Primary objective: The primary objective of this study is to compare the preoperative radiotracer kinetics (rate of injection site clearance and rate of SLN uptake) for Lymphoseek and 99mTc-Nanocoll. Secondary objectives: * To compare the number of…
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Source
Brief title
Condition
- Head and neck therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The most important parameter of this pilot study is to compare the preoperative
radiotracer kinetics (rate of injection site clearance and rate of SLN uptake)
for Lymphoseek and 99mTc-Nanocoll.
Secondary outcome
Secondary objectives:
* To compare the number of lymphoscintigraphically detected SLNs identified by
Lymphoseek and 99mTc-Nanocoll on a per-subject basis.
* To compare differences in the ratio of counts between Lymphoseek and
99mTc-Nanocoll for the hottest SLN relative to the primary peritumoral
injection site.
* To compare patient pain tolerance (i.e., patient*s perceived level of
discomfort) at the injection site for Lymphoseek and 99mTc-Nanocoll.
* To compare pathologic assessment (presence or absence of metastasis) of the
excised lymph node(s) identified by Lymphoseek and 99mTc-Nanocoll on a
per-subject basis.
* To compare the number of nodes localized at the early scan (0-4 hour) with
the number of nodes localized on the late scan (20-26 hour).
* Observing contralateral drainage patterns in lateralized tumors and compare
these patterns between Lymphoseek and 99mTc-Nanocoll, especially in case of a
positive sentinel node
Background summary
The sentinel lymph node (SLN) procedure is a diagnostic staging procedure that
is applied in a variety of tumor types, including head and neck squamous cell
carcinoma (HNSCC). The procedure aims to identify the first draining lymph
node(s), the SLN(s), which is most likely to harbor metastases. The
histopathologic status of the SN should reflect the histopathologic status of
the rest of the nodal basin, and additional treatment of the nodal basin (e.g.,
surgery) should be performed in case of metastatic involvement of the SLN. A
negative SLN, however, would justify a wait and see policy concerning treatment
of the nodal basin. In short, the routine SLN procedure consists of
preoperative peritumoral injections of a 99m-technetium (99mTc)-labeled colloid
followed by lymphoscintigraphy using planar or single photon emission
tomography (SPECT) imaging. Based on the lymphoscintigraphy the position of the
SLN is marked on the skin and intraoperative detection is possible by tumor
injection of blue dye and by using a portable gamma probe (1).
Until now, most data showed that the combined dye and radioactive colloid
approach reliably stages the clinically negative neck (cN0) in early stage oral
cavity carcinoma (2,3,4). However, in floor of mouth (FOM) tumors, detection of
the SLN is more difficult. This is probably due to the short distance between
the primary tumor and the first draining lymph nodes (SLNs), which may be found
in the submandibular region. In these cases, the resolution of the gamma- or
SPECT camera is not always sufficient to visualize the SLN(s). The injection
site (around the primary tumor) produces a large hotspot on lymphoscintigraphy
possibly hiding SLN(s) in the close proximity of the primary tumor (*shine
through* / *overshine*). As a result, second echelon lymph nodes may
erroneously be considered as SLNs. On lymphoscintigraphy it is often difficult
to differentiate hot spots between real sentinel nodes and second echelon
nodes. In clinical practice probably too many lymph nodes are harvested because
some hot spots will actually represent second echelon nodes. Extirpation of
second echelon nodes may induce unnecessary morbidity and risk of complications.
Based on a multivalent strategy, Lymphoseek (99mTc-Tilmanocept) exhibits a high
affinity for a lymphoid-specific receptor, which provides sustained SLN uptake
without distal node accumulation (second echelon nodes).
Due to its rapid clearance from the injection site, rapid uptake and high
retention within the first drainage lymph node (SLN), as well as low uptake by
the remaining (higher echelon) lymph nodes Lymphoseek may be of benefit in
floor of mouth tumors and other head and neck tumors with complex drainage
patterns and close spatial relation to the SLN: better visualization of SLNs
close to the injection site and less hot spots in second echelon nodes.
The aim of the present pilot study is to evaluate the preoperative radiotracer
kinetics of Lymphoseek and 99mTc-Nanocoll in sentinel lymph node biopsy in
early oral cancer patients. This pilot study should be performed before
designing a comparative study with sufficient number of patients to find an
eventual difference in effectiveness between these tracers.
Study objective
Primary objective:
The primary objective of this study is to compare the preoperative radiotracer
kinetics (rate of injection site clearance and rate of SLN uptake) for
Lymphoseek and 99mTc-Nanocoll.
Secondary objectives:
* To compare the number of lymphoscintigraphically detected SLNs identified by
Lymphoseek and 99mTc-Nanocoll on a per-subject basis.
* To compare the number of nodes localized at the scans at 2 time points for
both tracers (0-30 minutes postinjection and 2-4 hours postinjection), to
correlate the number of nodes with the late static scan (20h-26h postinjection)
for the second agent and correlate these findings with the intraoperative
findings.
* To compare differences in the ratio of counts between Lymphoseek and
99mTc-Nanocoll for the hottest SLN relative to the primary peritumoral
injection site.
* To compare patient pain tolerance (i.e., patient*s perceived level of
discomfort) at the injection site for Lymphoseek and 99mTc-Nanocoll.
* To compare pathologic assessment (presence or absence of metastasis) of the
excised lymph node(s) identified by Lymphoseek and 99mTc-Nanocoll on a
per-subject basis.
* To compare the number of nodes localized at the early scan (2-4 hour) with
the number of nodes localized on the late scan (22-26 hour).
* Observing contralateral drainage patterns in lateralized tumors and compare
these patterns between Lymphoseek and 99mTc-Nanocoll, especially in case of a
positive sentinel node
Study design
This pilot study is a within-patient evaluation of radiotracer kinetics of
Lymphoseek and 99mTc-Nanocoll for identification of sentinel lymph nodes in
early stage oral cavity carcinoma.
The patients 1-10 will receive first the peritumoral injections with Lymphoseek
with imaging as routinely done for the sentinel node procedure. 4-11 days
later, the procedure will be performed routinely (so with Nanocoll). After
these patients a team consisting of a nuclear physician, investigator and head
and neck surgeon will evaluate if the farmacokinetics of Lymphoseek result in
lymphoscintigrams which are at least as good as the lymphoscintigrams of
99mTc-Nanocoll. When the imaging is at least as good as Nanocoll, patients
11-20 will receive the tracers in the opposite direction (so first Nanocoll +
imaging, whereafter 4-11 days the SN procedure will be performed with
Lymphoseek as radioactive agent).
Intervention
The intervention consists of the Lymphoseek injection 4-11 days before the
standard procedure in the first 10 patients to compare the imaging between
Lymphoseek and Nanocoll. However, after 10 patients and when the imaging of
Lymphoseek will be considered as least as good as Nanocoll, the next 10
patients will receive the Nanocoll first and 4-11 days later the Lymphoseek as
tracer for the SN procedure. The other aspects of the procedure will be
unmodified.
Study burden and risks
Lymphoseek may identify SLNs more reliable than routinely used Nanocoll. The
information obtained by lymphoscintigraphy may be helpful in harvesting the
sentinel lymph node(s). The extra administration of 0.69mSv of the injection
agent will result in an acceptable radiation burden to the patient, i.e.,
comparable to natural background level. Therefore we conclude the risk is
negligible for this study.
Heidelberglaan 100
Utrecht 3508GA
NL
Heidelberglaan 100
Utrecht 3508GA
NL
Listed location countries
Age
Inclusion criteria
1. The patient has provided written informed consent authorization before participating in the trial.
2. The patient has a diagnosis of primary oral squamous cell carcinoma that is anatomically located in: mucosal lip, buccal mucosa, lower alveolar ridge, upper alveolar ridge, retromolar gingival (retromolar trigone), floor-of-the-mouth, hard palate or oral (mobile) tongue, and is stage T1-T2, N0, M0 (see Appendix 3: TNM Staging).
3. Clinical nodal staging (N0) has been confirmed by negative results from ultrasound guided fine needle aspiration cytology within 30 days of the SLN procedure.
4. The patient is a candidate for transoral excision.
5. Patients with prior malignancy are allowed provided the patient meets both of the following criteria:
* Underwent potentially curative therapy for all prior malignancies and is deemed low risk for recurrence; and
* No malignancy for the past five years (except effectively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix effectively treated with surgery alone or lobular carcinoma in situ of the breast treated with surgery alone), and no evidence of recurrence.
6. The patient is >18 years of age at the time of consent
7. The patient has an ECOG status of Grade 0 * 2 (see Appendix 4: Performance Status Criteria).
Exclusion criteria
1. The patient has a diagnosis of squamous cell carcinoma of the head and neck in the following anatomical areas: non-mobile base of the tongue, oropharynx, nasopharynx, hypopharynx, and larynx.
2. The patient is pregnant or lactating.
3. Patient is incapacitated
4. The patient has clinical or radiological evidence of metastatic cancer to the regional lymph nodes.
5. The patient has a history of neck dissection, or gross injury to the neck that would preclude reasonable surgical dissection for this trial, or radiotherapy to the neck.
6. The patient has had other nuclear imaging studies, including technetium 99m, conducted within 10 days (240 hours) of injection.
7. The patient is actively receiving systemic cytotoxic chemotherapy.
8. The patient is currently participating in another investigational drug trial or participated within 30 days prior to consenting.
9. Patient is on immunosuppressive, anti-monocyte, or immunomodulatory therapy.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-000512-42-NL |
| CCMO | NL58099.041.17 |