Unresectable or Metastatic Non-small Cell Lung Cancer (NSCLC)NCT00579683
Registry for Patients With Acquired Resistance to Small Molecule Kinase Inhibitors in Non-Small-Cell Lung Cancer
An observational study of Unresectable or Metastatic Non-small Cell Lung Cancer (NSCLC), run by Memorial Sloan Kettering Cancer Center at 5 sites in United States.
Trial summary
The purpose of this study is to try to learn more about how small molecule kinase inhibitors work in treating lung cancer. Some early studies have shown that gefitinib, erlotinib and similar drugs are more likely to work if a particular DNA change (also known as a mutation) is found in a protein that is important in… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Unresectable or Metastatic Non-small Cell Lung Cancer (NSCLC)
- What is being tested?
- Tumor core biopsy for RNA isolation
- How many people
- 228 participants
- Where
- 5 sitesUnited States
- Study dates
- Aug 2004to Feb 2016
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Unresectable or metastatic non-small cell lung cancer (NSCLC)
Who may be able to join
- Patients diagnosed with unresectable or metastatic non-small cell lung cancer (NSCLC) and who fulfill the following eligibility criteria will be considered eligible for this study.
- Patient must have previously received treatment with small molecule kinase inhibitors targeting at least, in part, EGFR patients may have received other treatments since treatment with small molecule kinase inhibitors including radiation or chemotherapy)
- Development of disease progression while actively receiving tyrosine kinase inhibitor
- Signed informed consent
Who cannot join
- None
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey
Memorial Sloan-Kettering Cancer Center @ Suffolk
Commack, New York, 11725
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Sloan-Kettering at Mercy Medical Center
Rockville Centre, New York
Memoral Sloan Kettering Cancer Center at Phelps
Sleepy Hollow, New York, 10591
About this study
Official title: A Prospective Registry for Patients With Acquired Resistance to Small Molecule Kinase Inhibitors in Non-Small-Cell Lung Cancer
The purpose of this study is to try to learn more about how small molecule kinase inhibitors work in treating lung cancer. Some early studies have shown that gefitinib, erlotinib and similar drugs are more likely to work if a particular DNA change (also known as a mutation) is found in a protein that is important in lung cancer. This protein is called the epidermal growth factor receptor (EGFR). Since small molecule kinase inhibitors sometimes stop working, we would like to examine your tumor to learn why these medicines are not working as well. Your tumor will be examined for a variety of things including changes in the DNA of the EGFR. We will also sequence parts of the genes for HER2, HER3, HER4, and KRAS, other proteins thought to be important in lung cancer.
Read the detailed description
The goal of this protocol is to determine mechanisms of resistance to epidermal growth factor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer (NSCLC). A number of trials have shown small molecule kinase inhibitors to be active agents in the treatment of NSCLC [1]. Clinically these drugs have been noted to produce dramatic but infrequent responses. Mutations in the epidermal growth factor receptor have been shown to correlate with sensitivity to gefitinib and erlotinib[2,3]. However, we know that most patients who have initial responses to EGFR-TKI eventually progress. The mechanism of acquired clinical resistance to these inhibitors in patients incompletely understood.
This is a protocol to study clinical characteristics and biopsy tissue of patients with non-small cell lung cancer who have had previous clinical response to small molecule kinase inhibitors and subsequently experience progression of disease. The tissues and other specimens will be used to carry out laboratory studies to explore the molecular basis of sensitivity and resistance to small molecule kinase inhibitors.
- Being tested
- Tumor core biopsy for RNA isolation
- Keywords
- non-small cell lung cancer, NSCLC, metastatic disease, resistent disease, RNA analysis, 04-103
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tumor core biopsy for RNA isolationOther
RNA isolation will be carried out using approximately 25 mg of gross tissue from these tumor specimens.
| Study group | Role | What they receive |
|---|---|---|
| 1 | This is a protocol to study tissue specimens to identify changes in tumor DNA in NSCLC patients who have previously responded to therapy and who have subsequently experienced disease progression. Receives: Other: Tumor core biopsy for RNA isolation |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare EGFR gene sequence in patients upon relapse with EGFR gene sequence prior to treatment with small molecule kinase inhibitors.
Measured: 2 years
Secondary outcomes (3)
To identify novel mutations in the tyrosine kinase domain of EGFR in patients with acquired resistance to small molecule kinase inhibitors.
Measured: 2 years
To more precisely characterize the frequency and clinical implications of T790M in patients with acquired resistance to small molecule kinase inhibitors.
Measured: 2 years
To identify novel mechanisms of acquired resistance to EGFR small molecule kinase inhibitors.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2007 (estimated)
- Study startAug 2004
- Primary completionFeb 2016
- Study completionFeb 2016
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 Unresectable or Metastatic Non-small Cell Lung Cancer (NSCLC)Studies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 228 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Helena Yu, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00579683
- Sponsor's protocol ID
- 04-103
- Status last verified
- Feb 2016
- First submitted
- 20 Dec 2007
- Last updated
- 4 Feb 2016
- Results posted
- No
Publications
Oxnard GR, Arcila ME, Sima CS, Riely GJ, Chmielecki J, Kris MG, Pao W, Ladanyi M, Miller VA. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res. 2011 Mar 15;17(6):1616-22. doi: 10.1158/1078-0432.CCR-10-2692. Epub 2010 Dec 6.
PubMed 21135146
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Registry for Patients With Acquired Resistance to Small Molecule Kinase Inhibitors in Non-Small-Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT00579683
- Acronym / sponsor ID
- 04-103
- Keywords
- non-small cell lung cancer, NSCLC, metastatic disease, resistent disease, RNA analysis, 04-103
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 228 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- Aug 2004
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 24 Dec 2007 (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 try to learn more about how small molecule kinase inhibitors work in treating lung cancer. Some early studies have shown that gefitinib, erlotinib and similar drugs are more likely to work if a particular DNA change (also known as a mutation) is found in a protein that is important in lung cancer. This protein is called the epidermal growth factor receptor (EGFR). Since small molecule kinase inhibitors sometimes stop working, we would like to examine your tumor to learn why these medicines are not working as well. Your tumor will be examined for a variety of things including changes in the DNA of the EGFR. We will also sequence parts of the genes for HER2, HER3, HER4, and KRAS, other proteins thought to be important in lung cancer.
Detailed description
The goal of this protocol is to determine mechanisms of resistance to epidermal growth factor (EGFR) tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer (NSCLC). A number of trials have shown small molecule kinase inhibitors to be active agents in the treatment of NSCLC [1]. Clinically these drugs have been noted to produce dramatic but infrequent responses. Mutations in the epidermal growth factor receptor have been shown to correlate with sensitivity to gefitinib and erlotinib[2,3]. However, we know that most patients who have initial responses to EGFR-TKI eventually progress. The mechanism of acquired clinical resistance to these inhibitors in patients incompletely understood.
This is a protocol to study clinical characteristics and biopsy tissue of patients with non-small cell lung cancer who have had previous clinical response to small molecule kinase inhibitors and subsequently experience progression of disease. The tissues and other specimens will be used to carry out laboratory studies to explore the molecular basis of sensitivity and resistance to small molecule kinase inhibitors.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | Other: Tumor core biopsy for RNA isolationThis is a protocol to study tissue specimens to identify changes in tumor DNA in NSCLC patients who have previously responded to therapy and who have subsequently experienced disease progression. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Unresectable or metastatic non-small cell lung cancer (NSCLC)
Key inclusion criteria (4 listed)
- Patients diagnosed with unresectable or metastatic non-small cell lung cancer (NSCLC) and who fulfill the following eligibility criteria will be considered eligible for this study.
- Patient must have previously received treatment with small molecule kinase inhibitors targeting at least, in part, EGFR patients may have received other treatments since treatment with small molecule kinase inhibitors including radiation or chemotherapy)
- Development of disease progression while actively receiving tyrosine kinase inhibitor
- Signed informed consent
Key exclusion criteria (1 listed)
- None
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 |
|---|---|---|
| Tumor core biopsy for RNA isolationRNA isolation will be carried out using approximately 25 mg of gross tissue from these tumor specimens. | Other | 1 |
Primary outcome
To compare EGFR gene sequence in patients upon relapse with EGFR gene sequence prior to treatment with small molecule kinase inhibitors.
Time frame: 2 years
3 secondary outcomes
To identify novel mutations in the tyrosine kinase domain of EGFR in patients with acquired resistance to small molecule kinase inhibitors.
Time frame: 2 years
To more precisely characterize the frequency and clinical implications of T790M in patients with acquired resistance to small molecule kinase inhibitors.
Time frame: 2 years
To identify novel mechanisms of acquired resistance to EGFR small molecule kinase inhibitors.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2016.
- Derived from this study: PubMed 21135146Oxnard GR, Arcila ME, Sima CS, Riely GJ, Chmielecki J, Kris MG, Pao W, Ladanyi M, Miller VA. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res. 2011 Mar 15;17(6):1616-22. doi: 10.1158/1078-0432.CCR-10-2692. Epub 2010 Dec 6.
- Related InfoLink provided by the sponsor.
Related trials for Unresectable or Metastatic 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
RecruitingPhase 3
A Study to Compare Setidegrasib (ASP3082) With Docetaxel, in People With Non-small Cell Lung Cancer With a KRAS G12D Mutation
Non-small Cell Lung Cancer (NSCLC)
Active, not recruitingPhase 3
Trial to Evaluate Acasunlimab and Pembrolizumab Combination Superiority Over Standard of Care Docetaxel in Non-Small Cell Lung Cancer (ABBIL1TY NSCLC-06)
PD-L1-positive, Locally Advanced (Unresectable Stage IIIB/C) or Metastatic NSCLC
RecruitingPhase 3
A Study Comparing TAK-928 With Docetaxel in Adults With Non-Small Cell Lung Cancer
IO Resistant Squamous and Nonsquamous NSCLC
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
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.
Helena Yu, MD principal investigator
Memorial Sloan Kettering Cancer Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Unresectable or Metastatic Non-small Cell Lung Cancer (NSCLC), run by Memorial Sloan Kettering Cancer Center at 5 sites in United States.
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 4 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: finished, as of the sponsor's last update on 4 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To compare EGFR gene sequence in patients upon relapse with EGFR gene sequence prior to treatment with small molecule kinase inhibitors. (time frame: 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 NCT00579683, 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 4 Feb 2016.