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Trial record 1 of 1 for:    DIREKHT
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De-Intensification Radiotherapy Postoperative Head Neck (DIREKHT)

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ClinicalTrials.gov Identifier: NCT02528955
Recruitment Status : Recruiting
First Posted : August 19, 2015
Last Update Posted : August 19, 2015
Sponsor:
Information provided by (Responsible Party):
University of Erlangen-Nürnberg Medical School

Tracking Information
First Submitted Date  ICMJE August 10, 2015
First Posted Date  ICMJE August 19, 2015
Last Update Posted Date August 19, 2015
Study Start Date  ICMJE October 2014
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2015)
locoregional recurrence rate after 2 years [ Time Frame: after 2 years ]
(recurrence in-radiation field, radiation field margin, outside radiation field for example contralateral)
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2015)
  • Overall Survival [ Time Frame: after 2 and 5 years ]
  • disease-free survival [ Time Frame: after 2 and 5 years ]
  • distant-metastasis-free survival [ Time Frame: after 2 and 5 years ]
  • acute toxicity according to ctc-ae v.4.0 [ Time Frame: during therapy and up to 8 weeks after therapy ]
  • late toxicity according to ctc-ae v.4.0 [ Time Frame: follow-up period (5years) ]
  • Quality of Life as measured by questionaires [ Time Frame: before and during treatment and in the follow-up for 5 years ]
    questionaires: EORTC QLQ-C30 and QLQ-H&N35 and EAT-10
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE De-Intensification Radiotherapy Postoperative Head Neck
Official Title  ICMJE De-intensification of Postoperative Radiotherapy in Selected Patients With Head and Neck Cancer
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.

Detailed 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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cancer of Head and Neck
Intervention  ICMJE
  • 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
  • Radiation: 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
  • Radiation: 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
Study Arms  ICMJE
  • Active Comparator: A:De-Intensification Radiotherapy (RT) primary tumor region

    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
    Intervention: Radiation: A: De-Intensification RT primary tumor region
  • Active Comparator: B:De-Intensification Radiotherapy contralateral lymph nodes
    • > 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: Radiation: B: De-Intensification RT contralateral lymph nodes
  • Active Comparator: C:De-Intensification RT primary tumor region /contralateral LN
    • ≤ 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: Radiation: C. De-Intensification RT primary tumor region AND contralateral lymph nodes
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 18, 2015)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2021
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Marlen Haderlein 004991318533996 marlen.haderlein@uk-erlangen.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02528955
Other Study ID Numbers  ICMJE DIREKHT
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Erlangen-Nürnberg Medical School
Study Sponsor  ICMJE University of Erlangen-Nürnberg Medical School
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Rainer Fietkau Dept. of Radiooncology, University Hospital Erlangen
PRS Account University of Erlangen-Nürnberg Medical School
Verification Date August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP