Overview

This trial is active, not recruiting.

Condition non-small cell lung cancer
Treatment azd9291
Phase phase 2
Target EGFR
Sponsor AstraZeneca
Start date June 2015
End date March 2016
Trial size 319 participants
Trial identifier NCT02442349, D5160C00017

Summary

A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of AZD9291 in Asia Pacific Patients with Locally Advanced/Metastatic Non-Small Cell Lung Cancer whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and whose Tumours harbour a T790M mutation within the Epidermal Growth Factor Receptor Gene

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Once daily tablet 80 mg
azd9291
Once daily tablet 80 mg

Primary Outcomes

Measure
ORR according to RECIST 1.1
time frame: At baseline and every 6 weeks from time of first dose until objective disease progression, for an average of approximately 12 months.

Secondary Outcomes

Measure
PFS according to RECIST 1.1
time frame: At baseline and every 6 weeks from time of first dose until objective disease progression, for an average of approximately 12 months.
Patient Reported Outcomes by EORTC QLQ-C30 questionnaire
time frame: Questionnaires completed at baseline, every 6 weeks relative to first dose, discontinuation and during the progression and survival follow-up periods for approximately 2 years.
Overall Survival (OS)
time frame: From first dose to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks up to approximately 60 months.
DoR according to RECIST 1.1
time frame: At baseline and every 6 weeks from time first dose until date of progression, for an average of approximately 12 months.
DCR according to RECIST 1.1
time frame: At baseline and every 6 weeks from time first dose until date of progression, for an average of approximately 12 months.
Tumour shrinkage according to RECIST 1.1
time frame: At baseline and every 6 weeks from time of first dose until date of progression, for an average of approximately 12 months.
Patient Reported Outcomes by EORTC QLQ LC13 questionnaire
time frame: Questionnaires completed at baseline, weekly for the first 3 weeks, then every 3 weeks (relative to first dose), discontinuation and during the progression and survival follow-up periods for approximately 2 years.
Safety and tolerability profile of AZD9291.
time frame: Adverse events will be collected from baseline until 28 days after the last dose, expected average 12 months.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Aged at least 18 years. Patient from Asia Pacific will be enrolled only. - Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy. - Radiological documentation of disease progression on the last treatment administered prior to enrolling in the study: following 1st line EGFR TKI treatment but who have not received further treatment OR following prior therapy with an EGFR TKI and a platinum-based doublet chemotherapy. Patients may have also received additional lines of treatment. - Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). - Patients must have central confirmation of tumour T790M mutation positive status from a biopsy sample taken after confirmation of disease progression on the most recent treatment regimen. - World Health Organisation (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks. - At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline as ≥10mm in the longest diameter (except lymph nodes which must have short axis ≥15mm) with computerised tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements. - Females of child-bearing potential using contraception and must have a negative pregnancy test. Exclusion Criteria: - Treatment with an EGFR-TKI (eg, erlotinib, gefitinib, icotinib or afatinib) within 8 days or approximately 5x half-life of study entry; any cytotoxic chemotherapy, investigational agents or other anticancer drugs within 14 days of study entry; previous treatment with AZD9291 or a 3rd generation EGFR TKIs; Major surgery within 4 weeks of study entry; radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of study entry; currently receiving treatment with potent inhibitors or inducers of CYP3A4. - Any unresolved toxicities from prior therapy. - Unstable spinal cord compression or brain metastases. - Severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses or infection. - Refractory nausea and vomiting, chronic gastrointestinal diseases or bowel resection. - Cardiac disease. - 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. - Inadequate bone marrow reserve or organ function.

Additional Information

Official title A Phase II, Open Label, Single-arm Study to Assess the Safety and Efficacy of AZD9291 in Asia Pacific Patients With Locally Advanced/Metastatic Non-Small Cell Lung Cancer Whose Disease Has Progressed With Previous Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Whose Tumours Harbour a T790M Mutation Within the Epidermal Growth Factor Receptor Gene
Description This is a phase II, open label, single arm study assessing the safety and efficacy of AZD9291 (80 mg, orally, once daily) in Asia Pacific patients with a confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) sensitising mutation positive (ie, G719X, exon 19 deletion, L858R, L861Q) and T790M mutation positive (hereafter referred to as EGFRm+ and T790M+) un-resectable, locally advanced or metastatic NSCLC (Stage IIIB-IV), who have progressed on an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor(EGFR-TKI), either as first line treatment or following one line of EGFR-TKI and one line of platinum containing doublet chemotherapy. Patients must agree to provide a biopsy for central confirmation of T790M mutation status following confirmed disease progression on the most recent treatment regimen. The primary objective of the study is to assess the efficacy of AZD9291 by assessment of Objective Response Rate according to RECIST 1.1 by an Independent Central Review.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by AstraZeneca.