Study to Assess the Effect of Itraconazole (a CYP3A4 Inhibitor) on the Pharmacokinetics of AZD9291, in Patients With EGFR Positive Non-small Cell Lung Cancer. Patients Will be Chosen From Those Who Have Already Been Prescribed an EGFR TKI Medicine (Such as Iressa or Tarceva)

Phase 1

Completed

• Conditions: Advanced Non Small Cell Lung Cancer; Advanced (Inoperable) Non Small Cell Lung Cancer
• Interventions: Procedure: Pharmacokinetic sampling; Drug: AZD9291; Drug: Itraconazole

• Registration Number: NCT02157883
• Lead Sponsor: AstraZeneca

Brief Summary

This is a 2 part study in patients with EGFRm+ non small cell lung cancer (NSCLC), whose disease has progressed on an EGFRm TKI, who are refractory or resistant to standard therapy. Part A will assess the effect of multiple oral doses of itraconazole on the single dose pharmacokinetic (PK) parameters of AZD9291. On completion of Part A, patients may continue to take AZD9291 tablets (Part B) following the collection of the 216 hour sample on Day 19 if they and the Investigator deem it appropriate, until such time as their disease progresses, the Investigator believes they are no longer deriving clinical benefit, or they stop taking AZD9291 for any other reason

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-06-05
• Study First Submitted QC: 2014-06-05
• Study First Posted: 2014-06-06
• Study Start: 2014-11-06
• Primary Completion: 2015-04-03
• Results First Submitted: 2016-03-15
• Results First Submitted QC: 2016-03-15
• Results First Posted: 2016-04-14
• Study Completion: 2023-05-17
• Status Verified: 2024-02
• Last Update Submitted: 2024-03-12
• Last Update Posted: 2024-03-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
AZD9291 alone, AZD9291+itraconozole	Pharmacokinetic sampling	Sequential treatments of AZD9291 alone followed by AZD9291+itraconazole, with a washout period in between.
AZD9291 alone, AZD9291+itraconozole	AZD9291	Sequential treatments of AZD9291 alone followed by AZD9291+itraconazole, with a washout period in between.
AZD9291 alone, AZD9291+itraconozole	Itraconazole	Sequential treatments of AZD9291 alone followed by AZD9291+itraconazole, with a washout period in between.

Primary Outcome Measures

Name	Time	Method
Cmax of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZD9291 by assessment of maximum plasma AZD9291 concentration
AUC of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to infinity

Secondary Outcome Measures

Name	Time	Method
AUC(0-120) of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to 120 hours
Tmax of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZD9291 by assessment of time to Cmax
AUC of AZ5104	Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZ5104 (metabolite to AZD9291) by assessment of area under the plasma concentration time curve from zero to infinity
AUC of AZ7550	Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZ7550 (metabolite to AZD9291) by assessment of area under the plasma concentration time curve from zero to infinity
Cmax of AZ5104	Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZ5104 (metabolite to AZD9291) by assessment of maximum plasma AZ5104 concentration
t1/2 of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZD9291 by assessment of the terminal half-life
Vz/F of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.	Rate and extent of absorption of AZD9291 by assessment of the apprarent volume of distribution
Cmax of AZ7550	Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZ7550 (metabolite to AZD9291) by assessment of maximum plasma AZ7550 concentration
AUC(0-t) of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.	Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration curve from time zero to last quantifiable dose
CL/F of AZD9291	Blood samples collected on Day 1 and Day 10 at pre-dose, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, and 216 hours post AZD9291 dose in Part A.	Rate and extent of absorption of AZD9291 by assessment of apparent clearance following oral administration

Trial Locations

Locations (1)

Research Site; 🇬🇧 Manchester, United Kingdom