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De-escalation of Adjuvant Radio (Chemo) Therapy for HPV-positive Head-neck Squamous Cell Carcinomas (DELPHI)

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ClinicalTrials.gov Identifier: NCT03396718
Recruitment Status : Recruiting
First Posted : January 11, 2018
Last Update Posted : February 18, 2019
Sponsor:
Collaborators:
German Cancer Research Center
National Center for Tumor Diseases (NCT) Dresden
National Center for Tumor Diseases, Heidelberg
Radiation Oncology Working Group of the German Cancer Society
Information provided by (Responsible Party):
Mechthild Krause, Technische Universität Dresden

Brief Summary:

In patients with squamous cell carcinoma of the oral cavity, the oropharynx and larynx with local advanced tumors (pathologic stage T3 = pT3) and or lymph node involvement (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 residual tumor (R1-Status) after resection. Oropharyngeal cancer caused by HPV (human papillomavirus 16 or 18) is a distinct subgroup with a known sensitivity to radiotherapy (RTx) or radiochemotherapy (RCTx). Additionally a superior outcome after R(C)Tx over HPV negative patients was shown for patients treated with primary or adjuvant RCTx. To date it is unknown if the total dose of the radiotherapy can be safely reduced with the aim to decrease the therapy associated late effects.

Patients with a HPV associated carcinoma that take part in the study will be treated with a reduced radiotherapy dose, chemotherapy will be prescribed based on clinical factors (number of affected lymph node, presence of extracapsular spread or residual tumor). Radiation dose will be reduced in two steps.


Condition or disease Intervention/treatment Phase
Head-and-neck Squamous Cell Carcinoma Radiation: De-escalation radio(chemo)therapy - Level 1 Radiation: De-escalation radio(chemo)therapy - Level 2 Radiation: Standard radio(chemotherapy) Not Applicable

Detailed Description:
For all patients taking part in the study the HPV status of the resected tumor will be determined centrally by p16 immunohistochemistry and confirmation will be done by HPV DNA assessment using Polymerase Chain Reaction (PCR)-based array. Patients positive for HPV will be treated with a reduced RT dose to the tumor and to elective neck. HPV negative patients will be treated with standard radio- or radiochemotherapy. Patients deemed at high risk for locoregional recurrences (presence of extracapsular spread, residual tumor or multiple affected nodes) will be treated separately from patients deemed at intermediate risk (T>=3, and / or 1-3 nodes positive). The high risk group will be treated with a higher dose and concurrent chemotherapy. After inclusion of 30 patients per treatment group, follow up for the patients will be awaited for two years and safety of the intervention will be assessed. The second de-escalation level will only be opened for accrual if not more than three locoregional recurrences will occur per treatment group.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 384 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: De-escalation of Adjuvant Radio (Chemo) Therapy for HPV-positive Head and Neck Squamous Cell Carcinomas: A Phase I Study to Reduce Late Toxicity
Actual Study Start Date : September 4, 2018
Estimated Primary Completion Date : January 2026
Estimated Study Completion Date : January 2029

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Interventional Arm A - HPV(+)
De-escalation Radio(chemo)therapy - Level 1
Radiation: De-escalation radio(chemo)therapy - Level 1
54/ 59,4 Gy

Experimental: Interventional Arm B - HPV(+)
De-escalation Radio(chemo)therapy - Level 2
Radiation: De-escalation radio(chemo)therapy - Level 2
48,8/ 55 Gy

Active Comparator: Observational Arm A - HPV(-)
Standard Radio(chemo)therapy
Radiation: Standard radio(chemotherapy)
60/ 66 Gy

Active Comparator: Observational Arm B - HPV(+)
Standard Radio(chemo)therapy
Radiation: Standard radio(chemotherapy)
60/ 66 Gy




Primary Outcome Measures :
  1. rate of locoregional recurrences [ Time Frame: 24 months after end of treatment ]
    measured from the last day of treatment


Secondary Outcome Measures :
  1. overall survival [ Time Frame: 60 months and 5 years after end of treatment ]
    measured from the last day of treatment

  2. acute toxicity [ Time Frame: 3 months after end of treatment ]
    The occurrence of acute side effects (up to 90 days after start of treatment) will be recorded and documented based on CTCAE 4.0.

  3. late toxicity [ Time Frame: 24 months after end of treatment ]
    The occurrence of late side effects will be recorded and documented based on CTCAE 4.0 after every follow-up visit.

  4. quality of life of cancer patients [ Time Frame: 24 months after end of treatment ]
    The assessment of quality of life (QoL) is carried out using the EORTC quality of life questionnaire (QLQ) C30. Quality of life will be documented immediately before the start of therapy, after completion of postoperative radiotherapy and at every follow-up visit. QOL will be measured as change from baseline over time.

  5. quality of life - disease specific [ Time Frame: 24 months after end of treatment ]
    The assessment of quality of life (QOL) is carried out using the EORTC quality of life questionnaire (QLQ) disease-specific module for head and neck cancer H&N35. Quality of life will be documented immediately before the start of therapy, after completion of postoperative radiotherapy and at every follow-up visit. QOL will be measured as change from baseline over time.

  6. rate of locoregional recurrences [ Time Frame: 5 years after end of treatment ]
    measured from the last day of treatment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Condition after surgical removal of a squamous cell carcinoma of the oropharynx and adequate lymph node dissection
  • Indication for adjuvant radiotherapy or radiochemotherapy in the interdisciplinary tumor board
  • Good general state (ECOG performance status 0 or 1)
  • Adequate compliance to ensure closely follow-up
  • Patient's consent and written consent
  • Neck dissection of at least the tumor bearing side

Additional Inclusion Criteria Arm intermediate risk (at least one of the criteria must be fulfilled):

  • pT3 and R0 and / or
  • histologically confirmed involvement of lymph nodes (n = 1-3) and no extracapsular extension of the lymph node metastasis

Additional Inclusion Criteria Arm high risk (at least one of the criteria must be fulfilled):

  • residual tumor (R1 status) and / or
  • pathologic stage T4 (pT4) status and / or
  • more than 3 infected lymph nodes and / or
  • extracapsular extension of at least one lymph node metastasis

Exclusion Criteria:

  • cumulative nicotine abuse > 30 packyears
  • radiologically presumed or histologically confirmed distant metastasis
  • R2 resection or macroscopically visible residual tumor after surgery
  • no neck dissection
  • interval between last operation and planned irradiation start > 7 weeks
  • contraindication against a guideline-appropriate adjuvant radiation or radiochemotherapy according to the clinical risk constellation
  • tumor disease in the last five years before the beginning of the study (except basaliomas of the skin, in-situ carcinoma of the cervix uteri or breast, or tumors with similar prognosis which are considered to be very likely to be cured)
  • malignant tumor disease in the head and neck region, regardless of interval and prognosis
  • Pre-irradiation with risk of dose overlap
  • participation in another clinical trial if further experimental therapy is necessary or the treatments/ protocols are mutually exclusive (e.g. altered chemotherapy, additional consolidation chemotherapy). Allowed is the additional participation in observation studies or supportive therapy studies.
  • diseases or conditions which do not allow the person concerned to assess the nature and scope and possible consequences of the clinical trial
  • pregnant or lactating women
  • evidence that the participant is not expected to comply with the study protocol (e.g. lack of cooperation)
  • missing written consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03396718


Contacts
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Contact: Mechthild Krause, Prof. +49 351 458 2238 mechthild.krause@uniklinikum-dresden.de
Contact: Fabian Lohaus, MD +49 351 458 2238 fabian.lohaus@uniklinikum-dresden.de

Locations
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Germany
Prof. Anca-Ligia Grosu Not yet recruiting
Freiburg, Baden-Wuerttemberg, Germany, 79106
Contact: Anca-Ligia Grosu, Prof.    +49 761 270 94610    anca.grosu@uniklinik-freiburg.de   
Principal Investigator: Ana-Ligia Grosu, Prof.         
Prof. Daniel Zips Not yet recruiting
Tübingen, Baden-Wuerttemberg, Germany, 72016
Contact: Daniel Zips, Prof.    +49 7071/29-8 21 65    ROInfo@med.uni-tuebingen.de   
Principal Investigator: Daniel Zips, Prof.         
Prof. Claus Belka Not yet recruiting
München, Bavaria, Germany, 81377
Contact: Claus Belka, Prof.    +49 89 7095 4520    Claus.Belka@med.uni-muenchen.de   
Principal Investigator: Claus Belka, Prof.         
Prof. Stephanie Combs Not yet recruiting
München, Bavaria, Germany, 81675
Contact: Stephanie Combs, Prof.    +49 89 41 40-45 02    radonk@lrz.tum.de   
Principal Investigator: Stephanie Combs, Prof.         
Prof. Claus Rödel Not yet recruiting
Frankfurt am Main, Hesse, Germany
Contact: Claus Rödel, Prof.         
Prof. Martin Stuschke Not yet recruiting
Essen, North Rhine-Westphalia, Germany, 45147
Contact: Martin Stuschke, Prof.    +49 201 / 723-23 20    martin.stuschke@uk-essen.de   
Principal Investigator: Martin Stuschke, Prof.         
Prof. Mechthild Krause Recruiting
Dresden, Saxony, Germany, 01307
Contact: Mechthild Krause, Prof.    +493514582238    str.studien@uniklinikum-dresden.de   
Prof. Volker Budach Not yet recruiting
Berlin, Germany, 10117
Contact: Volker Budach, Prof.    +49 30 450 527 152      
Principal Investigator: Volker Budach, Prof.         
Prof. Jürgen Debus Not yet recruiting
Heidelberg, Germany
Contact: Jürgen Debus, Prof.         
Prof. Heinz Schmidberger Not yet recruiting
Mainz, Germany
Contact: Heinz Schmidberger, Prof.         
Sponsors and Collaborators
Technische Universität Dresden
German Cancer Research Center
National Center for Tumor Diseases (NCT) Dresden
National Center for Tumor Diseases, Heidelberg
Radiation Oncology Working Group of the German Cancer Society
Investigators
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Study Chair: Mechthild Krause, Prof. University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Therapy and Radiation Oncology, German Consortium for Translational Cancer Research (DKTK)
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Responsible Party: Mechthild Krause, Director of the Department of Radiotherapy and Radiation Oncology, Technische Universität Dresden
ClinicalTrials.gov Identifier: NCT03396718    
Other Study ID Numbers: STR-DELPHI-2016
First Posted: January 11, 2018    Key Record Dates
Last Update Posted: February 18, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Mechthild Krause, Technische Universität Dresden:
Head and neck cancer
Oropharyngeal cancer
postoperative
radiotherapy
radiochemotherapy
de-intensification
HPV
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site