AZD9291, an Irreversible EGFR-TKI, in Relapsed EGFR-mutated Non-small Cell Lung Cancer Patients Previously Treated With an EGFR-TKI, Coupled to Extensive Translational Studies

NCT02504346 | Unknown Phase 2

• 1 other identifier: 2015/10301
• Study Type: interventional
• Target: 200
• Locations: 5 countries
• Sites: 7

Brief Summary

Phase II, single-arm study to assess the safety and efficacy of AZD9291 (80 mg, orally, once daily) in second-line (or later) patients with EGFR mutation-positive, locally advanced or metastatic NSCLC, who have progressed following treatment with an approved epidermal growth factor tyrosine kinase inhibitor agent.

Conditions

Lung Cancer; Targeted Therapy

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Measured by RECIST 1.1

  12 weeks

Study Arms (1)

Treatment

EXPERIMENTAL

Non-randomized trial, all patients receive therapy - singel-arm

Drug: AZD9291

Interventions

AZD9291 DRUG

Treatment

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated, written informed consent.
• Age \> 18 years.
• Histologically or cytologically documented locally advanced or metastatic NSCLC not amenable to curative surgery or radiotherapy.
• Radiological disease progression following at least one prior EGFR TKI.
• Documented EGFR mutation known to be associated with EGFR TKI sensitivity (also including T790M).
• ECOG status 0-2 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 according to RECIST 1.1.
• Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
• Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
• Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels in the post-menopausal range for the institution
• Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
• Male subjects must be willing to use barrier contraception.

You may not qualify if:

• \. Treatment with an EGFR-TKI within 8 days or approximately 5x half-life, whichever is the longer, of the first dose of study treatment.
• \. Treatment with cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days or approximately 5x half-life, whichever is the longer, of the first dose of study treatment.
• \. Spinal cord compression or brain metastases unless asymptomatic and on stable steroid dosage for at least 2 weeks prior to start of study treatment.
• \. Any evidence of severe or uncontrolled systemic diseases which in the investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
• \. Gastrointestinal conditions incompatible with swallowing or precluding absorption of AZD9291.
• \. Exclude based on any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc using Fredericia's formula) \> 470 msec
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval 12. Current or previous significant interstitial lung disease or radiation pneumonitis 13. Absolute neutrophil count \< 1.5 x 109/L 14. Platelet count \< 100 x 109/L 15. Haemoglobin \< 80 g/L 16. Alanine aminotransferase (ALT) \> 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or \> 5 times ULN in the presence of liver metastases 17. Aspartate aminotransferase (AST) \> 2.5 times ULN if no demonstrable liver metastases or \> 5 times ULN in the presence of liver metastases 18. Total bilirubin \> 1.5 times ULN if no liver metastases or \> 3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia) or liver metastases 19. Creatinine \>1.5 times ULN concurrent with creatinine clearance \< 50 ml/min (measured or calculated by Cockcroft and Gault equation), 20. History of hypersensitivity of AZD9291 (or drugs with a similar chemical structure or class.
• \. Women who are pregnant or breast-feeding, or have a positive (urine or serum) pregnancy test prior to study entry 22. Judgment by the investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions and requirements.

Sponsors & Collaborators

• Oslo University Hospital: lead
• AstraZeneca: collaborator

Study Sites (7)

Herlev Hospital

Copenhagen, Denmark

Location

Oulu University Hospital

Oulu, Finland

Location

National Cancer Institute

Vilnius, Lithuania

Location

Drammen Hospital - Vestre Viken HF

Drammen, N-3004, Norway

Location

Norwegian Radium Hospital

Oslo, N-0309, Norway

Location

St Olavs hospital

Trondheim, N-7008, Norway

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Related Publications (1)

• Eide IJZ, Helland A, Ekman S, Mellemgaard A, Hansen KH, Cicenas S, Koivunen J, Gronberg BH, Brustugun OT. Osimertinib in T790M-positive and -negative patients with EGFR-mutated advanced non-small cell lung cancer (the TREM-study). Lung Cancer. 2020 May;143:27-35. doi: 10.1016/j.lungcan.2020.03.009. Epub 2020 Mar 12.

  PMID: 32200138 DERIVED

MeSH Terms

Conditions

Lung Neoplasms

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior consultant

Study Record Dates

• First Submitted: July 20, 2015
• First Posted: July 21, 2015
• Study Start: August 1, 2015
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: March 28, 2023

Record last verified: 2023-03

Locations

SE (1); FI (1); LI (1); NO (3); DK (1)