Head and Neck CancerPhase 1TANCAP-INCT07690618
Thermotherapy for Head and Neck Cancer Patients
A Phase 1 study testing Thermotherapy, Radiotherapy and Concurrent chemoradiation in people with Head and Neck Cancer and Oropharyngeal Carcinoma, run by Erasmus Medical Center at 1 site in Netherlands.
Trial summary
This phase I, single-center study evaluates the safety, tolerability, and recommended phase II dose (RP2D) of mild hyperthermia (thermotherapy) when added to standard-of-care treatment in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Oropharyngeal Carcinoma, Hypopharyngeal Carcinoma
- What is being tested?
- Thermotherapy, Radiotherapy and Concurrent chemoradiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Sep 2026to Nov 2031
- Phase
- Phase 1
- 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
None listed.
Who cannot join
- Patients previously treated by radiation on the same target volume.
- Any condition or circumstance potentially hampering compliance with the follow-up schedule.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Erasmus Medical Center
Rotterdam, South Holland, 3015 CD
Michiel Kroesen, MD, Dr., +31107041116, m.kroesen@erasmusmc.nl
About this study
Official title: Thermotherapy for Locally Advanced Head and Neck Cancer Patients in Primary Setting - a Phase I Dose-finding Study
This phase I, single-center study evaluates the safety, tolerability, and recommended phase II dose (RP2D) of mild hyperthermia (thermotherapy) when added to standard-of-care treatment in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC). Tumor recurrence remains common despite chemoradiotherapy, highlighting the need for treatment intensification. Thermotherapy, which increases tumor temperature to 39-45°C, may enhance the effect of the treatment.
The study consists of two components: (1) a dose-escalation cohort in patients receiving definitive chemoradiotherapy, using a Time-to-Event Bayesian Optimal Interval (TiTE-BOIN) design to determine the RP2D based on dose-limiting toxicities (DLTs) and treatment tolerability; and (2) a parallel cohort of patients receiving radiotherapy alone, in whom thermotherapy is administered at dose levels previously shown to be safe and tolerable in the chemoradiotherapy cohort to evaluate tolerability in this patient population.
Read more
Besides the safety and tolerability of the thermotherapy RP2D, the secondary objectives include evaluation of safety in patients receiving radiotherapy alone, as well as exploratory assessment of tumor control and survival outcomes.
This study aims to support the development of safe and feasible thermotherapy-based treatment strategies to improve locoregional control and outcomes in patients with LAHNSCC.
Read the detailed description
Locoregionally advanced head and neck cancer (LAHNC) carries a substantial risk of locoregional recurrence despite curative-intent chemoradiotherapy. Most recurrences arise within high-dose radiation regions, suggesting that additional intensification of locoregional therapy may be required. Thermotherapy (mild hyperthermia) is a non-invasive, local regional treatment that can enhance the effect of radiotherapy and chemotherapy by multiple working mechanisms, including improving tissue oxygenation, inhibiting DNA-repair mechanisms, and stimulating immune response. Before thermotherapy can be integrated into curative-intent treatment for LAHNC, its safety and tolerability in combination with (chemo)radiotherapy must be established in a prospective setting.
Previous work at Erasmus MC with the first-generation HyperCollar and the next-generation HyperCollar3D involved patients with recurrent or second-primary HNSCC receiving re-irradiation with thermotherapy. These cohorts suggested a possible dose-dependent relationship between the delivered energy and acute trismus, with fewer events observed after dose reduction. Although these findings were encouraging, the re-irradiation population is not directly representative of patients with primary LAHNC. Consequently, the optimal and safely deliverable thermotherapy dose for primary disease remains unknown, and prospective dose-finding in a chemoradiotherapy setting is needed.
The TANCAP-I trial is a prospective phase I study evaluating the safety, tolerability, and highest safely deliverable thermotherapy dose in LAHNC. The study consists of two single-arm cohorts. The primary cohort includes patients receiving definitive chemoradiotherapy and serves as the dose-escalation cohort. Dose escalation is guided by the Time-to-Event Bayesian Optimal Interval (TITE-BOIN) design, which incorporates the timing of toxicity events and allows for efficient, ethically balanced dose escalation, using mild trismus (mouth opening limited <35 mm) as the guiding DLT. The secondary cohort consists of patients receiving radiotherapy monotherapy for whom chemotherapy is contraindicated. In this group, thermotherapy safety and tolerability will be prospectively recorded without independent dose escalation.
For both groups, thermotherapy will be administered once weekly using the HyperCollar3D device, which enables precise, patient-specific deep heating of the primary tumor and involved lymph nodes. The applied thermotherapy dose is defined by Specific Absorption Rate (W/kg) in 50cc healthy tissues. Optional invasive temperature measurements may be performed in a subset of participants under separate consent.
Safety and tolerability will be assessed at baseline, throughout treatment and up to 6 months following completion. Dose-limiting toxicities (DLTs) include mild trismus and predefined severe grade III-IV toxicities. Tolerability is defined by a participant's ability to complete planned thermotherapy sessions.
Results from the TANCAP-I trial will inform the recommended phase 2 dose (RP2D) and provide the foundation for future studies evaluating whether adjuvant thermotherapy can safely enhance locoregional control and improve outcomes for patients with LAHNC.
- Conditions
- Head and Neck Cancer, Oropharyngeal Carcinoma, Hypopharyngeal Carcinoma, Laryngeal Carcinoma, Head and Neck Squamous Cell Carcinoma, Oral Cavity Carcinoma
- Being tested
- Thermotherapy, Radiotherapy, Concurrent chemoradiation
- Keywords
- Hyperthermia, Thermotherapy, Phase 1 trial, Chemoradiotherapy, Radiosensitization, Safety, Tolerability, Locoregional Control, Locally advanced cancer
- Medical subject headings
- Head and Neck Neoplasms, Oropharyngeal Neoplasms, Hypopharyngeal Neoplasms, Laryngeal Neoplasms, Squamous Cell Carcinoma of Head and Neck, Mouth Neoplasms, Hyperthermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThermotherapyOther
Also called Hyperthermia
Patients will receive thermotherapy once weekly, adjuvant to standard of care (chemo)radiotherapy.
RadiotherapyRadiation
Standard of care radiotherapy, often 70 Gy in 35 daily fractions, 5 times per week.
Concurrent chemoradiationRadiation
Standard of care chemoradiotherapy, 70 Gy in 35 daily fractions, 5 times per week with concurrent platinum based chemotherapy (cisplatin or carboplatin).
| Study group | Role | What they receive |
|---|---|---|
| Thermotherapy adjuvant to chemoradiotherapy | Experimental | This primary cohort will consist of patients recieving thermotherapy adjuvant to standard chemoradiotherapy for locally advanced head and neck cancer. Dose-escalation is performed in this cohort. Receives: Other: Thermotherapy; Radiation: Concurrent chemoradiation |
| Thermotherpy adjuvant to radiotherapy monotherapy | Experimental | This parallel cohort will consist of patients recieving thermotherapy adjuvant to standard radiotherapy monotherapy for locally advanced head and neck cancer. Prospective registration of safety and tolerability is performed in this cohort. Receives: Other: Thermotherapy; Radiation: Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity: mild trismus
Trismus is objectively scored by measuring the mouth opening using a caliper according to standardized protocol. When the mouth opening is <35 mm, the patient is scored with trismus and this will be a dose limiting toxicity (DLT). Using a Time to Event Bayesian Optimal Interval Design, we will determine dose (de)escalation with an incidence threshold of 55% in the primary cohort.
Measured: 8 months (treatment period + follow-up)
Dose Limiting Toxicities
Upon occurence of the following DLTs, the dose level will be stopped immediately for further inclusion: • Grade III trismus • Grade IV mucositis • Grade IV dermatitis • Grade III or IV osteo- or soft tissue necrosis • Grade IV Burn wound • Grade IV tumor hemorrhage • Grade IV laryngeal edema
Measured: 8 months (treatment period + follow-up)
Tolerability of thermotherapy dose
Tolerability of the thermotherapy dose is defined as the ability of ≥66% of the patients to successfully complete ≥40% of the planned thermotherapy fractions. If the dose level does not meet these criteria, the dose level is considered intolerable and is eliminated.
Measured: 7 weeks (treatment period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2026
- Study start1 Sep 2026 (estimated)
- Primary completion31 Aug 2028 (estimated)
- Study completionNov 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The trial includes two single-arm interventional cohorts. In both groups, patients will recieve the same intervention, being thermotherapy.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Dutch Cancer Society, Sensius BV
- Responsible party
- Principal investigator, Michiel Kroesen, Erasmus Medical Center
- Investigators
- Michiel Kroesen, MD, Dr., Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07690618
- Sponsor's protocol ID
- NL-011902
- Acronym
- TANCAP-I
- Status last verified
- Aug 2026
- First submitted
- 1 Jul 2026
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thermotherapy for Locally Advanced Head and Neck Cancer Patients in Primary Setting - a Phase I Dose-finding Study
- ClinicalTrials.gov ID
- NCT07690618
- Acronym / sponsor ID
- TANCAP-I / NL-011902
- Conditions
- Head and Neck Cancer, Oropharyngeal Carcinoma, Hypopharyngeal Carcinoma, Laryngeal Carcinoma, Head and Neck Squamous Cell Carcinoma, Oral Cavity Carcinoma
- Keywords
- Hyperthermia, Thermotherapy, Phase 1 trial, Chemoradiotherapy, Radiosensitization, Safety, Tolerability, Locoregional Control
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- Dutch Cancer Society, Sensius BV
- Study start
- 1 Sep 2026 (estimated)
- Primary completion
- 31 Aug 2028 (estimated)
- Study completion
- Nov 2031 (estimated)
- First posted
- 8 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I, single-center study evaluates the safety, tolerability, and recommended phase II dose (RP2D) of mild hyperthermia (thermotherapy) when added to standard-of-care treatment in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC). Tumor recurrence remains common despite chemoradiotherapy, highlighting the need for treatment intensification. Thermotherapy, which increases tumor temperature to 39-45°C, may enhance the effect of the treatment.
The study consists of two components: (1) a dose-escalation cohort in patients receiving definitive chemoradiotherapy, using a Time-to-Event Bayesian Optimal Interval (TiTE-BOIN) design to determine the RP2D based on dose-limiting toxicities (DLTs) and treatment tolerability; and (2) a parallel cohort of patients receiving radiotherapy alone, in whom thermotherapy is administered at dose levels previously shown to be safe and tolerable in the chemoradiotherapy cohort to evaluate tolerability in this patient population.
Besides the safety and tolerability of the thermotherapy RP2D, the secondary objectives include evaluation of safety in patients receiving radiotherapy alone, as well as exploratory assessment of tumor control and survival outcomes.
This study aims to support the development of safe and feasible thermotherapy-based treatment strategies to improve locoregional control and outcomes in patients with LAHNSCC.
Detailed description
Locoregionally advanced head and neck cancer (LAHNC) carries a substantial risk of locoregional recurrence despite curative-intent chemoradiotherapy. Most recurrences arise within high-dose radiation regions, suggesting that additional intensification of locoregional therapy may be required. Thermotherapy (mild hyperthermia) is a non-invasive, local regional treatment that can enhance the effect of radiotherapy and chemotherapy by multiple working mechanisms, including improving tissue oxygenation, inhibiting DNA-repair mechanisms, and stimulating immune response. Before thermotherapy can be integrated into curative-intent treatment for LAHNC, its safety and tolerability in combination with (chemo)radiotherapy must be established in a prospective setting.
Previous work at Erasmus MC with the first-generation HyperCollar and the next-generation HyperCollar3D involved patients with recurrent or second-primary HNSCC receiving re-irradiation with thermotherapy. These cohorts suggested a possible dose-dependent relationship between the delivered energy and acute trismus, with fewer events observed after dose reduction. Although these findings were encouraging, the re-irradiation population is not directly representative of patients with primary LAHNC. Consequently, the optimal and safely deliverable thermotherapy dose for primary disease remains unknown, and prospective dose-finding in a chemoradiotherapy setting is needed.
The TANCAP-I trial is a prospective phase I study evaluating the safety, tolerability, and highest safely deliverable thermotherapy dose in LAHNC. The study consists of two single-arm cohorts. The primary cohort includes patients receiving definitive chemoradiotherapy and serves as the dose-escalation cohort. Dose escalation is guided by the Time-to-Event Bayesian Optimal Interval (TITE-BOIN) design, which incorporates the timing of toxicity events and allows for efficient, ethically balanced dose escalation, using mild trismus (mouth opening limited <35 mm) as the guiding DLT. The secondary cohort consists of patients receiving radiotherapy monotherapy for whom chemotherapy is contraindicated. In this group, thermotherapy safety and tolerability will be prospectively recorded without independent dose escalation.
For both groups, thermotherapy will be administered once weekly using the HyperCollar3D device, which enables precise, patient-specific deep heating of the primary tumor and involved lymph nodes. The applied thermotherapy dose is defined by Specific Absorption Rate (W/kg) in 50cc healthy tissues. Optional invasive temperature measurements may be performed in a subset of participants under separate consent.
Safety and tolerability will be assessed at baseline, throughout treatment and up to 6 months following completion. Dose-limiting toxicities (DLTs) include mild trismus and predefined severe grade III-IV toxicities. Tolerability is defined by a participant's ability to complete planned thermotherapy sessions.
Results from the TANCAP-I trial will inform the recommended phase 2 dose (RP2D) and provide the foundation for future studies evaluating whether adjuvant thermotherapy can safely enhance locoregional control and improve outcomes for patients with LAHNC.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The trial includes two single-arm interventional cohorts. In both groups, patients will recieve the same intervention, being thermotherapy.
| Arm | Type | Receives |
|---|---|---|
| Thermotherapy adjuvant to chemoradiotherapy | Experimental | Other: Thermotherapy, Radiation: Concurrent chemoradiationThis primary cohort will consist of patients recieving thermotherapy adjuvant to standard chemoradiotherapy for locally advanced head and neck cancer. Dose-escalation is performed in this cohort. |
| Thermotherpy adjuvant to radiotherapy monotherapy | Experimental | Other: Thermotherapy, Radiation: RadiotherapyThis parallel cohort will consist of patients recieving thermotherapy adjuvant to standard radiotherapy monotherapy for locally advanced head and neck cancer. Prospective registration of safety and tolerability is performed in this cohort. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (2 listed)
- Patients previously treated by radiation on the same target volume.
- Any condition or circumstance potentially hampering compliance with the follow-up schedule.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ThermotherapyAlso: HyperthermiaPatients will receive thermotherapy once weekly, adjuvant to standard of care (chemo)radiotherapy. | Other | Thermotherapy adjuvant to chemoradiotherapy, Thermotherpy adjuvant to radiotherapy monotherapy |
| RadiotherapyStandard of care radiotherapy, often 70 Gy in 35 daily fractions, 5 times per week. | Radiation | Thermotherpy adjuvant to radiotherapy monotherapy |
| Concurrent chemoradiationStandard of care chemoradiotherapy, 70 Gy in 35 daily fractions, 5 times per week with concurrent platinum based chemotherapy (cisplatin or carboplatin). | Radiation | Thermotherapy adjuvant to chemoradiotherapy |
Primary outcome
Dose Limiting Toxicity: mild trismus
Time frame: 8 months (treatment period + follow-up)
Trismus is objectively scored by measuring the mouth opening using a caliper according to standardized protocol. When the mouth opening is <35 mm, the patient is scored with trismus and this will be a dose limiting toxicity (DLT). Using a Time to Event Bayesian Optimal Interval Design, we will determine dose (de)escalation with an incidence threshold of 55% in the primary cohort.
Dose Limiting Toxicities
Time frame: 8 months (treatment period + follow-up)
Upon occurence of the following DLTs, the dose level will be stopped immediately for further inclusion: • Grade III trismus • Grade IV mucositis • Grade IV dermatitis • Grade III or IV osteo- or soft tissue necrosis • Grade IV Burn wound • Grade IV tumor hemorrhage • Grade IV laryngeal edema
Tolerability of thermotherapy dose
Time frame: 7 weeks (treatment period)
Tolerability of the thermotherapy dose is defined as the ability of ≥66% of the patients to successfully complete ≥40% of the planned thermotherapy fractions. If the dose level does not meet these criteria, the dose level is considered intolerable and is eliminated.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michiel Kroesen, MD, Dr. principal investigator
Erasmus Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Thermotherapy, Radiotherapy and Concurrent chemoradiation in people with Head and Neck Cancer and Oropharyngeal Carcinoma, run by Erasmus Medical Center at 1 site in Netherlands.
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 0 inclusion and 2 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 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Michiel Kroesen, MD, Dr. (+31107041116, m.kroesen@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity: mild trismus (time frame: 8 months (treatment period + follow-up)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Sep 2026.