De-Intensification of Postoperative Radiotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck (DIREKHT2)

This randomized, prospective, multicenter phase II/III trial will study the reduction of radiation volume by eliminating radiotherapy (RT) to the elective neck using strictly defined surgical and radio-oncological standards to reduce radiotherapy-related long-term side effects without affecting locoregional control.

Study Overview

• Status: Recruiting
• Conditions: Squamous Cell Carcinoma of the Larynx; Squamous Cell Carcinoma of the Oral Cavity; Squamous Cell Carcinoma of the Oropharynx; Squamous Cell Carcinoma of the Hypopharynx
• Intervention / Treatment: Radiation: RT standard of care; Radiation: Eliminating RT to the elective neck

Detailed Description

This study aims to determine whether it is possible to achieve an individual target volume concept that eliminates elective irradiation of uninvolved lymph drainage areas while maintaining clearly defined surgical standards and using modern imaging and radiation techniques. The aim of this study is to achieve reduced late toxicity without compromising locoregional control.

Patients will be randomized to: either RT to primary tumor region, regions with lymph node metastases and elective nodal irradiation (control arm) or RT to primary tumor region and regions with lymph node metastases without elective nodal irradiation (investigational arm)

A two-stage design was chosen for this purpose.

Phase II:

A randomized phase II study whose primary endpoint is the 1-year percutaneous endoscopic gastrostomy (PEG) tube dependence rate will be performed first.

Phase III:

If the primary endpoint of the phase II study is met and the interim analysis shows no increase in the locoregional recurrence rate in the study/investigational arm, the study will be continued as a phase III study whose primary endpoint is the locoregional control rate.

• Study Type: Interventional
• Enrollment (Estimated): 508
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Marlen Haderlein, PD; Phone Number: 33968 +49913185; Email: marlen.haderlein@uk-erlangen.de
• Study Contact Backup: Name: Studiensekretariat; Phone Number: 33968 +49913185; Email: studiensekretariat.ST@uk-erlangen.de

Study Locations

• Germany
  • Bavaria
    • Erlangen, Bavaria, Germany, 91054
      • Recruiting
      • Universitätsklinikum Erlangen, Strahlenklinik
      • Contact: Marlen Haderlein, PD; Phone Number: 33968 +49913185; Email: marlen.haderlein@uk-erlangen.de
      • Contact: Rainer Fietkau, Prof; Phone Number: 33968 +49913185; Email: rainer.fietkau@uk-erlangen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically proven squamous cell carcinoma of the oral cavity/larynx/oro-or hypopharynx (except glottis cancer (pT1/2pN0))
2. Surgery of primary tumor and neck dissection performed according to predefined surgical standard
3. Indication for postoperative radio(chemo)therapy
4. No lymph node metastases > 6cm
5. Lymph node metastases in not more than 3 lymph node level
6. No distant metastases (cM0)
7. Age ≥ 18 years, no upper age limit
8. Eastern Cooperative Oncology Group (ECOG) ≤ 2
9. Patients who understood protocol contents and are able to behave according to protocol
10. Signed study-specific consent form prior to therapy
11. Start of radiotherapy at least 6 weeks after last tumor-specific surgery (e.g. resection primary tumor, neck dissection, excluded are surgeries according to wound healing complications)

Exclusion Criteria:

1. macroscopic incomplete resection R2
2. Distant metastases (cM1)
3. Radiologically or histologically proven early recurrence after surgery (time frame from surgery to start of radio(chemo)therapy)
4. Lymph node metastases in > 3 lymph node level
5. pregnant or lactating/nursing women
6. fertile patients that are not willing to use highly effective methods of contraception (per institutional standards) during treatment
7. Any condition potentially hampering compliance with the study protocol and follow-up schedule
8. On-treatment participation on other clinical therapeutic trials
9. Prior tumor-specific therapy any other than surgery (like prior radiotherapy in the head and neck region, prior chemo- or immunotherapy (neoadjuvant/induction))
10. Patients who have contraindication for MRI and CT with contrast agent (both)
11. Prior (> 2 months before beginning of radio(chemo)therapy) neck dissection or surgery in the head and neck area affecting lymph drainage
12. History of another primary malignancy except for malignancy treated with curative intent and with no known active disease ≥5 years before diagnosis of head and neck cancer, adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, adequately treated carcinoma in situ without evidence of disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Arm; postoperative radiotherapy of the head and neck region according to current standard including elective nodal irradiation	Radiation: RT standard of care; postoperative radiotherapy of the head and neck region according to current standard including elective nodal irradiation
Experimental: Investigational Arm; postoperative radiotherapy of the head and neck region without elective nodal irradiation	Radiation: Eliminating RT to the elective neck; Reduction of radiation volume by eliminating radiotherapy to the elective neck

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase II: 1-year PEG feeding tube dependence rate	observe change of PEG-dependence due to different target volumes	PEG-dependent 1 year after radiotherapy
Phase III: Time to local relapse	difference between the date of randomization and the date of observation of local relapse (LR), or the date of last observation if no LR occurred (censored observation)	From the date of randomization until the date of observation of local relapse or the date of last observation if no LR occurred, whichever came first (assessed up to 26 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	Disease-free survival	up to 26 months
Distant-metastasis-free survival	Distant-metastasis-free survival	through study completion, an average of 26 months
Overall survival (OS)	Overall survival (OS)	up to 26 months
Cause of death (tumor-related, not tumor-related)	Cause of death (tumor-related, not tumor-related)	through study completion, an average of 26 months
Acute toxicity according to Common Terminology Criteria (CTC) version 5.0	Acute toxicity according to CTC version 5.0	up to 2 months
Late toxicity according to CTC version 5.0	Late toxicity according to CTC version 5.0	up to 24 months

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School
• Investigators: Study Director: Sarina Müller, PD, Universitätsklinikum Erlangen, HNO; Principal Investigator: Rainer Fietkau, Prof, Universitätsklinikum Erlangen, Radiation Oncology

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2024
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): September 1, 2033

Study Registration Dates

• First Submitted: August 11, 2023
• First Submitted That Met QC Criteria: September 8, 2023
• First Posted (Actual): September 11, 2023

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: DIREKHT2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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