De-Intensification Radiotherapy Postoperative Head Neck

Cancer of Head and Neck Clinical Trial

— DIREKHT  

Official title:

De-intensification of Postoperative Radiotherapy in Selected Patients With Head and Neck Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02528955
• Other study ID #: DIREKHT
• Status: Recruiting
• Phase: Phase 2
• First received: August 10, 2015
• Last updated: August 18, 2015
• Start date: October 2014
• Est. completion date: October 2021

Study information

• Verified date: August 2015
• Source: University of Erlangen-Nürnberg Medical School
• Contact: Marlen Haderlein
• Phone: 004991318533996
• Email: marlen.haderlein[@]uk-erlangen.de
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial 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.

Description:

The study is a non-randomized phase-II trial. In total there are 3 therapy arms.

Patients are assigned to one of these therapy arms according to the tumor status and the quality and kind of surgery. The aim of this study is to investigate if a risk-adapted dose- and target-volume concept in clearly defined patient groups is possible to individualize postoperative radiotherapy without reducing locoregional-control but with reducing radiotherapy-related side-effects.

There are two main issues to investigate:

1. Dose prescription in primary tumor region:

In this study it should be investigated if a dose reduction to 56 Gy in the primary tumor region is possible, if the resection margin is >= 5mm, tumor stage is <=pT2 and if there are no other risk factors like perineural spread or peritumoral lymphangiosis.

2. Target volume definition in elective lymph node levels

It should be investigated if ipsilateral cervical lymph irradiation alone allows adequate locoregional control in selected patients:

ipsilateral lymph node metastasis <=3 and contralateral pN0 (adequate contralateral selective neck dissection performed) or contralateral cN0 (in patients with strictly ipsilateral localized tumors of the oral cavity or oropharynx)

Considering these facts 3 therapy groups are possible:

A:

Criteria:

• 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

Intervention:

• Reduction of radiation dose in the primary tumor region to 56 Gy,

• Elective Radiotherapy of both neck sides

B:

Criteria:

•> 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

Intervention

•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

C:

Criteria

• 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

Intervention

•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

In all arms the dose prescription for the lymph node regions is as follows:

•elective lymph node level (either ipsi- or bilateral): 50 Gy

•lymph node level with lymph node metastasis without extracapsular extension: 56Gy

• lymph node level with lymph node metastasis with extracapsular extension: 64 Gy

In all arms simultaneously chemotherapy is recommended in the following cases:

• lymph node metastasis with extracapsular extension •>= 3 lymph node metastasis

All patients are stratified according to HPV status.

Additional investigations:

• swallowing endoscopy (before, 6 and 24 months after radiotherapy)

• translational research (especially individual radiosensitivity, immunologic parameters in peripheral blood during treatment)

• QoL

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: October 2021
• Est. primary completion date: October 2019
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologic proven squamous cell carcinoma of the oral cavity/larynx/oro- or hypopharynx

2. Postoperative tumor status:

• Oral cavity, oropharynx or larynx: pT1-3, pN0-pN2b

• Hypopharynx: pT1-2; pN1

3. 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)

4. R0-Resection (resection margin = 1mm)

5. No distant metastasis cM0

6. age = 18 years, no upper age limit

7. ECOG = 2

8. Patients that understood protocol contents and are able to behave according to protocol

9. Signed study-specific consent form prior to therapy

10. In case of indicated simultaneous chemotherapy:

• adequate bone marrow function (leucocytes > 3,5x10^3, platelets > 100x 10^3, hemoglobin > 10g/dl

• sufficient liver function: bilirubin < 2,0mg/dl, ALT, AST < less than 3 times upper limit of normal

• sufficient renal function: normal serum creatinine, glomerular filtration rate > 60ml/min

Exclusion Criteria:

1. pregnant or lactating/nursing women

2. fertile patients that are not willing to use highly effective methods of contraception (per institutional standards) during treatment

3. Any condition potentially hampering compliance with the study protocol and follow-up schedule

4. On-treatment participation on other trials

5. R1 or R2 resection status

6. pN2c and pN3

7. cM1

8. prior radiotherapy in the head and neck region , prior chemo- or immunotherapy (neoadjuvant/induction)

9. time between surgery and beginning of radio(chemo)therapy > 6 weeks

10. Prior (> 4 months before beginning of radio(chemo)therapy) neck dissection

11. 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer of Head and Neck
• Head and Neck Neoplasms

Intervention

Radiation:
• A: De-Intensification RT primary tumor region
A: Reduction of radiation dose in the primary tumor region to 56 Gy, Elective Radiotherapy of both neck sides
• B: De-Intensification RT contralateral lymph nodes
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
• C. De-Intensification RT primary tumor region AND contralateral lymph nodes
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

Locations

Country	Name	City	State
Germany	Dept. of Radiooncology, University Hospital	Erlangen

Sponsors (1)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	locoregional recurrence rate after 2 years	(recurrence in-radiation field, radiation field margin, outside radiation field for example contralateral)	after 2 years	Yes
Secondary	Overall Survival		after 2 and 5 years	No
Secondary	disease-free survival		after 2 and 5 years	No
Secondary	distant-metastasis-free survival		after 2 and 5 years	No
Secondary	acute toxicity according to ctc-ae v.4.0		during therapy and up to 8 weeks after therapy	No
Secondary	late toxicity according to ctc-ae v.4.0		follow-up period (5years)	No
Secondary	Quality of Life as measured by questionaires	questionaires: EORTC QLQ-C30 and QLQ-H&N35 and EAT-10	before and during treatment and in the follow-up for 5 years	No