Lung CancerPhase 2TREMNCT02504346
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
A Phase 2 study testing AZD9291 in people with Lung Cancer and Targeted Therapy, run by Oslo University Hospital at 7 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer, Targeted Therapy
- What is being tested?
- AZD9291
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 7 sitesin 5 countries
- Study dates
- Aug 2015to Jun 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 13Show fewer
- 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.
- -
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
Norway3 sites
Drammen Hospital - Vestre Viken HF
Drammen, N-3004
Norwegian Radium Hospital
Oslo, N-0309
St Olavs hospital
Trondheim, N-7008
About this study
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.
Read the 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.
- Conditions
- Lung Cancer, Targeted Therapy
- Being tested
- AZD9291
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9291Drug
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Non-randomized trial, all patients receive therapy - singel-arm Receives: Drug: AZD9291 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate
Measured by RECIST 1.1
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2015 (estimated)
- Study startAug 2015
- Primary completion1 Jun 2023 (estimated)
- Study completionJun 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lung CancerStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Odd Terje Brustugun, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02504346
- Sponsor's protocol ID
- 2015/10301
- Other IDs
- 2015
- Acronym
- TREM
- Status last verified
- Mar 2023
- First submitted
- 20 Jul 2015
- Last updated
- 28 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 32200138
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02504346
- Acronym / sponsor ID
- TREM / 2015/10301
- Conditions
- Lung Cancer, Targeted Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Aug 2015 (actual)
- Primary completion
- 1 Jun 2023 (estimated)
- Study completion
- Jun 2023 (estimated)
- First posted
- 21 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: AZD9291Non-randomized trial, all patients receive therapy - singel-arm |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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).
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD9291 | Drug | Treatment |
Primary outcome
Objective response rate
Time frame: 12 weeks
Measured by RECIST 1.1
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2023.
- Derived from this study: PubMed 32200138Eide 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.
Related trials for Lung Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
Non Small Cell Lung Cancer
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 3
A Study Evaluating Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Participants With Stage IV or Advanced Stage IIIB/C Nonsquamous Non-Small Cell Lung Cancers (CodeBreaK 202)
Non-Small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 2
Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer
Metastatic Lung Cancer, Advanced Non Small Cell Lung Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AZD9291 in people with Lung Cancer and Targeted Therapy, run by Oslo University Hospital at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Norway, Denmark, Finland, Lithuania, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02504346, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2023; AzTrials last refreshed its copy on 7 Nov 2026.