Non Small Cell Lung CancerPhase 2NCT03424759
Uncommon EGFR AZD9291
A Phase 2 study testing AZD9291 in people with Non Small Cell Lung Cancer, run by Samsung Medical Center at 1 site in South Korea.
Trial summary
EGFR (ErbB1) mutations define a lung cancer subtype with exquisite sensitivity to EGFR tyrosine kinase inhibitors (TKIs). While in-frame deletion in exon 19 (Del19) and a point mutation (L858R) in exon 21 are the two most common sensitizing EGFR mutations in NSCLC, approximately 10% of EGFR mutation-positive tumors… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- AZD9291
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteSouth Korea
- Study dates
- 1 Jan 2016to 31 Jul 2019
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed metastatic or recurrent stage IV NSCLC with activating EGFR mutation other than deletion in exon 19, L858R, T790M and insertion in exon 20
- metastatic or recurrent NSCLC
- Be 19years of age on day of signing informed consent
- ECOG performance status of 0 to 2
- At least one measurable lesion by RECIST 1.1(The part of radiation treatment in the palliative setting is excluded.)
- Untreated asymptomatic brain metastasis or symptomatic brain metastasis treated with local treatment such as operation, whole brain radiotherapy, or gamma-knife surgery
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- At least 2 weeks later after whole brain radiotherapy or at least 4 weeks later after palliative thoracic radiotherapy
- Adequate organ function as evidenced by the following; Absolute neutrophil count > 1.5 x 109/L; Hb > 9.0g/dL; platelets > 100 x 109/L; total bilirubin ≤1.5 UNL; AST and/or ALT < 2.5 ULN if no demonstrable liver metastases or < 5 UNL in the presence of liver metastases, CCr ≥ 50mL/min
- Written informed consent form
Who cannot join
- Prior treatment with EGFR TKI
- Major surgery undertaken less than 4 weeks before the study
- Localized palliative radiotherapy unless completed more than 2 weeks before the study
- Uncontrolled systemic illness such as DM, CHF, unstable angina, hypertension or arrhythmia
- Pregnant or nursing women (Women of reproductive potential have to agree to use an adequate contraceptive method)
- Uncontrolled symptomatic brain metastasis
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- Prior history of malignancy within 5 years from study entry except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, or well-treated thyroid cancer
- Concomitant use of CYP3A4 inducers/inhibitors
- Prolonged QT interval in ECG (QTc >450 msec)
- Prior history of interstitial lung disease
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine
Seoul, 135-710
About this study
Official title: An Open Label, Multicenter, Phase II Single-arm Trial of AZD9291 in Non-small Cell Lung Cancer (NSCLC) Patients With Uncommon Epidermal Growth Factor Receptor Mutations
EGFR (ErbB1) mutations define a lung cancer subtype with exquisite sensitivity to EGFR tyrosine kinase inhibitors (TKIs). While in-frame deletion in exon 19 (Del19) and a point mutation (L858R) in exon 21 are the two most common sensitizing EGFR mutations in NSCLC, approximately 10% of EGFR mutation-positive tumors harbor uncommon mutations.
These mutations represent a heterogeneous group of rare molecular alterations (or combinations) within exons 18-21, whose oncogenicity and sensitivity to EGFR TKIs may vary and has not been prospectively studied. Recently, a retrospective analysis reported that overall response rate of EGFR TKI (gefitinib or erlotinib) treatment was about 10% or less in Korean NSCLC patients with uncommon EGFR mutation other than del19, L858R and T790M [11]. In preclinical data, the potency of AZD9291 against uncommon EGFR mutants other than exon 20 insertion mutation was fairly good.
Based on the result, in this study, we try to evaluate the efficacy of AZD9291, the potent irreversible inhibitor, in NSCLC patients with harboring uncommon EGFR mutations.
Read the detailed description
This is a single-arm phase II trial to evaluate the efficacy of AZD9291 (experimental) NSCLC patients with uncommon EGFR mutation. The primary endpoint of the study is objective response rate. Recently, a retrospective analysis reported that overall response rate of EGFR TKI (gefitinib or erlotinib) treatment was about 10% or less in Korean NSCLC patients with uncommon EGFR mutation other than del19, L858R and T790M (9).
In this study, we expect an objective response rate of about 30% for the experimental arm (AZD9291 therapy) compared to that of about 10% in the historical control based on previous studies. A sample size of 33 efficacy-evaluable patients would provide a power of 90% for testing the null hypothesis of 10% ORR vs. alternative hypothesis of 30% using a single-arm exact binomial test with a 1=sided significance level of 5%. The experimental therapy will be rejected if 6 or fewer patients out of 33 respond. Allowing for a follow-up loss rate of 10%, the total sample size is 37 patients.
Patients will be treated 80 mg/day of AZD9291 orally (1 cycle for 21 days). Subjects (with the exception of subjects with insulin dependent diabetes) must fast for ≥1 hours prior to taking a dose to ≥2 hour post dose. Water is permitted during this fasting period. Cycles were repeated until disease progression, unacceptable toxicity, or until the patient or the investigator requested therapy discontinuation. If the efficacy will be proven, the patient could receive the treatment continuously.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- AZD9291
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9291Drug
Patients will be treated 80 mg/day of AZD9291 orally (1 cycle for 21 days).
| Study group | Role | What they receive |
|---|---|---|
| AZD9291 | Experimental | Patients will be treated 80 mg/day of AZD9291 orally (1 cycle for 21 days). Receives: Drug: AZD9291 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate
30%
Measured: through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2018
- Study start1 Jan 2016
- Primary completion31 Dec 2017
- Study completion31 Jul 2019 (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 Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Samsung Medical CenterThe 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
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Myung-Ju Ahn, Samsung Medical Center
- Investigators
- Myung-Ju Ahn, Principal investigator, Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03424759
- Sponsor's protocol ID
- 2015-06-176
- Status last verified
- Feb 2018
- First submitted
- 9 Jan 2018
- Last updated
- 7 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Cho JH, Lim SH, An HJ, Kim KH, Park KU, Kang EJ, Choi YH, Ahn MS, Lee MH, Sun JM, Lee SH, Ahn JS, Park K, Ahn MJ. Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09). J Clin Oncol. 2020 Feb 10;38(5):488-495. doi: 10.1200/JCO.19.00931. Epub 2019 Dec 11.
PubMed 31825714
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Multicenter, Phase II Single-arm Trial of AZD9291 in Non-small Cell Lung Cancer (NSCLC) Patients With Uncommon Epidermal Growth Factor Receptor Mutations
- ClinicalTrials.gov ID
- NCT03424759
- Acronym / sponsor ID
- 2015-06-176
- Conditions
- Non Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Study start
- 1 Jan 2016 (actual)
- Primary completion
- 31 Dec 2017 (actual)
- Study completion
- 31 Jul 2019 (estimated)
- First posted
- 7 Feb 2018 (actual)
- 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.
EGFR (ErbB1) mutations define a lung cancer subtype with exquisite sensitivity to EGFR tyrosine kinase inhibitors (TKIs). While in-frame deletion in exon 19 (Del19) and a point mutation (L858R) in exon 21 are the two most common sensitizing EGFR mutations in NSCLC, approximately 10% of EGFR mutation-positive tumors harbor uncommon mutations.
These mutations represent a heterogeneous group of rare molecular alterations (or combinations) within exons 18-21, whose oncogenicity and sensitivity to EGFR TKIs may vary and has not been prospectively studied. Recently, a retrospective analysis reported that overall response rate of EGFR TKI (gefitinib or erlotinib) treatment was about 10% or less in Korean NSCLC patients with uncommon EGFR mutation other than del19, L858R and T790M [11]. In preclinical data, the potency of AZD9291 against uncommon EGFR mutants other than exon 20 insertion mutation was fairly good.
Based on the result, in this study, we try to evaluate the efficacy of AZD9291, the potent irreversible inhibitor, in NSCLC patients with harboring uncommon EGFR mutations.
Detailed description
This is a single-arm phase II trial to evaluate the efficacy of AZD9291 (experimental) NSCLC patients with uncommon EGFR mutation. The primary endpoint of the study is objective response rate. Recently, a retrospective analysis reported that overall response rate of EGFR TKI (gefitinib or erlotinib) treatment was about 10% or less in Korean NSCLC patients with uncommon EGFR mutation other than del19, L858R and T790M (9).
In this study, we expect an objective response rate of about 30% for the experimental arm (AZD9291 therapy) compared to that of about 10% in the historical control based on previous studies. A sample size of 33 efficacy-evaluable patients would provide a power of 90% for testing the null hypothesis of 10% ORR vs. alternative hypothesis of 30% using a single-arm exact binomial test with a 1=sided significance level of 5%. The experimental therapy will be rejected if 6 or fewer patients out of 33 respond. Allowing for a follow-up loss rate of 10%, the total sample size is 37 patients.
Patients will be treated 80 mg/day of AZD9291 orally (1 cycle for 21 days). Subjects (with the exception of subjects with insulin dependent diabetes) must fast for ≥1 hours prior to taking a dose to ≥2 hour post dose. Water is permitted during this fasting period. Cycles were repeated until disease progression, unacceptable toxicity, or until the patient or the investigator requested therapy discontinuation. If the efficacy will be proven, the patient could receive the treatment continuously.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AZD9291 | Experimental | Drug: AZD9291Patients will be treated 80 mg/day of AZD9291 orally (1 cycle for 21 days). |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically confirmed metastatic or recurrent stage IV NSCLC with activating EGFR mutation other than deletion in exon 19, L858R, T790M and insertion in exon 20
- metastatic or recurrent NSCLC
- Be 19years of age on day of signing informed consent
- ECOG performance status of 0 to 2
- At least one measurable lesion by RECIST 1.1(The part of radiation treatment in the palliative setting is excluded.)
Key exclusion criteria (10 listed)
- Prior treatment with EGFR TKI
- Major surgery undertaken less than 4 weeks before the study
- Localized palliative radiotherapy unless completed more than 2 weeks before the study
- Uncontrolled systemic illness such as DM, CHF, unstable angina, hypertension or arrhythmia
- Pregnant or nursing women (Women of reproductive potential have to agree to use an adequate contraceptive method)
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 |
|---|---|---|
| AZD9291Patients will be treated 80 mg/day of AZD9291 orally (1 cycle for 21 days). | Drug | AZD9291 |
Primary outcome
Objective response rate
Time frame: through study completion, an average of 2 years
30%
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2018.
- Derived from this study: PubMed 31825714Cho JH, Lim SH, An HJ, Kim KH, Park KU, Kang EJ, Choi YH, Ahn MS, Lee MH, Sun JM, Lee SH, Ahn JS, Park K, Ahn MJ. Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09). J Clin Oncol. 2020 Feb 10;38(5):488-495. doi: 10.1200/JCO.19.00931. Epub 2019 Dec 11.
- Individual participant dataSharing planned: Undecided
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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.
Myung-Ju Ahn principal investigator
Samsung Medical Center
1 site in 1 country: 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 Non Small Cell Lung Cancer, run by Samsung Medical Center at 1 site in South Korea.
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 9 inclusion and 10 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 7 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. 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: through study completion, an average of 2 years). 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 NCT03424759, 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 7 Feb 2018.