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Squamous Cell Carcinoma of Head and NeckSEMIRAHNNCT04688528

Dose De-escalation and Sentinel LN Mapping Driven Radiotherapy of Contralateral Neck in Ipsilateral Node Positive HNSCC

A study testing Dose de-escalation and / or Volume de-escalation in people with Squamous Cell Carcinoma of Head and Neck, run by Universitaire Ziekenhuizen KU Leuven at 10 sites in Belgium.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The study involves head and neck squamous cell carcinomas (HNSCC) of the oral cavity, oropharynx, larynx or hypopharynx with positive nodes on only one side of the neck and no distant metastasis treated by primary (chemo)radiotherapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Squamous Cell Carcinoma of Head and Neck
What is being tested?
Dose de-escalation and / or Volume de-escalation
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
147 participants
Where
10 sitesBelgium
Study dates
10 Jun 2021to Jan 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

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

  • Written informed consent given according to ICH/GCP and national/local regulations must be obtained prior to any screening procedures.
  • World Health Organization (WHO) performance status 0-1.
  • Age ≥ 18 years.
  • Patients with a pathologically proven invasive HNSCC, including oral cavity, oropharynx (independently of HPV status), larynx or hypopharynx.
  • Decision by Multidisciplinary Tumor Board of primary treatment with radical radiotherapy with or without concurrent chemotherapy (according to the local guidelines).
  • Baseline imaging of the neck:
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  • ≤ 2.5 mm slices CT with iodine injection (independently or during the FDG-PET/CT examination IF acquired in normal diagnostic conditions, i.e. arms along the thorax with diagnostic quality);
  • MRI not mandatory but allowed, performed according to centres guidelines;
  • FDG-PET/CT.
  • Tumor characteristics:
  • cT-classification (8th TNM staging): T1(except T1 of glottis)-T4a (or, for p16+ oropharyngeal tumors classified cT4, if criteria are compatible with cT4a-stage of p16- tumors).
  • cN-classification (8th TNM staging), as assessed by iodine contrasted CT (or MRI) and FDG-PET:
  • i. mandatorily cN0 contralaterally to the primary tumor (or on one side of the neck for midline primary tumors):
  • 1. smallest diameter < 5 mm in retropharyngeal level (VIIa);
  • 2. smallest diameter of Küttner node (level IIa) < 12 mm;
  • 3. smallest diameter < 10 mm or sum of smallest and largest diameters < 17 mm in any other level;
  • 4. no central necrosis ;
  • 5. maximal standardized uptake value (SUVmax) ≤ 2.2;
  • 6. in dubious cases (typically 2.2 < SUVmax < 4.5 and inconclusive CT or MRI), US-guided FNAC may be required to exclude positive node contralaterally.
  • ii. ipsilaterally positive (if any of the above mentioned criteria is met), i.e. cN1, cN2a, cN2b, ipsilateral cN3b; or cN1 for oropharyngeal p16+ tumors.
  • No distant metastasis.

Who cannot join

  • Patient has history of:
  • radiotherapy or surgery in the neck with potential impact on lymphatic drainage ("violated neck");
  • cancer in the last five years (excluding skin basal cell carcinoma, in situ cervix carcinoma and T1 of glottis or lip, completely chirurgically resected (R0) without intervention disturbing cervical lymph drainage);
  • Absolute contra-indication to iodine contrast injection, even after proper cortisone and cetirizine pre-medication.
  • HNSCC from nose, sinuses, oesophagus, salivary glands or nasopharynx.
  • Non-HNSCC histology.
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  • Positive contralateral neck by node size or positive US-FNAC in dubious nodes.
  • Synchronous second malignancy.
  • Distant metastasis.
  • Tumor crossing the midline without contralateral mapping after 99mTc-nanocolloïd injection.
  • Tumor too large to be safely injected, as deemed by the surgeon. In case of doubt, contact may always be taken with the national coordinating investigator to discuss the situation and take a final decision.
  • Any psychological disorder or familial, sociological or geographical condition which, in the investigator's opinion, might jeopardise participant's safety or compliance with the protocol.
  • Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method.
  • Highly effective methods of birth control are defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatments) or vasectomised partner.

Trial locations and contacts

10 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Jean-François Daisne, MD, PhD contact

+32-16-34-76-00

jean-francois.daisne@uzleuven.be

Chris Bruyninckx, BA contact

+32-16-34-76-00

chris.bruyninckx@uzleuven.be

10 sites in 1 country

Belgium10 sites, 10 recruiting

  • OLV Aalst

    Aalst, 9300

    Laurien De Waele, laurien.de.waele@olvz-aalst.be

    Sofie Tombeur, sofie.tombeur@olvz-aalst.be

    Recruiting

  • UCL Saint-Luc

    Brussels, 1200

    Eléonore Longton, eleonore.longton@saintluc.uclouvain.be

    Eléonore Longton

    Recruiting

  • Institute Jules Bordet

    Brussels

    Clémence Al Wardi, clemence.alwardi@bordet.be

    Dirk Van Gestel, MD, PhD

    Recruiting

  • ZOL

    Genk, Limburg, 3600

    Liesbeth Raymakers, studies.radiotherapy@jessazh.be

    Elien Scherpenberg, studies.radiotherapy@jessazh.be

    Recruiting

  • University Hospital Gent

    Ghent

    Frederic Duprez, frederic.duprez@uzgent.be

    Frederic Duprez, MD, PhD

    Recruiting

  • Jessa Ziekenhuis

    Hasselt, Limburg, 3500

    Liesbeth Raymakers, studies.radiotherapy@jessazh.be

    Elien Scherpenberg, studies.radiotherapy@jessazh.be

    Recruiting

  • Universitaire Ziekenhuizen Leuven

    Leuven, 3000

    Chris Bruyninckx, chris.bruyninckx@uzleuven.be

    Rita Aerts, rita.aerts@uzleuven.be

    Recruiting

  • AZ Sint-Maarten

    Mechelen, 2800

    Julie van der Veen, Julie.van.der.Veen@emmaus.be

    Julie van der Veen

    Recruiting

  • CHU-UCL Namur

    Namur

    Monique Gilsoul, monique.gilsoul@chuuclnamur.uclouvain.be

    Stéphanie Deheneffe, MD

    Recruiting

  • AZ Turnhout

    Turnhout, 2300

    Nel Bovin, Nel.Bovin@azturnhout.be

    Michel Martens

    Recruiting

Other trials in Belgium

About this study

Official title: A Prospective Randomized Phase 2 Study of Dose and Volume De-escalation Radiotherapy With Sentinel Lymph Nodes Mapping for Contralateral Irradiation in Unilaterally Node Positive Head and Neck Squamous Cell Carcinomas (SEMIRAHN)

The study involves head and neck squamous cell carcinomas (HNSCC) of the oral cavity, oropharynx, larynx or hypopharynx with positive nodes on only one side of the neck and no distant metastasis treated by primary (chemo)radiotherapy.

The elective node irradiation on the contralateral side is not always mandatory and the dose may be too high. In this study, we evaluate two strategies: the impact of sentinel lymph node mapping to tailor the volumes to irradiate and the dose reduction.

Read the detailed description

The risk of lymph drainage to the contralateral side of the neck is limited to maximum 50% of the patients. Moreover, the risk of occult metastases lies between 20 and 40%. As a consequence, the rule of irradiating the contralateral neck with a prophylactic intent ("elective nodal irradiation") in nearly all HNSCC patients roughly doubles the irradiated volume and, hence, increases the risk of developing more frequent and more severe acute and late side effects. The use of sentinel lymph node mapping to assess the contralateral side of the neck should help to determine the individual drainage to the contralateral side of the neck and, in case of drainage, determine which nodes need to be irradiated. The ultimate goal is to reduce the volume irradiated at prophylactic dose to decrease the risk of severe late side effects (volume de-escalation strategy). This strategy is proposed based on the recent completion of a similar study led by the coordinating investigator, together with the head and neck team of the CHU-UCL-Namur, in HNSCC patients without macroscopic nodes in the neck and treated with (chemo)radiotherapy. It was shown that sentinel lymph node mapping helped to safely individualize and de-escalate the elective nodal irradiation volume and significantly reduce the risk of severe late side effects. Anyway, it is unknown if the whole sub-region of the neck containing the sentinel lymph node(s) or the node(s) only should be defined as target volume.

Moreover, the dose used nowadays for elective nodal irradiation, i.e. 50 Gy in fractions of 2 Gy or biologically equivalent, dates back from the 70's. Many arguments (a.o. our better capacity to stage the neck with 3D imaging and the use of concomitant chemotherapy in the majority of node-positive HNSCC) are in favour of dose de-escalation. A multicentric randomized study performed in 100 HNSCC recently showed that the elective dose could be reduced to 40 Gy in fractions of 2 Gy or biologically equivalent, helping to reduce the risk of late dysphagia at 6 months post-radiotherapy. Confirmatory studies need to be performed on larger groups of patients.

The primary aim is to evaluate contralateral regional control (cRC) rate at 2 years in head and neck squamous cell carcinomas (HNSCC) of the oral cavity, oropharynx, larynx or hypopharynx with positive nodes on only one side of the neck and no distant metastasis treated by (chemo)radiotherapy applying a dose- and/or volume de-escalation.

Being tested
Dose de-escalation and / or Volume de-escalation
Keywords
HNSCC, Dose and Volume de-escalation in radiotherapy, sentinel lymph nodes mapping
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dose de-escalation and / or Volume de-escalationRadiation

    The dose de-escalation and/or volume de-escalation strategy will be individually adapted in function of the draining pattern of sentinel lymph nodes on the contralateral side of the neck.

Study groups in NCT04688528
Study groupRoleWhat they receive
Arm A: Unilateral RTExperimentalIf SPECT/CT shows ipsilateral drainage and the tumor does not cross the midline, the subject will automatically be assigned to Arm A, and will receive ipsilateral Radiotherapy with reduced prophylactic dose outside of the macroscopically involved nodes. The contralateral side of the neck will be spared according to the absence of sentinel lymph node drainage.
Receives: Radiation: Dose de-escalation and / or Volume de-escalation
Arm B: Whole levelExperimentalIf SPECT/CT shows contralateral drainage, the subject will be randomized between 'Whole level' and 'SLN alone'. Arm B 'Whole Level': on the contralateral side of the neck, the whole level(s) containing the draining sentinel lymph node(s) will be irradiated at the reduced prophylactic dose. The ipsilateral side of the neck will be irradiated conform to arm A.
Receives: Radiation: Dose de-escalation and / or Volume de-escalation
Arm C: SLN aloneExperimentalIf SPECT/CT shows contralateral drainage, the subject will be randomized between 'Whole level' and 'SLN alone'. Arm C 'SLN alone': on the contralateral side of the neck, only the sentinel node(s) will be irradiated at the reduced prophylactic dose. The ipsilateral side of the neck will be irradiated conform to arm A.
Receives: Radiation: Dose de-escalation and / or Volume de-escalation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Contralateral regional control (cRC) rate at 2 years

    The rate of tumor control in the draining nodal regions of the neck.

    Measured: From baseline to 2 years after radiotherapy

Secondary outcomes (7)

  1. Questionnaire assessing the quality of life of patients with head and neck cancer

    Measured by the EORTC QLQ-H\&N35 questionnaire.

    Measured: From baseline to every 2 months in the first year and every 3 months in the second year after radiotherapy.

  2. Questionnaire assessing the quality of life of cancer patients.

    Measured by the EORTC QOL-C30 (version3) questionnaire.

    Measured: From baseline to every 2 months in the first year and every 3 months in the second year after radiotherapy.

  3. Normal tissue complication probability (NTCP) gain estimation

    Estimation of the difference in risk of complications for xerostomia, dysphagia and hypothyroidism according to validated NTCP models.

    Measured: Time from RT up to 2 years after RT.

  4. Local Control

    Loco-regional control (LRC)

    Measured: Time from RT until local progression or death whichever comes first, up to 2 years after RT.

  5. Survival

    Cancer specific survival

    Measured: Time from RT until the occurrence of a new tumor or death whichever comes first, up to 2 years after RT.

  6. Survival

    Overall survival

    Measured: Time from RT until death from any cause

  7. Radiotherapy induced toxicity

    Acute and Late Toxicity Scoring

    Measured: Time from start of RT up to 2 years after RT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Dec 2020
  2. Study start10 Jun 2021
  3. Primary completionJan 2027 (estimated)
  4. Study completionJan 2027 (estimated)

Resources

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
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
147 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04688528
Sponsor's protocol ID
S63909
Other IDs
FAF-C/2018/1266
Acronym
SEMIRAHN
Status last verified
Jun 2024
First submitted
18 Dec 2020
Last updated
1 Jul 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Daisne JF, Installe J, Bihin B, Laloux M, Vander Borght T, Mathieu I, Lawson G. SPECT/CT lymphoscintigraphy of sentinel node(s) for superselective prophylactic irradiation of the neck in cN0 head and neck cancer patients: a prospective phase I feasibility study. Radiat Oncol. 2014 May 28;9:121. doi: 10.1186/1748-717X-9-121.

    PubMed 24885222

  • Longton E, Lawson G, Bihin B, Mathieu I, Hanin FX, Deheneffe S, Vander Borght T, Laloux M, Daisne JF. Individualized Prophylactic Neck Irradiation in Patients with cN0 Head and Neck Cancer Based on Sentinel Lymph Node(s) Identification: Definitive Results of a Prospective Phase 1-2 Study. Int J Radiat Oncol Biol Phys. 2020 Jul 15;107(4):652-661. doi: 10.1016/j.ijrobp.2020.03.021. Epub 2020 Apr 12.

    PubMed 32294522

Questions about this trial

What is this clinical trial studying?

A study testing Dose de-escalation and / or Volume de-escalation in people with Squamous Cell Carcinoma of Head and Neck, run by Universitaire Ziekenhuizen KU Leuven at 10 sites in Belgium.

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 21 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 1 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in Belgium. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jean-François Daisne, MD, PhD (+32-16-34-76-00, jean-francois.daisne@uzleuven.be), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Contralateral regional control (cRC) rate at 2 years (time frame: From baseline to 2 years after radiotherapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04688528, which also lists 2 linked publications.

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 1 Jul 2024.

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