Individualized Response-adaptive Radiation Dose Prescription in HNC Based on MRI (MRL-02)

Individualized Response-adaptive Radiation Dose Prescription in HNC Based on MRI - Real-time ADC-guided Response Adaptive Boost in HNC - "Individuelle MR-basierte Dosisverschreibung Bei Kopf-Hals-Tumoren - ADC-basierter Adaptiver Boost"

This Phase 1 dose-finding study investigates the maximal tolerated dose for a subsequent phase 2 trial testing MR-guided individualized response-adaptive dose prescription in HNC.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Radiation: Real-time ADC-guided response adaptive Boost in HNC

Detailed Description

This single-center, non-randomized interventional dose-finding phase I trial evaluates the maximal tolerated boost dose with respect to dose limiting toxicities in patients with locally advanced head and neck squamous cell carcinoma (UICC stage III/IVB) with an indication for a primary radiochemotherapy. The primary aim of the trial is to define the maximal tolerated dose in an ADC-based subvolume using an adaptive SBRT-boost areal. Dose-escalated SBRT boost to ADC-high risk volume will be delivered once a week and is defined according to the the actual imaging immediately performed prior to delivery (real-time adaptive) i.e. it can vary from one week to another and it might also be reduced throughout the course of treatment (response adaptive). In case of complete disappearance of high-risk subvolumes sufficient large enough to boost (<5ml), no further ADC boost but only the floor-boost dose is given. The dose escalation of the ADC-high risk volume boost is graduated in four dose levels of 5x5 Gy, 5x5.5 Gy, 5x6 Gy, 5x6.5 Gy in a classical 3+3 dose-finding design where 3 patients per radiation dose level are enrolled. Primary endpoint is the dose limiting toxicity, any acute and late non-hematologic grade 4 or 5 related to the radiotherapy intervention, ≥ grade 3 CTC v.5. oral mucositis at 3 months after radiotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Simon Böke, MD; Phone Number: 82165 49 (0) 7071 29; Email: ro-info@med.uni-tuebingen.de
• Study Contact Backup: Name: Daniel Zips, MD, Prof.; Phone Number: 82165 49 (0) 7071 29; Email: ro-info@med.uni-tuebingen.de

Study Locations

• Germany
  • BW
    • Tübingen, BW, Germany, 72076
      • Recruiting
      • UKT Radiooncology
      • Contact: Simon Böke, MD; Phone Number: 82165 +49 7071 29; Email: roinfo@med.uni-tuebingen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: older than 18 years
• WHO (ECOG) performance status 0-2
• Histological proven HNC (squamous cell carcinoma)
• HPV negative tumors or high risk HPV positive tumors
• Stage III - IVB HNC of the hypopharynx, oropharynx and oral cavity according to UICC and AJCC guidelines
• Tumor extension and localization suitable for radiochemotherapy with curative intent
• Simultaneous standard chemotherapy with cisplatin applicable (no contra-indications)
• Dental examination and -treatment before start of therapy
• For women with childbearing potential and men in reproductive ages adequate contraception.
• Ability of subject to understand character and individual consequences of the clinical trial
• Written informed consent (must be available before enrolment in the trial)

Exclusion Criteria:

• Refusal of the patients to take part in the trial
• Presence of distant metastases (UICC stage IVC)
• HPV positive tumors UICC Stage III with T1/2 N3, despite of smoking status
• Previous radiotherapy in the head and neck region
• Second malignancy that is likely to require treatment during the trial intervention or follow-up period or that, in the opinion of the physician, has a considerable risk of recurrence or metastases within the follow-up period
• Serious disease or medical condition with life expectancy of less than one year
• Participation in competing interventional trial on cancer treatment
• Patients who are not suitable for radiochemotherapy
• Pregnant or lactating women
• Patients not able to understand the character and individual consequences of the trial
• Nasopharyngeal and glottis laryngeal carcinomas
• Patients with contraindications for magnet-resonance tomography

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adaptive SBRT Boost; Dose-escalated SBRT boost to an ADC-based high risk subvolume in HNC	Radiation: Real-time ADC-guided response adaptive Boost in HNC; 40 Gy in 20 fractions over 5 weeks (Monday to Thursday) to the adjuvant neck, simultaneous integrated boost with 56 Gy in 20 fractions in 5 weeks to the low-risk macroscopic tumor. Once weekly Dose-escalated SBRT adaptive boost to an ADC-based high risk subvolume with graduated dose levels of 5x5 Gy, 5x5.5 Gy, 5x6 Gy, 5x6.5 Gy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity (DLT)	Dose limiting toxicity (DLT): any acute and late grade 4 or 5 related to the intervention, ≥ grade 3 CTC v.5. oral mucositis at 3 months after radiotherapy (persistent mucosal ulceration or inflammation in the high dose region with severe pain; interfering with oral intake; limiting self-care ADL)	At 3 months after radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regional tumor control	Regional tumor control will be measured by clinical H&N examinations at six weeks and then every three months up to two years. Imaging follow-up includes MRI at 6 weeks and 3 months, FDG-PET CT at 3 months and further CTs every 3 month.	After 6 weeks, 3 months and every 3 months up to two years
Disease free survival	Clinical H&N examinations at six weeks and then every three months up to two years, including MRI at 6 weeks and 3 months, FDG-PET CT at 3 months and further CTs every 3 month.	During treatment and after 6 weeks, 3 months and every 3 months up to two years

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Anticipated): March 30, 2023
• Study Completion (Anticipated): March 30, 2025

Study Registration Dates

• First Submitted: June 1, 2021
• First Submitted That Met QC Criteria: December 2, 2021
• First Posted (Actual): December 16, 2021

Study Record Updates

• Last Update Posted (Actual): February 1, 2022
• Last Update Submitted That Met QC Criteria: January 31, 2022
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Radiotherapy; MR-Linac; dose-finding study; MR-guided Radiotherapy; ADC-guided response adaptive Boost
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms
• Other Study ID Numbers: 081/2021B01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No