NAVIGATORR
Overview
- Study title: Multiparametric, image-guided intraoperative navigation to guide surgical resection and postoperative radiotherapy in patients with head and neck tumours
- Study design: Prospective multicentre feasibility study
- Study participants: Adult patients with a resectable carcinoma of the midface, maxilla, or skull base, and a high likelihood of requiring postoperative radiotherapy
- Study objective: NCT05671458
Study status: currently recruiting
The NAVIGATORR study (Multiparametric, imageguided intraoperative navigation for guidance of surgical resection and postoperative radiotherapy in patients with head and neck tumours) is a prospective feasibility study. It enrols adult patients with resectable carcinoma of the midface, maxilla, or skull base. Patients with the following histological subtypes are eligible to participate:
- Oral squamous cell carcinoma (OSCC)
- Adenoid cystic carcinoma of the salivary glands (ACC)
- Mucoepidermoid carcinoma of the salivary glands (MEC)
- Adenocarcinoma (AC)
Oral squamous cell carcinomas (OSCC), along with the less common salivary gland tumours, represent the vast majority of tumours of the head and neck region. The current standard of care for localised tumours is primary surgical resection with neck dissection, which, in the case of locally advanced tumours, may be combined with radiotherapy or chemoradiotherapy.
The novel techniques of spatial labelling (annotation) and navigation-assisted tumour resection being evaluated in this study are intended to enhance the precision of surgical treatment for these tumours, resulting in more R0 resections. In addition, postoperative radiotherapy is expected to be further tailored using the navigation data collected.
The overall aim of the NAVIGATORR study is to improve the local control of head and neck cancer through more precise surgical resection combined with individualised adjuvant radiotherapy.
Cancer patients can participate in the NAVIGATORR study at the NCT in Heidelberg, Berlin, and Tübingen.
The NAVIGATORR study is a prospective, multicentre, feasibility study.
A total of 60 patients with carcinoma of the midface will be enrolled in the single-arm trial.
As part of the study, participants will ondergo navigation-guided tumour resection.
Comprehensive imaging examinations are planned before, during, and after resection of the tumour. These are essential for accurately mapping the tumour and enabling navigation-assisted surgery. During surgery, so-called "tumour resection maps" (TRM) are generated and enriched with histological data. This information is used to individually optimise the subsequent radiotherapy. This approach requires close cooperation between all involved specialist disciplines.
The following assessments are planned at various time points before surgery, prior to radiotherapy, and during follow-up (see Figure 1):
- Multiparametric MRI
- Measurement of circulating tumour DNA
- Collecting and analysing samples of healthy mucous membranes with high radiation exposure (methylome profiling, single-cell proteomics, and total transcriptome analysis if necessary)
The overall aim of the NAVIGATORR trial is to improve the local control of head and neck malignancies by increasing the precision of surgical resection in combination with individualised adjuvant radiotherapy.
- The primary endpoint of the study is to achieve a tumour-free resection margin ("clear margin", tumour distance from the resection margin >5 mm).
- The secondary endpoint of the study is to minimize the radiation dose by using navigation data to plan an individualized dose distribution, thereby reducing expected side effects.
- Additional outcomes include assessment of local tumour control, quality of life, and overall survival of study participants.
Inclusion criteria
- Squamous cell carcinoma (SCC), adenocarcinoma (AC), mucoepidermoid carcinoma (MEC), or adenoid cystic carcinoma (ACC) of the midface, maxilla, or skull base
- Indication for surgical tumour resection confirmed by a multidisciplinary tumour board
- Postoperative radiotherapy is probably indicated.
- Age ≥ 18 years
- The patient's general condition is ≥60% according to the Karnofsky Performance Score
- Signed informed consent
- For women of childbearing age: use of appropriate contraception
- Ability to understand the nature and individual implications of the study
Exclusion criteria
- Contraindications to surgical resection or radiotherapy
- Pregnancy or breastfeeding
- Participation in another clinical trial
1. Presentation of the patient in the tumour conference
Before a patient can be enrolled in the NAVIGATORR trial, the case must be discussed in a multidisciplinary tumour board at one of the participating centres.
At this meeting, it must be confirmed that the tumour is operable and that adjuvant radiotherapy is, in principle, feasible.
2. Contact and initial presentation at the study centre
If this is confirmed, the patient registers at the NCT Heidelberg, Berlin or Tübingen, submitting all (relevant prior) previous findings, or the attending physician does this.
During a personal consultation (baseline visit), the patient is examined and informed about the study by the study physician. Once eligibility is confirmed and written informed consent is obtained, initial assessments — such as multiparametric MRI and blood tests (ctDNA) — are conducted as part of the study, alongside routine imaging (CT)
3. Planning and execution of surgery
The tumour resection is meticulously planned using preoperative imaging data and performed with the aid of an optical navigation system (navigation-guided tumour resection). During the operation, tumour resection maps (TRMs) are generated. In addition, samples are taken from the resection margins (baseline mucosa sampling), and their histopathological data are spatially assigned to the TRMs. Tissue samples are also collected from healthy mucosa.
In most patients, the resulting tissue defects are reconstructed by microsurgery.
4. Postoperative presentation at the study centre
Following the tumour resection, patients return to the study centre for a clinical examination, further imaging (CT and multiparametric MRI), and blood tests (ctDNA) as part of a scheduled study visit.
Adjuvant radiotherapy is then carefully and individually planned based on the data collected before, during, and after surgery.
5. Postoperative adjuvant radiotherapy
During radiotherapy at the NCT Heidelberg, Berlin, or Tübingen, patients undergo clinical assessments and blood sampling (ctDNA) every two weeks as part of their scheduled study visits.
6. Follow-up at the study centre
Study participants are first seen for follow-up 6–8 weeks after completing radiotherapy, and subsequently every three months at the NCT Heidelberg, Berlin, or Tübingen. Each follow-up includes a clinical examination, imaging (multiparametric MRI and CT), blood tests (ctDNA), and quality-of-life assessments.
In addition, tissue samples from the irradiated mucosal areas are taken at the first follow-up and again at 6 and 24 months using a minimally invasive procedure. The follow-up period concludes 24 months after completion of radiotherapy.
Radiooncology Study Centre
Clinic for Radiooncology and Radiotherapy
Heidelberg University Hospital
In the Neuenheimer Feld 400
69120 Heidelberg
Phone: +49 6221-56-38613/-37748/-36318/-32682
Fax: +49 6221-56-1979
E-mail: studien.radonk-at-med.uni-heidelberg.de
Coordinating Principal Investigator
Dr. med. Sebastian Regnery
Klinik für Radioonkologie und Strahlentherapie
Heidelberg University Hospital