De-Intensification Radiotherapy Postoperative Head Neck

NCT02528955 | Completed Phase 2

• 1 other identifier: DIREKHT
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

In patients with squamous cell carcinoma of the oral cavity, the oropharynx and larynx with \>= pT3 and or pN+ postoperative radio - or radiochemotherapy is the standard of care. Postoperative radiochemotherapy is indicated in patients with multiple lymph node metastasis, lymph node metastasis with extracapsular spread and or R1/2 resection. Locoregional control rates are over 80% after surgery and radio(chemo)therapy. But many patients suffer from therapy-related long-term side-effects, like xerostomia, dysphagia, fibrosis, trismus etc. The aim of this study is to investigate if depending on primary tumor stage, quality of resection ( resection margin) and number of lymph node metastasis and performed neck dissection an adapted de-intensified dose- and target volume concept may be performed without reducing locoregional-control but with reducing radiotherapy-related side-effects.

Conditions

Cancer of Head and Neck

Keywords

Head and neck cancer; postoperative; radiotherapy; de-intensification

Outcome Measures

Primary Outcomes (1)

• locoregional recurrence rate after 2 years

  (recurrence in-radiation field, radiation field margin, outside radiation field for example contralateral)

  after 2 years

Secondary Outcomes (6)

• Overall Survival

  after 2 and 5 years

• disease-free survival

  after 2 and 5 years

• distant-metastasis-free survival

  after 2 and 5 years

• acute toxicity according to ctc-ae v.4.0

  during therapy and up to 8 weeks after therapy

• late toxicity according to ctc-ae v.4.0

  follow-up period (5years)

Study Arms (3)

A:De-Intensification Radiotherapy (RT) primary tumor region

ACTIVE COMPARATOR

A:De-Intensification Radiotherapy (RT) primary tumor region * ≤ pT2, R ≥ 5 mm, L0, Pn0 * \> 3 lymph node metastasis or patients with \< 3 ipsilateral lymph node metastasis and a bilateral primary tumor without adequate contralateral neck dissection

Radiation: A: De-Intensification RT primary tumor region

B:De-Intensification Radiotherapy contralateral lymph nodes

ACTIVE COMPARATOR

* \> pT2 and/or R \< 5mm and/or L1 and/or Pn1 * ≤ 3 ipsilateral lymph node metastasis (and contralateral pN0 (\>= 6 resected lymph nodes) or contralateral cN0 in patients wih strictly ipsilateral localised ( \>= 5 mm distance from midline) cancer of the oral cavity or oropharynx

Radiation: B: De-Intensification RT contralateral lymph nodes

C:De-Intensification RT primary tumor region /contralateral LN

ACTIVE COMPARATOR

* ≤ pT2, R ≥ 5 mm, L0, Pn0 * ≤ 3 ipsilateral lymph node metastasis (and contralateral pN0 (\>= 6 resected lymph nodes) or contralateral cN0 in patients wih strictly ipsilateral localised ( \>= 5 mm distance from midline) cancer of the oral cavity or oropharynx

Radiation: C. De-Intensification RT primary tumor region AND contralateral lymph nodes

Interventions

A: De-Intensification RT primary tumor region RADIATION

A: * Reduction of radiation dose in the primary tumor region to 56 Gy, * Elective Radiotherapy of both neck sides

A:De-Intensification Radiotherapy (RT) primary tumor region

B: De-Intensification RT contralateral lymph nodes RADIATION

B: * No dose reduction in primary tumor region (prescribed dose in primary tumor region: 64 Gy) * Reduction of target volume: only elective radiotherapy of the ipsilateral neck, no contralateral neck irradiation

B:De-Intensification Radiotherapy contralateral lymph nodes

C. De-Intensification RT primary tumor region AND contralateral lymph nodes RADIATION

C: * Reduction of radiation dose in the primary tumor region to 56 Gy, AND * Reduction of target volume: only elective radiotherapy of the ipsilateral neck, no contralateral neck irradiation

C:De-Intensification RT primary tumor region /contralateral LN

Eligibility Criteria

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

You may qualify if:

• Histologic proven squamous cell carcinoma of the oral cavity/larynx/oro- or hypopharynx
• Postoperative tumor status:
• Oral cavity, oropharynx or larynx: pT1-3, pN0-pN2b
• Hypopharynx: pT1-2; pN1
• Patients that fulfill one or both of the following criteria:
• ≤ pT2, R ≥ 5 mm, L0, Pn0
• ≤ 3 ipsilateral lymph node metastases (if a contralateral adequate neck dissection is performed, no contralateral neck dissection is recommended in patients with strictly ipsilateral localised tumors of the oropharynx or oral cavity)
• R0-Resection (resection margin ≥ 1mm)
• No distant metastasis cM0
• age ≥ 18 years, no upper age limit
• ECOG ≤ 2
• Patients that understood protocol contents and are able to behave according to protocol
• Signed study-specific consent form prior to therapy
• In case of indicated simultaneous chemotherapy:
• adequate bone marrow function (leucocytes \> 3,5x10\^3, platelets \> 100x 10\^3, hemoglobin \> 10g/dl

You may not qualify if:

• pregnant or lactating/nursing women
• fertile patients that are not willing to use highly effective methods of contraception (per institutional standards) during treatment
• Any condition potentially hampering compliance with the study protocol and follow-up schedule
• On-treatment participation on other trials
• R1 or R2 resection status
• pN2c and pN3
• cM1
• prior radiotherapy in the head and neck region , prior chemo- or immunotherapy (neoadjuvant/induction)
• time between surgery and beginning of radio(chemo)therapy \> 6 weeks
• Prior (\> 4 months before beginning of radio(chemo)therapy) neck dissection
• In case of indicated simultaneous chemotherapy:
• reduced hearing ability (especially upper frequency range)
• known dihydropyrimidindehydrogenase (DPD) deficiency
• simultaneous therapy with brivudin or other DPD-inhibitors
• uncontrolled serious disease, including physical and mental diseases, for example within last 6 months:instable angina pectoris, heart attack, serious cardiac dysrhythmias, stroke, serious carotid stenosis, neurologic or psychiatric disorders including epilepsy, dementia, psychosis; uncontrolled infection; liver cirrhosis Child B or C, severe hepatic impairment; severe blood count changes; severe renal impairment, HIV

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (1)

Dept. of Radiooncology, University Hospital

Erlangen, 91054, Germany

Location

Related Publications (2)

• Haderlein M, Speer S, Ott O, Lettmaier S, Hecht M, Semrau S, Frey B, Scherl C, Iro H, Kesting M, Fietkau R. Dose Reduction to the Swallowing Apparatus and the Salivary Glands by De-Intensification of Postoperative Radiotherapy in Patients with Head and Neck Cancer: First (Treatment Planning) Results of the Prospective Multicenter DIREKHT Trial. Cancers (Basel). 2020 Feb 26;12(3):538. doi: 10.3390/cancers12030538.

  PMID: 32110958 DERIVED

• Onbasi Y, Lettmaier S, Hecht M, Semrau S, Iro H, Kesting M, Fietkau R, Haderlein M. Is there a patient population with squamous cell carcinoma of the head and neck region who might benefit from de-intensification of postoperative radiotherapy? : A monocentric retrospective analysis of a previously defined low-risk patient population treated with standard-of-care radiotherapy. Strahlenther Onkol. 2019 Jun;195(6):482-495. doi: 10.1007/s00066-018-1415-y. Epub 2019 Jan 4.

  PMID: 30610355 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Study Officials

• Rainer Fietkau

  Dept. of Radiooncology, University Hospital Erlangen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2015
• First Posted: August 19, 2015
• Study Start: October 1, 2014
• Primary Completion: October 1, 2022
• Study Completion: September 1, 2025
• Last Updated: March 17, 2026

Record last verified: 2025-09

Locations

DE (1)