of Selumetinib
timeFrame: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
measure: AUC(0-12) of N-desmethyl Selumetinib During Oral Twice Daily Dose of Selumetinib
timeFrame: Day 8: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Secondary outcomes:
measure: Cmax of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2
timeFrame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
measure: Tmax of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2
timeFrame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
measure: AUC(0-12) of Docetaxel Following Intravenous Infusion of Docetaxel 60 mg/m2
timeFrame: Day 1: 0, 0.5, 1, 1.5, 2, 4, 8, 12 hours post-dose
Other outcomes:
Locations:
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Kashiwa-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Ian Smith, Medical Science Director
role: STUDY_DIRECTOR
affiliation: National Cancer Centre East
name: Yuichiro Ohe, Medical Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: National Hospital Organisation Nagoya Medical Centre
name: Hideo Saka, Medical Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: National Hospital Organization Kyushu Cancer Center
name: Takashi Seto, Medical Doctor
role: PRINCIPAL_INVESTIGATOR
References: