Thermotherapy for Head and Neck Cancer Patients

NCT07690618 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: NL-011902
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Hypopharyngeal Carcinoma; Oropharyngeal Carcinoma; Laryngeal Carcinoma; Head and Neck Squamous Cell Carcinoma; Oral Cavity Carcinoma; Head and Neck Cancer; Locally Advanced Head and Neck Carcinoma

Keywords

Hyperthermia; Thermotherapy; Phase 1 trial; Chemoradiotherapy; Radiosensitization; Safety; Tolerability; Locoregional Control; Locally advanced cancer

Outcome Measures

Primary Outcomes (3)

• 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.

  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

  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.

  7 weeks (treatment period)

Study Arms (2)

Thermotherapy adjuvant to chemoradiotherapy

EXPERIMENTAL

This primary cohort will consist of patients recieving thermotherapy adjuvant to standard chemoradiotherapy for LAHNC. Dose-escalation is performed in this cohort.

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 LAHNC. Prospective registration of safety and tolerability is performed in this cohort.

Other: Thermotherapy; Radiation: Radiotherapy

Interventions

Thermotherapy OTHER

Patients will receive thermotherapy once weekly, adjuvant to standard of care (chemo)radiotherapy.

Also known as: Hyperthermia

Thermotherapy adjuvant to chemoradiotherapy; Thermotherpy adjuvant to radiotherapy monotherapy

Radiotherapy RADIATION

Standard of care radiotherapy, often 70 Gy in 35 daily fractions, 5 times per week.

Thermotherpy adjuvant to radiotherapy monotherapy

Concurrent chemoradiation RADIATION

Standard of care chemoradiotherapy, 70 Gy in 35 daily fractions, 5 times per week with concurrent platinum based chemotherapy (cisplatin or carboplatin).

Thermotherapy adjuvant to chemoradiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Curative intent treatment with radiotherapy monotherapy in primary setting

You may not qualify if:

• Patients previously treated by radiation on the same target volume.
• Any condition or circumstance potentially hampering compliance with the follow-up schedule.

Sponsors & Collaborators

• Sensius BV: collaborator
• Erasmus Medical Center: lead
• Dutch Cancer Society: collaborator

Study Sites (1)

Erasmus Medical Center

Rotterdam, South Holland, 3015 CD, Netherlands

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Oropharyngeal Neoplasms; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Mouth Neoplasms; Hyperthermia

Interventions

Hyperthermia, Induced; Diathermy; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Mouth Diseases; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heat Stress Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Michiel Kroesen, MD, Dr.

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michiel Kroesen, MD, Dr.

CONTACT

+31107041116; m.kroesen@erasmusmc.nl

Tessa L. Coenraad, MSc

CONTACT

+31107041116; t.coenraad@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Radiation Oncologist

Model Details: The trial includes two single-arm interventional cohorts. In both groups, patients will recieve the same intervention, being thermotherapy.

Study Record Dates

• First Submitted: July 1, 2026
• First Posted: July 8, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): November 1, 2031
• Last Updated: July 8, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)