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

Primary Purpose

Head and Neck Cancer

Status
Recruiting
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Real-time ADC-guided response adaptive Boost in HNC
Sponsored by
University Hospital Tuebingen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring Radiotherapy, MR-guided Radiotherapy, dose-finding study, MR-Linac, ADC-guided response adaptive Boost

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UKT RadiooncologyRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Adaptive SBRT Boost

Arm Description

Dose-escalated SBRT boost to an ADC-based high risk subvolume in HNC

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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.
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.

Full Information

First Posted
June 1, 2021
Last Updated
January 31, 2022
Sponsor
University Hospital Tuebingen
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1. Study Identification

Unique Protocol Identification Number
NCT05160714
Brief Title
Individualized Response-adaptive Radiation Dose Prescription in HNC Based on MRI
Acronym
MRL-02
Official Title
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"
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2022 (Actual)
Primary Completion Date
March 30, 2023 (Anticipated)
Study Completion Date
March 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Tuebingen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer
Keywords
Radiotherapy, MR-guided Radiotherapy, dose-finding study, MR-Linac, ADC-guided response adaptive Boost

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Dose-finding phase 1 trial with four dose levels and 3+3 design: 12 patients if no DLT occurs up to 24 patients if 1 DLT per dose-level occurs.
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Adaptive SBRT Boost
Arm Type
Experimental
Arm Description
Dose-escalated SBRT boost to an ADC-based high risk subvolume in HNC
Intervention Type
Radiation
Intervention Name(s)
Real-time ADC-guided response adaptive Boost in HNC
Intervention Description
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
Primary Outcome Measure Information:
Title
Dose limiting toxicity (DLT)
Description
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)
Time Frame
At 3 months after radiotherapy
Secondary Outcome Measure Information:
Title
Regional tumor control
Description
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.
Time Frame
After 6 weeks, 3 months and every 3 months up to two years
Title
Disease free survival
Description
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.
Time Frame
During treatment and after 6 weeks, 3 months and every 3 months up to two years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Simon Böke, MD
Phone
49 (0) 7071 29
Ext
82165
Email
ro-info@med.uni-tuebingen.de
First Name & Middle Initial & Last Name or Official Title & Degree
Daniel Zips, MD, Prof.
Phone
49 (0) 7071 29
Ext
82165
Email
ro-info@med.uni-tuebingen.de
Facility Information:
Facility Name
UKT Radiooncology
City
Tübingen
State/Province
BW
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Simon Böke, MD
Phone
+49 7071 29
Ext
82165
Email
roinfo@med.uni-tuebingen.de

12. IPD Sharing Statement

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Individualized Response-adaptive Radiation Dose Prescription in HNC Based on MRI

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