Study to Determine the Effect of Food on the Blood Levels of AZD9291 Following Oral Dosing of a Tablet Formulation in Patients With Non-Small Cell Lung Cancer

NCT02163733 | Completed Phase 1 Results

• 2 other identifiers: D5160C000092014-001556-37
• Study Type: interventional
• Target: 38
• Locations: 4 countries
• Sites: 13

Brief Summary

This is a 2-part study in patients with epidermal growth factor receptor mutation positive (EGFRm+) non-small cell lung cancer (NSCLC) whose disease has progressed on treatment with an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI): Part A will determine the effect of food on the pharmacokinetics (PK) of AZD9291; Part B will allow patients further access to AZD9291 and will provide for additional safety data collection. Part A is a randomised, open-label, 2 treatment period crossover study in which patients will each receive a single oral dose of AZD9291 (1 x 80 mg tablet) at breakfast time (approximately 0800) in each of 2 treatment periods (once immediately following a high fat meal \[fed\], and once in the fasted state \[fasted\]), with a washout period of 9 days between doses. Approximately 38 patients are planned to be enrolled and dosed; at least 30 evaluable patients will be required to complete Part A (ie, the last PK sample in Treatment Period 2 \[TP 2\] has been collected). Additional patients may be enrolled to allow for at least 30 evaluable patients

Conditions

Advanced Non Small Cell Lung Cancer; Advanced (Inoperable) Non Small Cell Lung Cancer

Keywords

oncology, cancer, non small cell lung cancer, anticancer drug, pharmacokinetics, AZD9291, EGFR sensitivity mutation, food effect

Outcome Measures

Primary Outcomes (2)

• AUC(0-72) of AZD9291

  Pharmacokinetics of AZD9291 by assessment of area under the plasma concentration time curve from zero to 72 hours.

  Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 and 72 hours post AZD9291 dose in Part A.

• Cmax of AZD9291

  Pharmacokinetics of AZD9291 by assessment of maximum plasma AZD9291 concentration.

  Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.

Secondary Outcomes (13)

• AUC of AZD9291

  Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.

• AUC(0-t) of AZD9291

  Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.

• AUC(0-120) of AZD9291

  Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 120 hours post AZD9291 dose in Part A.

• Tmax of AZD9291

  Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.

• t1/2 of AZD9291

  Blood samples collected on Day 1 and Day 10 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 120, 168, and 216 hours post AZD9291 dose in Part A.

Study Arms (2)

Fasted

OTHER

AZD9291 tablets following a period of fasting

Drug: AZD9291 tablets; Procedure: Pharmacokinetic sampling - AZD9291; Other: Dietary Fasted; Procedure: Pharmacokinetic sampling - AZ5140 and AZ7550

High-fat meal

OTHER

AZD9291 tablets following a high-fat meal.

Drug: AZD9291 tablets; Procedure: Pharmacokinetic sampling - AZD9291; Other: Dietary High Fat; Procedure: Pharmacokinetic sampling - AZ5140 and AZ7550

Interventions

AZD9291 tablets DRUG

AZD9291 tablets: Part A 80mg od, days 1 and 10 only. Part B 80mg od for 12 months.

Fasted; High-fat meal

Pharmacokinetic sampling - AZD9291 PROCEDURE

Blood samples taken pre and post dosing of AZD9291 following either a period of fasting or consumption of a meal.

Fasted; High-fat meal

Dietary Fasted OTHER

Fasted from 10 hours prior to dosing with 80mg AZD9291 tablet and 4 hours after dosing

Fasted

Dietary High Fat OTHER

Allocated breakfast prior to dosing with 80mg AZD9291 tablet

High-fat meal

Pharmacokinetic sampling - AZ5140 and AZ7550 PROCEDURE

Blood samples taken pre and post dosing of AZD9291 following either a period of fasting or consumption of a meal.

Fasted; High-fat meal

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Participation in another clinical study with an IP during the last 14 days (or a longer period depending on the defined characteristics of the agents used).
• Treatment with any of the following: Treatment with an EGFR TKI w/in 8 days or approximately 5x half-life, whichever is the longer, of the first dose of study treatment; Any cytotoxic chemotherapy, investigational agents or other anticancer drugs w/in 14 days of the first dose of study treatment; Major surgery (excluding placement of vascular access) within 4 weeks of the first dose; Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation which must be completed within 4 weeks of the first dose of study treatment; Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inhibitors of CYP2C8 and of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on CYP3A4, CYP2C8, and/ or CYP1A2.
• Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of the IP until the end of Part A.
• Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum therapy related neuropathy.
• Patients unable to fast for up to 14 hours.
• Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to start of study treatment.
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the Investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus. Screening for chronic conditions is not required.
• Patients with type I diabetes.
• Patients unable to swallow orally administered medication or patients with gastrointestinal disorders or significant gastrointestinal resection likely to interfere with the absorption of AZD9291.
• Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
• Women who are breastfeeding.
• Patients with a known hypersensitivity to AZD9291
• Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: Absolute neutrophil count (ANC) \<1.5 x 109/L; Platelet count \<100 x 109/L; Haemoglobin \<90 g/L; ALT \>2.5 x the institutional ULN if no demonstrable liver metastases or \>5 x institutional ULN in the presence of liver metastases; AST \>2.5 x institutional ULN if no demonstrable liver metastases or \>5 x institutional ULN in the presence of liver metastases; Total bilirubin \>1.5 x institutional ULN if no liver metastases or \>3 x institutional ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases; Creatinine \>1.5 x institutional ULN concurrent with creatinine clearance \<50 mL/min (measured or calculated by Cockcroft-Gault formula); confirmation of creatinine clearance is only required when creatinine is \>1.5 x institutional ULN.
• Any of the following cardiac criteria: Mean resting corrected QT interval corrected for heart rate using Fridericia's correction factor (QTcF) \>470 msec obtained from 3 ECGs; Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, third degree heart block, second degree heart block, PR interval \>250 msec; Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval.
• For optional genetic research: Previous allogenic bone marrow transplant or non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (13)

Research Site

Dijon, 21079, France

Location

Research Site

Lyon, 69373, France

Location

Research Site

Saint-Herblain, 44805, France

Location

Research Site

Seoul, 03722, South Korea

Location

Research Site

Seoul, 05505, South Korea

Location

Research Site

Madrid, 28040, Spain

Location

Research Site

Madrid, 28041, Spain

Location

Research Site

Madrid, 28050, Spain

Location

Research Site

Seville, 41013, Spain

Location

Research Site

London, SE1 9RT, United Kingdom

Location

Research Site

Manchester, M20 4BX, United Kingdom

Location

Research Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Research Site

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• Vishwanathan K, Dickinson PA, Bui K, Cassier PA, Greystoke A, Lisbon E, Moreno V, So K, Thomas K, Weilert D, Yap TA, Plummer R. The Effect of Food or Omeprazole on the Pharmacokinetics of Osimertinib in Patients With Non-Small-Cell Lung Cancer and in Healthy Volunteers. J Clin Pharmacol. 2018 Apr;58(4):474-484. doi: 10.1002/jcph.1035. Epub 2017 Nov 26.

  PMID: 29178442 DERIVED

Related Links

• Study9\_Redacted
• CSR Synopsis Redacted

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

At end of Part B, the CAP allowed patients to continue receiving AZD9291 if still deriving clinical benefit. No clinical data was databased during the CAP; thus AE data is presented to end of Part B only.

Results Point of Contact

• Title: Dr Karen So
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Serban Ghiorghiu, MSD

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2014
• First Posted: June 16, 2014
• Study Start: November 14, 2014
• Primary Completion: March 24, 2015
• Study Completion: January 24, 2023
• Last Updated: January 22, 2024
• Results First Posted: April 5, 2016

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

KR (2); FR (3); ES (4); GB (4)