EGFR-TKI-naïve Patients With NSCLC Harboring EGFR Activating MutationsPhase 2NCT02500927
A Study of ASP8273 in Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor-Naïve Patients With Non-Small Cell Lung Cancer Harboring EGFR Mutations
A Phase 2 study testing ASP8273 Capsules and ASP8273 Capsules A in people with EGFR-TKI-naïve Patients With NSCLC Harboring EGFR Activating Mutations, run by Astellas Pharma Inc at 11 sites in Japan.
Trial summary
The purpose of this study is to determine the safety, the antitumor activity and the pharmacokinetics of ASP8273 in EGFR tyrosine kinase inhibitor (EGFR-TKI)-naïve patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- EGFR-TKI-naïve Patients With NSCLC Harboring EGFR Activating Mutations
- What is being tested?
- ASP8273 Capsules and ASP8273 Capsules A
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 11 sitesJapan
- Study dates
- 25 Jun 2015to 9 Jun 2017
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
- Patients with a histologically or cytologically confirmed diagnosis of Stage IIIB or IV NSCLC.
- Patients confirmed to have the deletion of exon 19 (del ex19), L858R, G719X, or L861Q mutation among the EGFR activating mutations (patients at the study site who are documented to have any of the above-stated EGFR activating mutations can be enrolled in the study).
- Patients with a life expectancy ≥ 12 weeks based on the principal investigator's/subinvestigator's judgment.
- Patients who meet all of the following requirements for laboratory tests within 7 days before enrollment. When 2 or more test results for a single parameter are found within the specified period, the last data before enrollment should be used for assessment.
- Neutrophil count: ≥ 1,500/mm3
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- Platelet count: ≥ 75,000/mm3
- Hemoglobin: ≥ 9 g/dL
- Serum creatinine: < 1.5 mg/dL
- Total bilirubin (TBL): < 1.5 × the upper limit of normal (ULN) at the site (this does not apply to patients with Gilbert syndrome)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): < 2.5 ×the ULN at the site
- Patients who meet all the following requirements for prior treatment for NSCLC:
- Patients who have not received previous treatment with EGFR-TKIs*1 *1: Erlotinib, gefitinib, afatinib, and EGFR-TKIs under clinical investigation (e.g.,neratinib, dacomitinib). EGFR-TKIs that can inhibit EGFR with the T790Mmutation (e.g., ASP8273, CO-1686, AZD9291) are also included.
- Patients who have not received more than one regimen of previous drug treatment (however, this does not include preoperative or postoperative therapies used within at least a 6-month interval after the last dose of the treatment).
- Patients who have at least 1 measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Who cannot join
- Patients with persistent clinical evidence of previous antitumor treatment-related toxicity ≥ Grade 2 using the Japan Clinical Oncology Group (JCOG) Japanese translation of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (NCI CTCAE v4.0 - JCOG) (except alopecia).
- Patients with a history of or concurrent interstitial lung disease.
- Patients who have received previous treatment with intended antitumor effects or treatment with another investigational drug/medical device within 14 days before the start of the study treatment.
- Patients who have received transfusion or hematopoietic growth factor therapy within 14 days prior to the start of the study treatment.
- Patients who have received oral or intravenous corticosteroids within 7 days prior to the start of the study treatment (except to treat or prevent an allergic reaction).
- Patients who are scheduled to undergo a surgical procedure during the course of the study or the patient still has an unhealed wound after previous surgery.
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- Patients with a positive test for hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (anti-HCV).
- Patients with a known history of a positive test for human immunodeficiency virus (HIV) infection.
- Patients with symptomatic central nervous system (CNS) lesions.
- Patients with a known history of serious drug hypersensitivity.
- Patients with evidence of active infection requiring systemic drug therapy within 14 days prior to the start of the study treatment.
- Patients who have received strong CYP3A inhibitors within 9 days prior to the start of the study treatment (for itraconazole, within 14 days prior to the start of the study treatment).
- Patients who have received moderate CYP3A inhibitors within 9 days prior to the start of the study treatment (only for subjects included in BA evaluation).
- Patients who have received strong or moderate CYP3A inducers within 14 days prior to the start of the study treatment (only for subjects included in BA evaluation).
- Patients with prolongation of the QTc interval (male: ≥ 451 ms, female: ≥ 471 ms) on the 12-lead electrocardiogram (ECG) in the screening period.
- Patients with cardiac arrhythmias requiring treatment.
- Patients with Class 3 or 4 New York Heart Association (NYHA) congestive heart failure.
- Patients with a history of acute coronary syndrome, myocardial infarction, or cerebrovascular accident within 6 months prior to enrollment.
- Patients with a history of or concurrent active peptic ulcer disease or gastrointestinal bleeding within 3 months prior to enrollment.
- Patients with corneal disease ≥ Grade 2.
- Patients with difficulty to take oral medication, or any gastrointestinal malfunction or inflammatory bowel disease that is considered to affect drug absorption.
- Patients with active multiple cancers (simultaneous multiple cancers).
- Patients with other conditions ineligible for participation in the study based on the principal investigator's/sub-investigator's judgment.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
Japan11 sites
Site: 5
Fukuoka
Site: 9
Hiroshima
Site: 8
Hyōgo
Site: 7
Kanagawa
Site: 11
Miyagi
Site: 1
Miyagi
Site: 10
Nagoya
Site: 4
Okayama
Site: 3
Osaka
Site: 6
Osaka
Site: 2
Tokyo
About this study
Official title: Phase II Study of ASP8273 - An Open-Label, Study of the Oral Administration of ASP8273 in Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor-NaïvePatients With Non-Small Cell Lung Cancer Harboring EGFR Mutations
The purpose of this study is to determine the safety, the antitumor activity and the pharmacokinetics of ASP8273 in EGFR tyrosine kinase inhibitor (EGFR-TKI)-naïve patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations.
Read the detailed description
This study consists of a single-dose period (Cycle 0 lasting 3 days) and a multiple-dose period (from Cycle 1 onwards, each cycle lasting 21 days). To compare the PK between ASP8273 Capsules and ASP8273 Capsules A, enrolled subjects will receive a single oral dose of ASP8273 Capsules A on Day 1 of Cycle 0 in the single-dose period and will then be observed for 3 days (including the day of dosing). In the multiple-dose period, subjects will receive multiple oral doses of ASP8273 Capsules during each cycle lasting 21 days. From the viewpoint of PK comparison (bioavailability [BA] evaluation) between ASP8273 Capsules and ASP8273 Capsules A, data from approximately 15 subjects are sufficient for the evaluation. Therefore, if PK data of approximately 15 subjects included in BA evaluation are obtained and the sponsor judges that further acquisition of PK data is not necessary, the single-dose period will not be conducted in subjects who are enrolled thereafter (subjects not included in BA evaluation). Subjects will continue to receive treatment with ASP8273 until they meet the discontinuation criteria.
- Being tested
- ASP8273 Capsules, ASP8273 Capsules A
- Keywords
- ASP8273, Non-Small Cell Lung Cancer, EGFR Tyrosine Kinase Inhibitor, EGFR Mutation
- 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.
ASP8273 CapsulesDrug
oral
ASP8273 Capsules ADrug
oral
| Study group | Role | What they receive |
|---|---|---|
| ASP8273 group | Experimental | Single oral administration of ASP8273 Capsule A for bioavailability evaluation, followed once daily multiple administration of ASP8273 Capsule Receives: Drug: ASP8273 Capsules; Drug: ASP8273 Capsules A |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety assessed by AEs
Measured: Up to 18 months
Safety assessed by Laboratory tests
Measured: Up to 18 months
Safety assessed by Vital signs
Measured: Up to 18 months
Safety assessed by Percutaneous oxygen saturation (SpO2)
Measured: Up to 18 months
Safety assessed by Body weight
Measured: Up to 18 months
Safety assessed by 12-lead ECG
ECG: Electrocardiogram
Measured: Up to 18 months
Safety assessed by Ophthalmologic examination
Measured: Up to 18 months
Safety assessed by Chest X-ray examination
Measured: Up to 18 months
Safety assessed by Chest computed tomography (CT) examination
Measured: Up to 18 months
Safety assessed by ECOG Performance Status
Measured: Up to 18 months
Secondary outcomes (3)
Overall response rate
The overall response rate is defined as the proportion of subjects whose best overall response is rated as Complete response (CR) or Partial Response (PR)among all analyzed subjects
Measured: Up to 18 months
Disease control rate
The disease control rate is defined as the proportion of subjects whose best overall response is rated as Complete response (CR), Partial Response (PR), or Stable disease (SD) among all analyzed subjects
Measured: Up to 18 months
Plasma concentrations of unchanged ASP8273
Measured: Up to Day1 of Cycle 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2015 (estimated)
- Study start25 Jun 2015
- Primary completion9 Jun 2017
- Study completion9 Jun 2017
Why it stopped: Following recommendation by SOLAR Study IDMC, Astellas closed enrollment in ASP8273 studies.
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 EGFR-TKI-naïve Patients With NSCLC Harboring EGFR Activating MutationsStudies of the same condition, open and under way.
- 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
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Astellas Pharma Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02500927
- Sponsor's protocol ID
- 8273-CL-0202
- Status last verified
- Nov 2024
- First submitted
- 25 Jun 2015
- Last updated
- 20 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
Publications
Azuma K, Nishio M, Hayashi H, Kiura K, Satouchi M, Sugawara S, Hida T, Iwamoto Y, Inoue A, Takeda K, Ikeda S, Nakagawa T, Takeda K, Asahina S, Komatsu K, Morita S, Fukuoka M, Nakagawa K. ASP8273 tolerability and antitumor activity in tyrosine kinase inhibitor-naive Japanese patients with EGFR mutation-positive non-small-cell lung cancer. Cancer Sci. 2018 Aug;109(8):2532-2538. doi: 10.1111/cas.13651. Epub 2018 Jun 29.
PubMed 29807396
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of ASP8273 - An Open-Label, Study of the Oral Administration of ASP8273 in Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor-NaïvePatients With Non-Small Cell Lung Cancer Harboring EGFR Mutations
- ClinicalTrials.gov ID
- NCT02500927
- Acronym / sponsor ID
- 8273-CL-0202
- Keywords
- ASP8273, Non-Small Cell Lung Cancer, EGFR Tyrosine Kinase Inhibitor, EGFR Mutation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Following recommendation by SOLAR Study IDMC, Astellas closed enrollment in ASP8273 studies.
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Astellas Pharma IncIndustry (pharma, biotech, devices)
- Study start
- 25 Jun 2015 (actual)
- Primary completion
- 9 Jun 2017 (actual)
- Study completion
- 9 Jun 2017 (actual)
- First posted
- 17 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.
The purpose of this study is to determine the safety, the antitumor activity and the pharmacokinetics of ASP8273 in EGFR tyrosine kinase inhibitor (EGFR-TKI)-naïve patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations.
Detailed description
This study consists of a single-dose period (Cycle 0 lasting 3 days) and a multiple-dose period (from Cycle 1 onwards, each cycle lasting 21 days). To compare the PK between ASP8273 Capsules and ASP8273 Capsules A, enrolled subjects will receive a single oral dose of ASP8273 Capsules A on Day 1 of Cycle 0 in the single-dose period and will then be observed for 3 days (including the day of dosing). In the multiple-dose period, subjects will receive multiple oral doses of ASP8273 Capsules during each cycle lasting 21 days. From the viewpoint of PK comparison (bioavailability [BA] evaluation) between ASP8273 Capsules and ASP8273 Capsules A, data from approximately 15 subjects are sufficient for the evaluation. Therefore, if PK data of approximately 15 subjects included in BA evaluation are obtained and the sponsor judges that further acquisition of PK data is not necessary, the single-dose period will not be conducted in subjects who are enrolled thereafter (subjects not included in BA evaluation). Subjects will continue to receive treatment with ASP8273 until they meet the discontinuation criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ASP8273 group | Experimental | Drug: ASP8273 Capsules, Drug: ASP8273 Capsules ASingle oral administration of ASP8273 Capsule A for bioavailability evaluation, followed once daily multiple administration of ASP8273 Capsule |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
- Patients with a histologically or cytologically confirmed diagnosis of Stage IIIB or IV NSCLC.
- Patients confirmed to have the deletion of exon 19 (del ex19), L858R, G719X, or L861Q mutation among the EGFR activating mutations (patients at the study site who are documented to have any of the above-stated EGFR activating mutations can be enrolled in the study).
- Patients with a life expectancy ≥ 12 weeks based on the principal investigator's/subinvestigator's judgment.
- Patients who meet all of the following requirements for laboratory tests within 7 days before enrollment. When 2 or more test results for a single parameter are found within the specified period, the last data before enrollment should be used for assessment.
Key exclusion criteria (23 listed)
- Patients with persistent clinical evidence of previous antitumor treatment-related toxicity ≥ Grade 2 using the Japan Clinical Oncology Group (JCOG) Japanese translation of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (NCI CTCAE v4.0 - JCOG) (except alopecia).
- Patients with a history of or concurrent interstitial lung disease.
- Patients who have received previous treatment with intended antitumor effects or treatment with another investigational drug/medical device within 14 days before the start of the study treatment.
- Patients who have received transfusion or hematopoietic growth factor therapy within 14 days prior to the start of the study treatment.
- Patients who have received oral or intravenous corticosteroids within 7 days prior to the start of the study treatment (except to treat or prevent an allergic reaction).
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 |
|---|---|---|
| ASP8273 Capsulesoral | Drug | ASP8273 group |
| ASP8273 Capsules Aoral | Drug | ASP8273 group |
Primary outcome
Safety assessed by AEs
Time frame: Up to 18 months
Safety assessed by Laboratory tests
Time frame: Up to 18 months
Safety assessed by Vital signs
Time frame: Up to 18 months
Safety assessed by Percutaneous oxygen saturation (SpO2)
Time frame: Up to 18 months
Safety assessed by Body weight
Time frame: Up to 18 months
Safety assessed by 12-lead ECG
Time frame: Up to 18 months
ECG: Electrocardiogram
Safety assessed by Ophthalmologic examination
Time frame: Up to 18 months
Safety assessed by Chest X-ray examination
Time frame: Up to 18 months
Safety assessed by Chest computed tomography (CT) examination
Time frame: Up to 18 months
Safety assessed by ECOG Performance Status
Time frame: Up to 18 months
3 secondary outcomes
Overall response rate
Time frame: Up to 18 months
Disease control rate
Time frame: Up to 18 months
Plasma concentrations of unchanged ASP8273
Time frame: Up to Day1 of Cycle 3
Results and safety
The study was stopped early (reason given: Following recommendation by SOLAR Study IDMC, Astellas closed enrollment in ASP8273 studies.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2024.
- Derived from this study: PubMed 29807396Azuma K, Nishio M, Hayashi H, Kiura K, Satouchi M, Sugawara S, Hida T, Iwamoto Y, Inoue A, Takeda K, Ikeda S, Nakagawa T, Takeda K, Asahina S, Komatsu K, Morita S, Fukuoka M, Nakagawa K. ASP8273 tolerability and antitumor activity in tyrosine kinase inhibitor-naive Japanese patients with EGFR mutation-positive non-small-cell lung cancer. Cancer Sci. 2018 Aug;109(8):2532-2538. doi: 10.1111/cas.13651. Epub 2018 Jun 29.
- Individual participant dataSharing planned: No. Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
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.
Medical Director study director
Astellas Pharma Inc
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ASP8273 Capsules and ASP8273 Capsules A in people with EGFR-TKI-naïve Patients With NSCLC Harboring EGFR Activating Mutations, run by Astellas Pharma Inc at 11 sites in Japan.
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 15 inclusion and 23 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: stopped early, as of the sponsor's last update on 20 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Japan. 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?
The study was stopped early (reason given: Following recommendation by SOLAR Study IDMC, Astellas closed enrollment in ASP8273 studies.). 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?
Safety assessed by AEs (time frame: Up to 18 months). The study lists 10 primary outcomes in all. 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 NCT02500927, 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 20 Nov 2024.