Lung CancerMUT-ONCNCT06081270
Prospective Study on Resistance-associated Mutations in Metastatic Lung Cancer
An observational study of Lung Cancer, run by University of Milano Bicocca at 1 site in Italy.
Trial summary
This single-centre prospective study is aimed at analysing, by means of liquid biopsy with next generation sequencing analysis on circulating tumor DNA, resistance mutations arising during therapy with selective inhibitors in patients with RTK-positive NSCLC or with mutations in the Ras/MAPK (mitogen-activated protein… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Cancer
- What is being tested?
- Liquid biopsy
- Type of treatment
- Injection or infusion
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 12 Dec 2021to 31 Dec 2024
- 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: Twenty patients will be enrolled in the study
Who may be able to join
- Over 18 years of age.
- Histological diagnosis of inoperable metastatic or locally advanced lung cancer.
- Positivity for ALK, ROS1, MET, RET (Rearranged during transfection), NTRK (NEUROTROPHIC TYROSINE RECEPTOR KINASE) rearrangements, or KRAS (Kirsten rat sarcoma)-G12C (glycine 12 cysteine) or BRAF-V600E (valine 600 glutamate) mutations, detected by validated method (IHC Immunohistochemistry 3+, FISH (fluorescence in situ hybridization) or Next Generation Sequencing).
- Patients undergoing radiological progression according to RECIST 1.1 criteria to treatment with generation I, II or III inhibitors in any line of treatment. Patients may also have been pre-treated with chemotherapy in earlier lines.
- Presence of measurable disease on radiological investigations. Patients with brain metastases, even as a single site of disease, are eligible for the study.
- Informed consent freely given and obtained before the start of the study.
Who cannot join
- Under 18 years of age
- Unconfirmed histological diagnosis
- Absence of rearrangement or mutation of ALK, ROS1, MET, RET, NTRK, KRAS-G12C or BRAF-V600E
- Progression to chemotherapy in the absence of treatment with TKI or RAS or BRAF inhibitor
- Unmeasurable disease
Trial locations and contacts
1 site in 1 country.
Luca Mologni, PhD contact
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS San Gerardo dei Tintori
Monza, MB, 20900
Diego Cortinovis, MD, diegoluigi.cortinovis@irccs-sangerardo.it
Elisa Sala, PhD, +390392333023, onco.noprofit@gmail.com
About this study
Official title: Prospective Study on Resistance-associated Mutations in Metastatic Lung Neoplasm Patients With Alterations in Driver Oncogenes, Except EGFR, Undergoing Treatment With Specific Inhibitors
This single-centre prospective study is aimed at analysing, by means of liquid biopsy with next generation sequencing analysis on circulating tumor DNA, resistance mutations arising during therapy with selective inhibitors in patients with RTK-positive NSCLC or with mutations in the Ras/MAPK (mitogen-activated protein kinase) pathway, treated at the San Gerardo Hospital, Monza.
Read the detailed description
Non-small-cell lung cancer (NSCLC) is a heterogeneous disease that may have several genetic alterations in oncogenes responsible for progression. 30-40% of NSCLC patients carry mutations affecting the Ras/MAPK pathway, while alterations in receptor tyrosine kinases (RTKs) are found in approximately 25-35% of cases. More than half of the latter are in the Epithelial Growth Factor Receptor (EGFR) gene and have been extensively studied. In the remaining cases, several genes are involved, each with lower frequencies, ranging from around 1% to 5%, depending on the studies. Despite the wide availability of inhibitors, progression remains inevitable due to the emergence of drug resistance mechanisms. The mechanisms by which resistance can be established are essentially of three types: amplification of the target gene, activation of other signal translation pathways (by-pass track) and the occurrence of mutations in the tyrosine kinase domain of the target protein. Liquid biopsy with circulating tumour DNA (ctDNA) analysis provides a non-invasive surrogate method to identify somatic mutations by means of a simple blood sample, without risk to the patient. Moreover, liquid biopsy, by collecting ctDNA from different metastatic sites, could better reflect tumour heterogeneity, both spatial and temporal, and could, therefore, constitute a simple method of longitudinal monitoring during treatment, possibly making it possible to identify relapse early before clinical manifestation. This single-centre prospective study is aimed at analysing, by means of liquid biopsy with next generation sequencing analysis on ctDNA, resistance mutations arising during therapy with selective inhibitors in patients with RTK-positive NSCLC or with mutations in the Ras/MAPK pathway, treated at the San Gerardo Hospital, Monza.
- Conditions
- Lung Cancer
- Being tested
- Liquid biopsy
- Keywords
- ALK (anaplastic lymphoma kinase), ROS (ROS proto-oncogene 1), RET (Rearranged during transfection), B-RAF, lung cancer, tyrosine kinase inhibitor
- Medical subject headings
- Lung Neoplasms, Multiple Endocrine Neoplasia Type 2a
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liquid biopsyOther
Blood withdrawal for each patient is performed (i) at the time of treatment initiation with tyrosine kinase inhibitors (TKI); (ii) at the time of the first planned instrumental re-evaluation according to clinical practice regardless of the type of response to the TKI employed (9-12 weeks); (iii) at the time of radiological progression according to RECIST 1 criteria. 1 at computerized tomography scan with contrast or metabolic progression at 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose during TKI therapy; (iv) at the time of the change of therapeutic strategy decided by the investigator when used beyond progression and not coinciding with point iii. The ctDNA is extracted from plasma and analyzed with Illumina sequencing method.
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of mutation during therapy with selective inhibitors
Evaluation of mutations in ALK (anaplastic lymphoma kinase), ROS1 (ROS proto-oncogene 1), RET, NTRK, MET, KRAS (Kirsten rat sarcoma) and BRAF and in a panel of other known oncogenes during therapy with selective inhibitors by the means of liquid biopsy
Measured: At treatment initiation (baseline), up to 12 weeks from treatment initiation, at the date of first documented progression, assessed up to 24 months from treatment initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2023
- Study start12 Dec 2021
- Primary completion30 Apr 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung CancerStudies 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
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Milano Bicocca
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Diego Cortinovis, MD, Principal investigator, Fondazione IRCCS San Gerardo dei Tintori, MonzaLuca Mologni, PhD, Study chair, University of Milano Bicocca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06081270
- Sponsor's protocol ID
- MUT-ONC
- Acronym
- MUT-ONC
- Status last verified
- Oct 2023
- First submitted
- 6 Sep 2023
- Last updated
- 13 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual patient data will be shared upon request
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Study on Resistance-associated Mutations in Metastatic Lung Neoplasm Patients With Alterations in Driver Oncogenes, Except EGFR, Undergoing Treatment With Specific Inhibitors
- ClinicalTrials.gov ID
- NCT06081270
- Acronym / sponsor ID
- MUT-ONC / MUT-ONC
- Conditions
- Lung Cancer
- Keywords
- ALK (anaplastic lymphoma kinase), ROS (ROS proto-oncogene 1), RET (Rearranged during transfection), B-RAF, lung cancer, tyrosine kinase inhibitor
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of Milano BicoccaUniversity, hospital or other
- Study start
- 12 Dec 2021 (actual)
- Primary completion
- 30 Apr 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 13 Oct 2023 (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.
This single-centre prospective study is aimed at analysing, by means of liquid biopsy with next generation sequencing analysis on circulating tumor DNA, resistance mutations arising during therapy with selective inhibitors in patients with RTK-positive NSCLC or with mutations in the Ras/MAPK (mitogen-activated protein kinase) pathway, treated at the San Gerardo Hospital, Monza.
Detailed description
Non-small-cell lung cancer (NSCLC) is a heterogeneous disease that may have several genetic alterations in oncogenes responsible for progression. 30-40% of NSCLC patients carry mutations affecting the Ras/MAPK pathway, while alterations in receptor tyrosine kinases (RTKs) are found in approximately 25-35% of cases. More than half of the latter are in the Epithelial Growth Factor Receptor (EGFR) gene and have been extensively studied. In the remaining cases, several genes are involved, each with lower frequencies, ranging from around 1% to 5%, depending on the studies. Despite the wide availability of inhibitors, progression remains inevitable due to the emergence of drug resistance mechanisms. The mechanisms by which resistance can be established are essentially of three types: amplification of the target gene, activation of other signal translation pathways (by-pass track) and the occurrence of mutations in the tyrosine kinase domain of the target protein. Liquid biopsy with circulating tumour DNA (ctDNA) analysis provides a non-invasive surrogate method to identify somatic mutations by means of a simple blood sample, without risk to the patient. Moreover, liquid biopsy, by collecting ctDNA from different metastatic sites, could better reflect tumour heterogeneity, both spatial and temporal, and could, therefore, constitute a simple method of longitudinal monitoring during treatment, possibly making it possible to identify relapse early before clinical manifestation. This single-centre prospective study is aimed at analysing, by means of liquid biopsy with next generation sequencing analysis on ctDNA, resistance mutations arising during therapy with selective inhibitors in patients with RTK-positive NSCLC or with mutations in the Ras/MAPK pathway, treated at the San Gerardo Hospital, Monza.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Twenty patients will be enrolled in the study
Key inclusion criteria (6 listed)
- Over 18 years of age.
- Histological diagnosis of inoperable metastatic or locally advanced lung cancer.
- Positivity for ALK, ROS1, MET, RET (Rearranged during transfection), NTRK (NEUROTROPHIC TYROSINE RECEPTOR KINASE) rearrangements, or KRAS (Kirsten rat sarcoma)-G12C (glycine 12 cysteine) or BRAF-V600E (valine 600 glutamate) mutations, detected by validated method (IHC Immunohistochemistry 3+, FISH (fluorescence in situ hybridization) or Next Generation Sequencing).
- Patients undergoing radiological progression according to RECIST 1.1 criteria to treatment with generation I, II or III inhibitors in any line of treatment. Patients may also have been pre-treated with chemotherapy in earlier lines.
- Presence of measurable disease on radiological investigations. Patients with brain metastases, even as a single site of disease, are eligible for the study.
Key exclusion criteria (5 listed)
- Under 18 years of age
- Unconfirmed histological diagnosis
- Absence of rearrangement or mutation of ALK, ROS1, MET, RET, NTRK, KRAS-G12C or BRAF-V600E
- Progression to chemotherapy in the absence of treatment with TKI or RAS or BRAF inhibitor
- Unmeasurable disease
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 |
|---|---|---|
| Liquid biopsyBlood withdrawal for each patient is performed (i) at the time of treatment initiation with tyrosine kinase inhibitors (TKI); (ii) at the time of the first planned instrumental re-evaluation according to clinical practice regardless of the type of response to the TKI employed (9-12 weeks); (iii) at the time of radiological progression according to RECIST 1 criteria. 1 at computerized tomography scan with contrast or metabolic progression at 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose during TKI therapy; (iv) at the time of the change of therapeutic strategy decided by the investigator when used beyond progression and not coinciding with point iii. The ctDNA is extracted from plasma and analyzed with Illumina sequencing method. | Other | – |
Primary outcome
Identification of mutation during therapy with selective inhibitors
Time frame: At treatment initiation (baseline), up to 12 weeks from treatment initiation, at the date of first documented progression, assessed up to 24 months from treatment initiation
Evaluation of mutations in ALK (anaplastic lymphoma kinase), ROS1 (ROS proto-oncogene 1), RET, NTRK, MET, KRAS (Kirsten rat sarcoma) and BRAF and in a panel of other known oncogenes during therapy with selective inhibitors by the means of liquid biopsy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2023.
- Individual participant dataSharing planned: Yes. Individual patient data will be shared upon request
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.
Luca Mologni, PhD contact
Diego Cortinovis, MD principal investigator
Fondazione IRCCS San Gerardo dei Tintori, Monza
Luca Mologni, PhD study chair
University of Milano Bicocca
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 Lung Cancer, run by University of Milano Bicocca at 1 site in Italy.
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 6 inclusion and 5 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 13 Oct 2023. 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 Italy. 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 Clinical Trial Administration (+390392333203, onco.noprofit@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of mutation during therapy with selective inhibitors (time frame: At treatment initiation (baseline), up to 12 weeks from treatment initiation, at the date of first documented progression, assessed up to 24 months from treatment initiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Oct 2023.