|- candidate number||21986|
|- NTR Number||NTR5203|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||20-apr-2015|
|- Secondary IDs||NL46671.029.13 |
|- Public Title||A study of radioactive afatinib, [18F]afatinib, in lung cancer patients, to evaluate its uptake in tumors and its predictive value to identify patients who will respond to afatinib therapy|
|- Scientific Title||Can tumor uptake of [18F]afatinib in NSCLC patients be quantified, and does [18F]afatinib uptake identify patients who will benefit from afatinib therapy ?|
|- hypothesis||the tumor uptake of [18F]afatinib will be able to predict afatinib-sensitive tumors|
|- Healt Condition(s) or Problem(s) studied||Non small cell lung cancer (NSCLC), EGFR mutation|
|- Inclusion criteria||- Age18-70 years |
- Patient is planned to receive afatinib after scanning
- Histologically proven NSCLC, with EGFR mutational status (as determined by high resolution melting and DNA sequencing)
- Life expectancy of at least 12 weeks
- Malignant lesion of at least 1.5 cm diameter within the chest as measured by CT
- Performance status Karnofsky index >60%
- Written informed consent
|- Exclusion criteria||- Claustrophobia
- Pregnant or lactating patients |
- Patients having metal implants in the thorax that could cause an attenuation artefact (e.g. pacemakers)
- Concurrent treatment with experimental drugs
- Anaemia (Hb below lower limit of normal)
- Coumarin therapy
|- mec approval received||yes|
|- multicenter trial||no|
|- planned startdate ||1-mei-2015|
|- planned closingdate||1-mei-2017|
|- Target number of participants||20|
|- Interventions||There will be 4 subsequent steps involving 4, 8 and 8 patients, respectively, in order to find the optimal PET scanning conditions. |
Step 0: Dosimetry. We will follow the published methods for assessing radiation safety of an [18F]-labeled PET traces for first-in-human studies. A single subject will undergo 4 whole-body PET scans using a 74 MBq dose, to test if [18F]afatinib disproportionately accumulates in a single radiosensitive organ. If, as expected, it does not, then the next step will be performed.
Step 1: The first 4 patients will undergo a low dose CT scan, followed by a dynamic [15O]H2O PET scan and thereafter a prolonged (90 + 30 minutes) dynamic [18F]afatinib PET scan. Arterial sampling will be performed. After step 1, kinetic analysis of the prolonged dynamic PET data will be performed to determine the best scanning interval for a whole body static PET scan.
Step 2: The subsequent 8 patients (regardless of the groups they are in) will undergo 2 scanning procedures on subsequent days for determining test-retest repeatability. A low dose CT scan, followed by a dynamic [15O]H2O PET scan and thereafter a 60-min dynamic [18F]afatinib PET scan will be done, followed by a break (duration will be determined by step 1). After this, a low dose CT and a 40-min static [18F]afatinib whole body PET scan will be made. Arterial sampling will be performed. After step 2, a preliminary analysis will be performed to determine the optimal kinetic model, find the corresponding measure of uptake, assess test-retest repeatability, assess whether arterial blood sampling is still needed, and evaluate the validity of simplified parameters (e.g. SUV) obtained with whole body scans.
Step 3: The final 8 patients will only undergo a low dose CT scan, followed by a [15O]H2O dynamic PET scan and thereafter a 60-min dynamic [18F]afatinib PET scan, followed by a break, a low dose CT and a 40-min static [18F]afatinib whole body PET scan. Venous and arterial blood samples will be drawn.
|- Primary outcome||1. To define the optimal pharmacokinetic tracer model for [18F]afatinib.
2. To determine the optimal simplified measure for quantifying tumor [18F]afatinib uptake
3. To assess [18F]afatinib uptake differences between patients (1) with wild type EGFR, (2) EGFR mut+, TKI-resistant EGFR mut+ (3) with and (4) without T790M mutations.
4. To assess whether [18F]afatinib uptake is predictive for tumor response to afatinib in patients with wild type EGFR and EGFR mut+, prior to TKI therapy and after resistance occurs to a 1st generation TKI.
|- Secondary outcome||same as primary|
|- Timepoints||as stated in the intervention section: 3 steps in 2 years|
|- Trial web site|
|- CONTACT FOR PUBLIC QUERIES||MD Iris Bahce|
|- CONTACT for SCIENTIFIC QUERIES||MD Iris Bahce|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|- Brief summary|
|- Main changes (audit trail)|
|- RECORD||20-apr-2015 - 25-jul-2015|