Non-small Cell Lung CarcinomaEVIDENCENCT02273271
Evaluation of FLT-PET and DWI-MRI in Patients With NSCLC Treated With a Platinum-based Doublet as Preoperative Chemo
A study testing 18F-FLT-PET/CT and DWI-MRI in people with Non-small Cell Lung Carcinoma, run by European Organisation for Research and Treatment of Cancer - EORTC at 2 sites in 2 countries.
Trial summary
The purpose of the study is to qualify, independently, tumor cell proliferation by 3'-Deoxy-3'-[18F]Fluorothymidine (FLT) -Positron Emission Tomography , and cell death by Diffusion Weighted Imaging (DWI) -Magnetic Resonance Imaging (MRI) compared to pathological quantification (% of viable tumor cells) of the primary… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Carcinoma
- What is being tested?
- 18F-FLT-PET/CT and DWI-MRI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Oct 2015to Feb 2017
- Phase
- Interventional
- 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
Who may be able to join
- Age ≥ 18 years
- WHO performance status 0-1 (Appendix C)
- Histologically or cytological confirmed clinical stage II-IIIA non-small cell lung carcinoma (NSCLC), according to 7th TNM classification (Appendix D) (NOTE: patients with resectable N2 disease are also eligible)
- Baseline standard imaging assessment \& staging should be performed within 6 weeks prior to planned treatment start.
- Patients must be candidate for curative intent surgery, and must be expected to complete the treatment.
- ♦♦ Adequate hematology and biochemical investigations, (should be done maximum 6 weeks before treatment starts)
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- Normal bone marrow function based on routine blood samples, i.e. neutrophils ≥ 1.5 x 109/L, platelets ≥ 75 x 109/L, hemoglobin ≥ 10.0 g/dL
- Normal kidney function creatinine clearance ≥ 60 mL/min,
- Normal liver function assessed by routine laboratory examinations, i.e. bilirubin < 1.5 x upper limit of normal (ULN), ALT< 3 x ULN
- Patients must not have any contraindication for 18F-FLT-PET/CT or MRI procedures.
- Patient primary lung tumor larger than 20 mm in diameter (measured by diagnostic CT or MRI).
- Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test before trial registration.
- Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last study procedure. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
- Female subjects who are breast feeding should discontinue nursing before trial registration.
- Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.
Who cannot join
- Prior or current anticancer treatment for NSCLC, pre-operative therapy will include only chemotherapeutic drugs (pemetrexed is contraindicated), no other biological, targeted or radiotherapy is allowed
- Treatment with any investigational drug substance within 4 weeks prior to registration.
- Other malignancies in the 3 years prior to study entry with the exception of surgically cured carcinoma in situ of the cervix, in situ breast cancer, incidental finding of stage T1a or T1b prostate cancer, and basal/squamous cell carcinoma of the skin
- Evidence of any medical condition which would impair the ability of the patient to participate in the trial or might preclude therapy with chemotherapeutic drugs according to routine medical practice (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease, known dihydropyrimidine dehydrogenase deficiency, active infection, uncontrolled diabetes mellitus; uncontrolled arterial hypertension, history of unstable myocardial infarction)
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Italy1 site, 1 recruiting
- Recruiting
Istituto Clinico Humanitas
Milan, 20089
Arturo Chiti, Medical doctor, +39 02 8224 6621, arturo.chiti@hunimed.eu
Arturo Chiti, MD
United Kingdom1 site, 1 recruiting
- Recruiting
Royal Marsden Hospital - Sutton, Surrey
Sutton
Nandita Desouza, MD, +44 2086613289, nandita.desouza@icr.ac.uk
Nandita Desouza, MD
About this study
Official title: Evaluation of 3'-Deoxy-3'-[18F]Fluorothymidine -PET and Diffusion Weighted Imaging -MRI in Patients With Early Stage Non-small Cell Lung Cancer Treated With a Platinum-based Doublet as Preoperative Chemotherapy
The purpose of the study is to qualify, independently, tumor cell proliferation by 3'-Deoxy-3'-[18F]Fluorothymidine (FLT) -Positron Emission Tomography , and cell death by Diffusion Weighted Imaging (DWI) -Magnetic Resonance Imaging (MRI) compared to pathological quantification (% of viable tumor cells) of the primary tumor after pre-operative chemotherapy in patients with operable Non Small Cell Lung Cancer (NSCLC).
Read the detailed description
This is a prospective, multicenter, single-arm imaging trial. Patients with NSCLC will undergo 18F-FLT-PET/CT and DWI-MRI scans on three separate occasions: at baseline, at 14 days (maximum +/- 1 days deviation is acceptable) after first administration of chemotherapy and finally after up to 4 cycles of chemotherapy, and then followed by surgery. The quantification of 18F-FLT SUV and ADC will be measured to assess tumor characteristics and response to therapy.
Patients will be first registered into the EORTC system after signing the informed consent form. The site will have to complete all the study related procedures within 6 weeks prior to treatment and all eligibility criteria should be met before the patient can be enrolled into the study.
Both 18F-FLT-PET/CT and DWI-MRI will be assessed independently in this trial. Therefore the overall type I error of 0.1 will be split by two in order to test independently each imaging biomarker with a one-sided type I error of 0.05. In order to demonstrate with 95% confidence interval (one sided) that the correlation between the imaging biomarker change and the pathological response is > 0.5 (H0: rho ≤ 0.5) with 90% power if the true correlation is 0.8 (H1: rho > 0.5), 31 lesions are needed. As, in this population, patients only have the primary tumor, 31 eligible and evaluable patients will be needed for each primary endpoint.
If all included patients have both 18F-FLT-PET/CT and DWI-MRI then 31 eligible and evaluable patients will be enough. If some patients have only one type of scans (18F-FLT-PET/CT or DWI-MRI), the sample size would need to be adapted to have 31 patients with each type of scans.
In addition, the total number of patients to be registered may be increased to 40 patients for each primary endpoint to take into account some screening failure.
For the primary analysis of correlation between relative change in imaging biomarkers (18F-FLT-SUV or ADC) and pathological quantification, the correlation coefficient will be reported using a one-sided 95% confidence interval, and tested as a one-sided comparison to the null hypothesis (H0: ρ ≤ 0.5). All secondary objectives to correlate preoperative imaging biomarkers and IHC biological markers or tumor volume will use the same analysis as cited above with 99% confidence intervals. All measures will be analyzed in a random effect ANOVA model allowing for within center-variability.
Quality assurance is planned for the control of data consistency, on-site monitoring, audits, and quality assurance in pathological response assessment and in imaging.
- Conditions
- Non-small Cell Lung Carcinoma
- Being tested
- 18F-FLT-PET/CT and DWI-MRI
- Keywords
- FLT-PET, DWI-MRI
- 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.
18F-FLT-PET/CT and DWI-MRIOther
Patients with NSCLC will undergo 18F-FLT-PET/CT and DWI-MRI scans on three separate occasions. Dedicated in-house developed software will be used to quantify 18F-FLT SUV and ADC to assess tumor characteristics and response to therapy.
| Study group | Role | What they receive |
|---|---|---|
| Imaging arm | Experimental | 18F-FLT-PET/CT and DWI-MRI scans at baseline, at 14 days after first administration of chemotherapy and after up to 4 cycles of chemotherapy Receives: Other: 18F-FLT-PET/CT and DWI-MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Apparent Diffusion Coefficient (ADC) change
Percentage of Apparent Diffusion Coefficient (ADC) change at day 14 relative to baseline
Measured: day 14 relative to baseline
Percentage of FLT uptake change
Percentage of FLT uptake change at day 14 relative to baseline
Measured: day 14 relative to baseline
Pathological quantification (% viable residual tumor cells)
participants will receive chemotherapy for up to 12 weeks (4 cycles) and followed by surgery (with an expected surgical preparation of 2-4 weeks)
Measured: in average at week 16 from baseline
Secondary outcomes (5)
Pre-operative (post-treatment) ADC measurement
participants will receive chemotherapy for up to 12 weeks (4 cycles) and performed the DWI-MRI scan within one week prior to the surgery
Measured: in average at week 15 from baseline
Pre-operative (post-treatment) FLT uptake measurement
participants will receive chemotherapy for up to 12 weeks (4 cycles) and performed the FLT-PET scan within one week prior to the surgery
Measured: in average at week 15 from baseline
Tumor volume (baseline, day 14 and post-treatment)
Measured: baseline, day 14 and post-treatment
Immunohistochemistry (IHC) cell proliferation marker Ki-67
Immunohistochemistry (IHC) cell proliferation marker Ki-67-index in diagnostic biopsy samples (if available) and surgical specimens.
Measured: 1y
Metabolic change from FDG-PET (if available)
standard imaging per routine practice
Measured: in average at week 9 from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2014 (estimated)
- Study startOct 2015
- Primary completionDec 2016 (estimated)
- Study completionFeb 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung CarcinomaStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (estimated)
Sponsor and investigators
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Nandita deSouza, Principal investigator, Royal Marsden Hospital - Sutton, SurreySanjay Popat, Study chair, Royal Marsden Hospital - Chelsea, London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02273271
- Sponsor's protocol ID
- EORTC-1217
- Acronym
- EVIDENCE
- Status last verified
- Oct 2015
- First submitted
- 16 Oct 2014
- Last updated
- 30 Oct 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of 3'-Deoxy-3'-[18F]Fluorothymidine -PET and Diffusion Weighted Imaging -MRI in Patients With Early Stage Non-small Cell Lung Cancer Treated With a Platinum-based Doublet as Preoperative Chemotherapy
- ClinicalTrials.gov ID
- NCT02273271
- Acronym / sponsor ID
- EVIDENCE / EORTC-1217
- Conditions
- Non-small Cell Lung Carcinoma
- Keywords
- FLT-PET, DWI-MRI
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 31 participants (estimated)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Study start
- Oct 2015
- Primary completion
- Dec 2016 (estimated)
- Study completion
- Feb 2017 (estimated)
- First posted
- 23 Oct 2014 (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 the study is to qualify, independently, tumor cell proliferation by 3'-Deoxy-3'-[18F]Fluorothymidine (FLT) -Positron Emission Tomography , and cell death by Diffusion Weighted Imaging (DWI) -Magnetic Resonance Imaging (MRI) compared to pathological quantification (% of viable tumor cells) of the primary tumor after pre-operative chemotherapy in patients with operable Non Small Cell Lung Cancer (NSCLC).
Detailed description
This is a prospective, multicenter, single-arm imaging trial. Patients with NSCLC will undergo 18F-FLT-PET/CT and DWI-MRI scans on three separate occasions: at baseline, at 14 days (maximum +/- 1 days deviation is acceptable) after first administration of chemotherapy and finally after up to 4 cycles of chemotherapy, and then followed by surgery. The quantification of 18F-FLT SUV and ADC will be measured to assess tumor characteristics and response to therapy.
Patients will be first registered into the EORTC system after signing the informed consent form. The site will have to complete all the study related procedures within 6 weeks prior to treatment and all eligibility criteria should be met before the patient can be enrolled into the study.
Both 18F-FLT-PET/CT and DWI-MRI will be assessed independently in this trial. Therefore the overall type I error of 0.1 will be split by two in order to test independently each imaging biomarker with a one-sided type I error of 0.05. In order to demonstrate with 95% confidence interval (one sided) that the correlation between the imaging biomarker change and the pathological response is > 0.5 (H0: rho ≤ 0.5) with 90% power if the true correlation is 0.8 (H1: rho > 0.5), 31 lesions are needed. As, in this population, patients only have the primary tumor, 31 eligible and evaluable patients will be needed for each primary endpoint.
If all included patients have both 18F-FLT-PET/CT and DWI-MRI then 31 eligible and evaluable patients will be enough. If some patients have only one type of scans (18F-FLT-PET/CT or DWI-MRI), the sample size would need to be adapted to have 31 patients with each type of scans.
In addition, the total number of patients to be registered may be increased to 40 patients for each primary endpoint to take into account some screening failure.
For the primary analysis of correlation between relative change in imaging biomarkers (18F-FLT-SUV or ADC) and pathological quantification, the correlation coefficient will be reported using a one-sided 95% confidence interval, and tested as a one-sided comparison to the null hypothesis (H0: ρ ≤ 0.5). All secondary objectives to correlate preoperative imaging biomarkers and IHC biological markers or tumor volume will use the same analysis as cited above with 99% confidence intervals. All measures will be analyzed in a random effect ANOVA model allowing for within center-variability.
Quality assurance is planned for the control of data consistency, on-site monitoring, audits, and quality assurance in pathological response assessment and in imaging.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Imaging arm | Experimental | Other: 18F-FLT-PET/CT and DWI-MRI18F-FLT-PET/CT and DWI-MRI scans at baseline, at 14 days after first administration of chemotherapy and after up to 4 cycles of chemotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age ≥ 18 years
- WHO performance status 0-1 (Appendix C)
- Histologically or cytological confirmed clinical stage II-IIIA non-small cell lung carcinoma (NSCLC), according to 7th TNM classification (Appendix D) (NOTE: patients with resectable N2 disease are also eligible)
- Baseline standard imaging assessment \& staging should be performed within 6 weeks prior to planned treatment start.
- Patients must be candidate for curative intent surgery, and must be expected to complete the treatment.
Key exclusion criteria (5 listed)
- Prior or current anticancer treatment for NSCLC, pre-operative therapy will include only chemotherapeutic drugs (pemetrexed is contraindicated), no other biological, targeted or radiotherapy is allowed
- Treatment with any investigational drug substance within 4 weeks prior to registration.
- Other malignancies in the 3 years prior to study entry with the exception of surgically cured carcinoma in situ of the cervix, in situ breast cancer, incidental finding of stage T1a or T1b prostate cancer, and basal/squamous cell carcinoma of the skin
- Evidence of any medical condition which would impair the ability of the patient to participate in the trial or might preclude therapy with chemotherapeutic drugs according to routine medical practice (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease, known dihydropyrimidine dehydrogenase deficiency, active infection, uncontrolled diabetes mellitus; uncontrolled arterial hypertension, history of unstable myocardial infarction)
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before randomization in the trial.
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 |
|---|---|---|
| 18F-FLT-PET/CT and DWI-MRIPatients with NSCLC will undergo 18F-FLT-PET/CT and DWI-MRI scans on three separate occasions. Dedicated in-house developed software will be used to quantify 18F-FLT SUV and ADC to assess tumor characteristics and response to therapy. | Other | Imaging arm |
Primary outcome
Percentage of Apparent Diffusion Coefficient (ADC) change
Time frame: day 14 relative to baseline
Percentage of Apparent Diffusion Coefficient (ADC) change at day 14 relative to baseline
Percentage of FLT uptake change
Time frame: day 14 relative to baseline
Percentage of FLT uptake change at day 14 relative to baseline
Pathological quantification (% viable residual tumor cells)
Time frame: in average at week 16 from baseline
participants will receive chemotherapy for up to 12 weeks (4 cycles) and followed by surgery (with an expected surgical preparation of 2-4 weeks)
5 secondary outcomes
Pre-operative (post-treatment) ADC measurement
Time frame: in average at week 15 from baseline
Pre-operative (post-treatment) FLT uptake measurement
Time frame: in average at week 15 from baseline
Tumor volume (baseline, day 14 and post-treatment)
Time frame: baseline, day 14 and post-treatment
Immunohistochemistry (IHC) cell proliferation marker Ki-67
Time frame: 1y
Metabolic change from FDG-PET (if available)
Time frame: in average at week 9 from baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2015.
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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.
Nandita deSouza principal investigator
Royal Marsden Hospital - Sutton, Surrey
Sanjay Popat study chair
Royal Marsden Hospital - Chelsea, London
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 18F-FLT-PET/CT and DWI-MRI in people with Non-small Cell Lung Carcinoma, run by European Organisation for Research and Treatment of Cancer - EORTC at 2 sites in 2 countries.
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 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 30 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy, United Kingdom. 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 Oussama Karroum (003227741523, oussama.karroum@eortc.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Apparent Diffusion Coefficient (ADC) change (time frame: day 14 relative to baseline). The study lists 3 primary outcomes in all. 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 30 Oct 2015.