Untreated Advanced NSCLC PatientsNCT04499794
The Study of Exosome EML4-ALK Fusion in NSCLC Clinical Diagnosis and Dynamic Monitoring
An observational study of Untreated Advanced NSCLC Patients and FISH Identified ALK Fusion Positive or Negative, run by Chinese Academy of Medical Sciences at 1 site in China.
Trial summary
The application of ALK inhibitors in the first-line cancer treatment can significantly increase the PFS and ORR of patients those with EML4-ALK fusion. The contemporary clinical ALK fusion detection are mainly via FISH and ICH while biopsies are needed. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Untreated Advanced NSCLC Patients, FISH Identified ALK Fusion Positive or Negative
- What is being tested?
- ALK inhibitor
- How many people
- 75 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2020to 31 Mar 2025
- Phase
- Observational
- 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
Study population: advanced NSCLC patients
Who may be able to join
- All eligible patients must have histologically or cytologically confirmed stage IIIB-IV unresectable NSCLC positive or negative for EML4-ALK4 fusion as defined by FISH. Patients must have an ECOG PS of 0- 1 and have at least 1 measurable lesions (RECIST 1.1 standard). For eligible patients, prior ALK inhibitor therapy or previous systemic anticancer therapy is not allowed or has been completed over 12 months. Patients with brain metastasis are eligible only in a stable central nervous system condition and treatment outcome, cannot receive glucocorticoids and drugs prohibited in the exclusion criteria ≤14 days before the first dose of study drug.
Who cannot join
- Eligible patients must not have received any major surgery ≤28 days before the first dose of study drug and must not have received any minor surgery or radiotherapy ≤14 days before the first dose of study drug. Any acute toxic reaction must have recovered to ≤ Grade 1 (except for hair loss). Patients with carcinomatous meningitis, leptomeningeal disease or spinal cord compression must be excluded.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, 100021
Yutao LIU, Doctor, 13911901165, 13911901165@139.com
About this study
The application of ALK inhibitors in the first-line cancer treatment can significantly increase the PFS and ORR of patients those with EML4-ALK fusion. The contemporary clinical ALK fusion detection are mainly via FISH and ICH while biopsies are needed. For locations where are difficult to take biopsies, these routine examinations can hardly been adopted. Apart from these, part of ALK fusion patients are resistant to ALK inhibitors, also making an accurate and efficient prognostic indicator for efficacy evaluation and identifying high-risk recurrent population an urgent priority.
The bilayer membrane structure of exosome helps maintain its internal genetic stability, making detection of EML4-ALK fusion via plasma exosomes in advanced NSCLC patients a feasible way, which might provide a non-invasive and more convenient approach for NSCLC diagnosis and efficacy monitoring. Firstly, this study will evaluate the performance of exosome EML4-ALK fusion detection in NSCLC diagnosis, which sensitivity and specificity would be compared with the FDA approved IHC (ALK [D5F3] CDx Assay) test. Subsequently, this study would monitor the dynamic changes of EML4-ALK fusion in exosome examination diagnosed ALK fusion positive NSCLC patients both before and after treatment. It aims to prospectively evaluate the potential value of this approach on efficacy and prognosis prediction in NSCLC therapy and determining whether exosome ALK fusion could assess the curative effect more accurately than imaging examination and tumor markers. Thirdly, FISH diagnosed EML4-ALK positive NSCLC patients will be divided into the positive or negative subgroup according to their post-treatment exosome ALK fusion expression which were determined at 2-3 months after ALK inhibitor were adopted. The prognostic value of monitoring exosome EML4-ALK fusion expression is assessed through the comparison of patients PFS and OS.
- Being tested
- ALK inhibitor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALK inhibitorDrug
ALK inhibitor treatment on ALK fusion positive NSCLC patients
| Study group | Role | What they receive |
|---|---|---|
| FISH diagnosed EML4-ALK fusion positive NSCLC group | Not described Receives: Drug: ALK inhibitor | |
| FISH diagnosed EML4-ALK fusion negative NSCLC group | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR
the ORR of those NSCLC patients receive ALK inhibitors treatment according to exosome ALK fusion diagnosis and FISH examination
Measured: 6-8 weeks
Secondary outcomes (1)
PFS
the PFS of those NSCLC patients receive ALK inhibitors treatment according to exosome ALK fusion diagnosis and FISH examination
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2020
- Study start1 Aug 2020 (estimated)
- Primary completion31 Jul 2024 (estimated)
- Study completion31 Mar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Untreated Advanced NSCLC PatientsStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese Academy of Medical Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yutao Liu, Chinese Academy of Medical Sciences
- Investigators
- Yutao LIU, Doctor, Principal investigator, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04499794
- Sponsor's protocol ID
- NCC2064
- Status last verified
- Jul 2020
- First submitted
- 31 Jul 2020
- Last updated
- 5 Aug 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Hyun KA, Kim J, Gwak H, Jung HI. Isolation and enrichment of circulating biomarkers for cancer screening, detection, and diagnostics. Analyst. 2016 Jan 21;141(2):382-92. doi: 10.1039/c5an01762a.
PubMed 26588824Cazzoli R, Buttitta F, Di Nicola M, Malatesta S, Marchetti A, Rom WN, Pass HI. microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J Thorac Oncol. 2013 Sep;8(9):1156-62. doi: 10.1097/JTO.0b013e318299ac32.
PubMed 23945385Castellanos-Rizaldos E, Zhang X, Tadigotla VR, Grimm DG, Karlovich C, Raez LE, Skog JK. Exosome-based detection of activating and resistance EGFR mutations from plasma of non-small cell lung cancer patients. Oncotarget. 2019 Apr 23;10(30):2911-2920. doi: 10.18632/oncotarget.26885. eCollection 2019 Apr 23.
PubMed 31080561Tong Y, Zhao Z, Liu B, Bao A, Zheng H, Gu J, McGrath M, Xia Y, Tan B, Song C, Li Y. 5'/ 3' imbalance strategy to detect ALK fusion genes in circulating tumor RNA from patients with non-small cell lung cancer. J Exp Clin Cancer Res. 2018 Mar 27;37(1):68. doi: 10.1186/s13046-018-0735-1.
PubMed 29587818
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Study of Exosome EML4-ALK Fusion in NSCLC Clinical Diagnosis and Dynamic Monitoring
- ClinicalTrials.gov ID
- NCT04499794
- Acronym / sponsor ID
- NCC2064
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- 1 Aug 2020 (estimated)
- Primary completion
- 31 Jul 2024 (estimated)
- Study completion
- 31 Mar 2025 (estimated)
- First posted
- 5 Aug 2020 (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.
The application of ALK inhibitors in the first-line cancer treatment can significantly increase the PFS and ORR of patients those with EML4-ALK fusion. The contemporary clinical ALK fusion detection are mainly via FISH and ICH while biopsies are needed. For locations where are difficult to take biopsies, these routine examinations can hardly been adopted. Apart from these, part of ALK fusion patients are resistant to ALK inhibitors, also making an accurate and efficient prognostic indicator for efficacy evaluation and identifying high-risk recurrent population an urgent priority.
The bilayer membrane structure of exosome helps maintain its internal genetic stability, making detection of EML4-ALK fusion via plasma exosomes in advanced NSCLC patients a feasible way, which might provide a non-invasive and more convenient approach for NSCLC diagnosis and efficacy monitoring. Firstly, this study will evaluate the performance of exosome EML4-ALK fusion detection in NSCLC diagnosis, which sensitivity and specificity would be compared with the FDA approved IHC (ALK [D5F3] CDx Assay) test. Subsequently, this study would monitor the dynamic changes of EML4-ALK fusion in exosome examination diagnosed ALK fusion positive NSCLC patients both before and after treatment. It aims to prospectively evaluate the potential value of this approach on efficacy and prognosis prediction in NSCLC therapy and determining whether exosome ALK fusion could assess the curative effect more accurately than imaging examination and tumor markers. Thirdly, FISH diagnosed EML4-ALK positive NSCLC patients will be divided into the positive or negative subgroup according to their post-treatment exosome ALK fusion expression which were determined at 2-3 months after ALK inhibitor were adopted. The prognostic value of monitoring exosome EML4-ALK fusion expression is assessed through the comparison of patients PFS and OS.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FISH diagnosed EML4-ALK fusion positive NSCLC group | – | Drug: ALK inhibitor |
| FISH diagnosed EML4-ALK fusion negative NSCLC group | – | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- advanced NSCLC patients
Key inclusion criteria (1 listed)
- All eligible patients must have histologically or cytologically confirmed stage IIIB-IV unresectable NSCLC positive or negative for EML4-ALK4 fusion as defined by FISH. Patients must have an ECOG PS of 0- 1 and have at least 1 measurable lesions (RECIST 1.1 standard). For eligible patients, prior ALK inhibitor therapy or previous systemic anticancer therapy is not allowed or has been completed over 12 months. Patients with brain metastasis are eligible only in a stable central nervous system condition and treatment outcome, cannot receive glucocorticoids and drugs prohibited in the exclusion criteria ≤14 days before the first dose of study drug.
Key exclusion criteria (1 listed)
- Eligible patients must not have received any major surgery ≤28 days before the first dose of study drug and must not have received any minor surgery or radiotherapy ≤14 days before the first dose of study drug. Any acute toxic reaction must have recovered to ≤ Grade 1 (except for hair loss). Patients with carcinomatous meningitis, leptomeningeal disease or spinal cord compression must be excluded.
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 |
|---|---|---|
| ALK inhibitorALK inhibitor treatment on ALK fusion positive NSCLC patients | Drug | FISH diagnosed EML4-ALK fusion positive NSCLC group |
Primary outcome
ORR
Time frame: 6-8 weeks
the ORR of those NSCLC patients receive ALK inhibitors treatment according to exosome ALK fusion diagnosis and FISH examination
1 secondary outcome
PFS
Time frame: 36 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2020.
- Background: PubMed 26588824Hyun KA, Kim J, Gwak H, Jung HI. Isolation and enrichment of circulating biomarkers for cancer screening, detection, and diagnostics. Analyst. 2016 Jan 21;141(2):382-92. doi: 10.1039/c5an01762a.
- Background: PubMed 23945385Cazzoli R, Buttitta F, Di Nicola M, Malatesta S, Marchetti A, Rom WN, Pass HI. microRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J Thorac Oncol. 2013 Sep;8(9):1156-62. doi: 10.1097/JTO.0b013e318299ac32.
- Background: PubMed 31080561Castellanos-Rizaldos E, Zhang X, Tadigotla VR, Grimm DG, Karlovich C, Raez LE, Skog JK. Exosome-based detection of activating and resistance EGFR mutations from plasma of non-small cell lung cancer patients. Oncotarget. 2019 Apr 23;10(30):2911-2920. doi: 10.18632/oncotarget.26885. eCollection 2019 Apr 23.
- Background: PubMed 29587818Tong Y, Zhao Z, Liu B, Bao A, Zheng H, Gu J, McGrath M, Xia Y, Tan B, Song C, Li Y. 5'/ 3' imbalance strategy to detect ALK fusion genes in circulating tumor RNA from patients with non-small cell lung cancer. J Exp Clin Cancer Res. 2018 Mar 27;37(1):68. doi: 10.1186/s13046-018-0735-1.
- 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.
Yutao LIU, Doctor principal investigator
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Untreated Advanced NSCLC Patients and FISH Identified ALK Fusion Positive or Negative, run by Chinese Academy of Medical Sciences at 1 site in China.
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 1 inclusion and 1 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 5 Aug 2020. 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 China. 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.
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?
Contact Yutao LIU, Doctor (+86 13911901165, 13911901165@139.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR (time frame: 6-8 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 NCT04499794, which also lists 4 linked publications.
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 5 Aug 2020.