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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 (TREM)

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ClinicalTrials.gov Identifier: NCT02504346
Recruitment Status : Recruiting
First Posted : July 21, 2015
Last Update Posted : June 23, 2017
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Odd Terje Brustugun, Oslo University Hospital

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.

Condition or disease Intervention/treatment Phase
Lung Cancer Targeted Therapy Drug: AZD9291 Phase 2

Detailed Description:

This is a 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.

If feasible, subjects will have to provide a biopsy sample for molecular testing following confirmed disease progression on the most recent treatment regimen. A second biopsy will be sampled at progression on AZD9291, if feasible. Liquid biopsies will be sampled throughout the treatment period.

Subjects should continue on study treatment until RECIST 1.1-defined progression or until a treatment discontinuation criterion is met. There is no maximum duration of treatment as subjects may continue to receive investigational product beyond RECIST 1.1 defined progression as long as they are continuing to show clinical benefit, as judged by the investigator.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 2015
Estimated Primary Completion Date : January 2018
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Osimertinib

Arm Intervention/treatment
Experimental: Treatment
Non-randomized trial, all patients receive therapy - singel-arm
Drug: AZD9291



Primary Outcome Measures :
  1. Objective response rate [ Time Frame: 12 weeks ]
    Measured by RECIST 1.1



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of signed and dated, written informed consent.
  2. Age > 18 years.
  3. Histologically or cytologically documented locally advanced or metastatic NSCLC not amenable to curative surgery or radiotherapy.
  4. Radiological disease progression following at least one prior EGFR TKI.
  5. Documented EGFR mutation known to be associated with EGFR TKI sensitivity (also including T790M).
  6. ECOG status 0-2 and a minimum life expectancy of 12 weeks.
  7. 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.
  8. 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.
  9. Male subjects must be willing to use barrier contraception.

Exclusion Criteria:

  • 1. Treatment with an EGFR-TKI within 8 days or approximately 5x half-life, whichever is the longer, of the first dose of study treatment.

    2. 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.

    3. Previous treatment with AZD9291, or another EGFR TKI with similar profile, e.g. CO-1686 4. Major surgery within 4 weeks of inclusion 5. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of inclusion 6. Subjects currently receiving (or unable to stop using) potent inhibitors or inducers of CYP3A4 7. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 (with the exception of alopecia grade 2) at the time of starting study treatment.

    8. Spinal cord compression or brain metastases unless asymptomatic and on stable steroid dosage for at least 2 weeks prior to start of study treatment.

    9. 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.

    10. Gastrointestinal conditions incompatible with swallowing or precluding absorption of AZD9291.

    11. 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.

    21. 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02504346


Contacts
Contact: Odd Terje Brustugun, MD PhD +4799723094 ot.brustugun@gmail.com
Contact: Tina Traa, RN +4722934000 tinat@ous-hf.no

Locations
Denmark
Herlev Hospital Recruiting
Copenhagen, Denmark
Contact: Anders Mellemgaard, MD PhD         
Finland
Oulu University Hospital Recruiting
Oulu, Finland
Contact: Jussi Koivunen, MD PhD         
Lithuania
National Cancer Institute Recruiting
Vilnius, Lithuania
Contact: Saulius Cicenas, MD PhD         
Norway
Drammen Hospital - Vestre Viken HF Recruiting
Drammen, Norway, N-3004
Contact: Odd Terje Brustugun, MD PhD         
Norwegian Radium Hospital Recruiting
Oslo, Norway, N-0309
Contact: Odd Terje Brustugun, MD PhD    +4799723094    ot.brustugun@gmail.com   
Contact: Tina Traa, RN    +4722934000    tinat@ous-hf.no   
Sub-Investigator: Åslaug Helland, MD PhD         
St Olavs hospital Recruiting
Trondheim, Norway, N-7008
Contact: Bjørn Henning Gronberg, MD PhD    +4747297878    bjorn.h.gronberg@gmail.com   
Contact: Tina Traa, RN    +4722934000    tinat@ous-hf.no   
Sweden
Karolinska University Hospital Recruiting
Stockholm, Sweden
Contact: Simon Ekman, MD PhD         
Sponsors and Collaborators
Oslo University Hospital
AstraZeneca

Responsible Party: Odd Terje Brustugun, Senior consultant, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT02504346     History of Changes
Other Study ID Numbers: 2015/10301
First Posted: July 21, 2015    Key Record Dates
Last Update Posted: June 23, 2017
Last Verified: June 2017

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action