Clinical nodal staging for rectal cancer tumours in early stages, is today shown to be unreliable and no precise or accurate methods exist. Thus, there is an unmet need for better clinical staging of rectal cancer in early stages. If new imaging techniques for clinical staging of early rectal cancer are developed an opportunity for increased treatment by local excision and decreased unnecessary radical surgery would be possible.
NanoEcho Particle-1 (NEP-1, Ferumoxtran Lyophilisate 20 mg Fe/mL) will be used, in combination with NanoEcho Imaging Device, to enhance the signal in the detection and identification of possible spread of rectal cancer to nearby rectal regional lymph nodes by magnetomotive ultrasound (MMUS) technology.
NEP-1 is an ultrasmall superparamagnetic iron oxide (USPIO)-based contrast agent. It belongs to the specific contrast agents-group, which are specific to reticuloendothelial system (liver, spleen, lymph nodes, bone marrow), mainly represented by iron oxide nanoparticles coated with macromolecules such as dextran in the presence of adjuvants (mineral salts, polyhydric alcohols, etc.). It belongs to the USPIO sub-group (with a mean particle diameter of 30 nm.
The NanoEcho Imaging Device is based on the MMUS technology. It aims to identify possible spread of rectal cancer to nearby rectal regional lymph nodes by visualisation of the movement, generated by the nanoparticles (nTrace).
The iron oxide-based nanoparticles, NEP-1, are administered submucosally at four separate administration sites locally in rectum, close to the suspected tumour area. After some time allowing the particles to spread, the MMUS probe, dressed in a probe cover with ultrasound gel inside, is inserted into the rectum. The nanoparticles are set in motion by a magnetic field, introduced by a rotating magnet located inside the probe. The motion of the tissue, the so-called tissue displacement, is detected with ultrasound and called NanoEcho visualisation of the movement generated by the nanoparticles (nTrace) and is visualised on the screen of the NanoEcho Imaging Device. The higher the concentration of the nanoparticles, the stronger the nTrace signal. Based on the distribution pattern of the particles, the system aims to support the user in distinguishing between healthy and metastatic lymph nodes located nearby the tumour within the rectal region.
Part A In Part A (healthy volunteers) of the trial, NEP-1 will be administered on a single occasion, followed by four MMUS-assessments, in four ascending dose groups of three participants each.
Part B In Part B (rectal cancer patients) of the trial, NEP-1 will be administered on a single occasion, followed by a MMUS assessment in a maximum of ten patients with rectal cancer. The dose level of NanoEcho Particle-1 (Ferumoxtran) to be used and the timepoint for the MMUS assessment will be decided based on Part A.
Willing and able to give written informed consent for participation in the trial.
Healthy male participant, or female participant of non-childbearing potential aged 18 to 50 years, inclusive.
Body mass index (BMI) ≥ 18.5 and ≤ 30.0 kg/m2 at the time of the screening visit.
Medically healthy participant without abnormal clinically significant medical history, physical findings, vital signs, ECG and laboratory values at the time of the screening visit, as judged by the Investigator. (Discussion is encouraged between the Investigator and the Sponsor Medical Representative regarding the clinical relevance of any abnormal laboratory value during the pre dose period).
History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the trial, or influence the results or the participant's ability to participate in the trial.
Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the administration of IMP.
Malignancy within the past 5 years, with the exception of in situ removal of basal cell carcinoma.
Any planned major surgery within the duration of the trial.
Single group
Iron oxide nanoparticles
DrugSubmucosal injection of nanoparticles in rectum, 28 mg Fe (7 mg Fe/mL)
Rectal Magnetomotoric ultrasound (MMUS)
DeviceMMUS examination of lymphnodes in rectum
Iron oxide nanoparticles
DrugSubmucosal injection in rectum 56 mg Fe (3,5 mg Fe/mL)
Iron oxide nanoparticles
DrugSubmucosal injection in rectum : 56 mg Fe (14 mg Fe/mL)
Iron oxide nanoparticles
DrugSubmucosal injection in rectum 112 mg Fe (14 mg Fe/mL)
Part A: Normalised average nTrace value for all lymph nodes at all timepoints
Dose-response curve and Time-response curve for normalised average nTrace value. nTrace value is NanoEcho visualisation of the movement generated by the nanoparticles
Part B, Normalised average nTrace value for all lymph nodes
Part A. Size of lymph nodes with and without detectable nTrace in Healthy Volunteers
At what size of lymph nodes is (i) lymph nodes detectable (B mode) but no nTrace detectable in lymph nodes? (ii) nTrace detectable in lymph nodes? (iii) nTrace showing an even distribution in lymph nodes?
Part A, Frequency, seriousness, and intensity of adverse events (AEs) for the IMP and the medical device.
Part A. User experience
Result of user experience questionnaire
Part B. Number of lymph nodes detected by NanoEcho diagnostic method compared to historic MRI data per section and overall
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