Clinical trial NCT01802632: AZD9291 First Time In Patients Ascending Dose Study
Official title: Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of AZD9291 in Patients With Advanced Non Small Cell Lung Cancer Who Progressed on Prior Therapy With an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Non Small Cell Lung Cancer
Advanced (Inoperable) Non Small Cell Lung Cancer
Keywords: Oncology,
Non Small Cell Lung Cancer,
Metastatic,
EGFR sensitivity mutation,
T790M resistance mutation
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-03-01
Enrollment: 603
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will treat patients with advanced NSCLC who have already received at least one course of specific anti-cancer treatment but the tumour has started to re-grow following that treatment. This is the first time this drug has ever been tested in patients, and so it will help to understand what type of side effects may occur with the drug treatment, it will measure the levels of drug in the body, it will also measure the anti-cancer activity. By using these pieces of information together the best dose of this drug to use in further clinical trials will be selected.

Detailed description: A Phase I/II, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumour Activity of Ascending Doses of AZD9291 in Patients with Advanced Non Small Cell Lung Cancer who have Progressed Following Prior Therapy with an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent (AURA)

Eligibility criteria: Inclusion Criteria:

* Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
* Aged at least 18 years. Patients from Japan aged at least 20 years.
* Histological or cytological confirmation diagnosis of Non Small Cell Lung Cancer (NSCLC).
* Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI e.g. gefitinib or erlotinib (with the exception of 1st line expansion cohort). In addition other lines of therapy may have been given. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study.
* Patients (with the exception of 1st line expansion cohort) must fulfil one of the following:

  * Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q) OR
  * Must have experienced clinical benefit from EGFR TKI, according to the Jackman criteria (Jackman et al 2010) followed by systemic objective progression (RECIST or WHO) while on continuous treatment with EGFR TKI.
* Previous treatment with a single-agent EGFR TKI (e.g. gefitinib or erlotinib).
* Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing or evidence of non-child bearing potential.
* Male patients should be willing to use barrier contraception.
* For 1st Line expansion cohort ONLY, confirmation that the tumour is EGFRm+ve and have had no prior therapy for their advanced disease (for 1st line patients biopsy will be at time of diagnosis of advanced disease).
* For dose expansion and extension cohorts, patients must also have confirmation of tumour T790M mutation status (confirmed positive or negative) from a biopsy sample taken after disease progression on the most recent treatment regimen (irrespective of whether this is EGFR TKI or chemotherapy).

Prior to entry a result from the central analysis of the patient's T790M mutation status must be obtained.

- World Health Organisation (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.

Exclusion Criteria:

* Treatment with an EGFR TKI (erlotinib or gefitinib) within 8 days (approximately 5x half-life) of the first dose of study treatment.
* Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
* AZD9291 in the present study (ie, dosing with AZD9291 previously initiated in this study).
* Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection.
* Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease.

Primary outcomes:
measure: Objective Response Rate (ORR) for Dose Expansion Population
timeFrame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis)
measure: Best Objective Response (BOR) for Dose Escalation Population
timeFrame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 25 months (at time of analysis)
measure: Objective Response Rate (ORR) for Extension Population
timeFrame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 12 months (at the time of analysis)
Secondary outcomes:
measure: Duration of Response (DoR) for Dose Expansion Population
timeFrame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis)
measure: Progression-Free Survival (PFS) for Dose Expansion Population
timeFrame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis)
measure: Best Objective Response (BOR) for 80mg AZD9291 Extension Population
timeFrame: RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 12 months (at the time of analysis)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Heidelberg
country: Australia
facility: Research Site
city: Kogarah
country: Australia
facility: Research Site
city: Nedlands
country: Australia
facility: Research Site
city: Pierre Benite CEDEX
country: France
facility: Research Site
city: Saint Herblain Cedex
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Würzburg
country: Germany
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Orbassano
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Chiba-shi
country: Japan
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Fukuoka
country: Japan
facility: Research Site
city: Habikino-shi
country: Japan
facility: Research Site
city: Hirakata-shi
country: Japan
facility: Research Site
city: Hiroshima-shi
country: Japan
facility: Research Site
city: Kanazawa
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Matsuyama-shi
country: Japan
facility: Research Site
city: Okayama-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Takatsuki-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Yuri Rukazenkov
role: STUDY_DIRECTOR
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citation: Dearden S, Brown H, Jenkins S, Thress KS, Cantarini M, Cole R, Ranson M, Janne PA. EGFR T790M mutation testing within the osimertinib AURA Phase I study. Lung Cancer. 2017 Jul;109:9-13. doi: 10.1016/j.lungcan.2017.04.011. Epub 2017 Apr 19.
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