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

NCT ID: NCT03396718

Last Updated: 2025-09-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 304 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-29
• Study Completion Date: 2032-11-30

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) 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.

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 first 10 patients of the of the first de-escalation level 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 less than 2 locoregional recurrences will occur within the first 10 patients per treatment group.

Conditions

Head-and-neck Squamous Cell Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Interventional Arm A - HPV(+)

De-escalation Radio(chemo)therapy - Level 1

Group Type: EXPERIMENTAL

De-escalation radio(chemo)therapy - Level 1

Intervention Type: RADIATION

55/ 59,4 Gy (intermediate / high risk group)

Interventional Arm B - HPV(+)

De-escalation Radio(chemo)therapy - Level 2

Group Type: EXPERIMENTAL

De-escalation radio(chemo)therapy - Level 2

Intervention Type: RADIATION

48,4/ 55 Gy (intermediate / high risk group)

Observational Arm A - HPV(-)

Standard Radio(chemo)therapy

Group Type: ACTIVE_COMPARATOR

Standard radio(chemotherapy)

Intervention Type: RADIATION

60/ 66 Gy (intermediate / high risk group)

Observational Arm B - HPV(+)

Standard Radio(chemo)therapy

Group Type: ACTIVE_COMPARATOR

Standard radio(chemotherapy)

Intervention Type: RADIATION

60/ 66 Gy (intermediate / high risk group)

Interventions

De-escalation radio(chemo)therapy - Level 1

55/ 59,4 Gy (intermediate / high risk group)

Intervention Type: RADIATION

De-escalation radio(chemo)therapy - Level 2

48,4/ 55 Gy (intermediate / high risk group)

Intervention Type: RADIATION

Standard radio(chemotherapy)

60/ 66 Gy (intermediate / high risk group)

Intervention Type: RADIATION

Eligibility 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

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

• 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

• Patients with a cumulative nicotine abuse > 30 packyears. These patients are not included in the intervention arms, but are always included in the observation arms (regardless of HPV status).
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German Cancer Research Center

OTHER

Sponsor Role: collaborator

National Center for Tumor Diseases (NCT) Dresden

UNKNOWN

Sponsor Role: collaborator

National Center for Tumor Diseases, Heidelberg

OTHER

Sponsor Role: collaborator

Radiation Oncology Working Group of the German Cancer Society

OTHER

Sponsor Role: collaborator

Technische Universität Dresden

OTHER

Sponsor Role: lead

Responsible Party

Mechthild Krause

Director of the Department of Radiotherapy and Radiation Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mechthild Krause, Prof.

Role: STUDY_CHAIR

University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Therapy and Radiation Oncology, German Consortium for Translational Cancer Research (DKTK)

Locations

University Clinic Tübingen

Tübingen, Baden-Wurttemberg, Germany

Site Status: RECRUITING

University Clinic Essen

Essen, North Rhine-Westphalia, Germany

Site Status: RECRUITING

University Clinic Dresden

Dresden, Saxony, Germany

Site Status: RECRUITING

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Site Status: NOT_YET_RECRUITING

University Clinic Frankfurt

Frankfurt am Main, , Germany

Site Status: RECRUITING

University Clinic Freiburg

Freiburg im Breisgau, , Germany

Site Status: RECRUITING

University Clinic Heidelberg

Heidelberg, , Germany

Site Status: RECRUITING

LMU Munich University Hospital

München, , Germany

Site Status: RECRUITING

TUM University Hospital

München, , Germany

Site Status: RECRUITING

University Clinic Regensburg

Regensburg, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Mechthild Krause, Prof.

Role: CONTACT

mechthild.krause@uniklinikum-dresden.de

+49 351 458 2238

Fabian Lohaus, MD

Role: CONTACT

fabian.lohaus@uniklinikum-dresden.de

+49 351 458 2238

Facility Contacts

Maximilian Niyazi, Prof.

Role: primary

ROInfo@med.uni-tuebingen.de

07071 29-82165

Martin Stuschke, Prof. Dr.

Role: primary

Role: backup

Maja.guberina@uk-essen.de

Mechthild Krause, Prof.

Role: primary

str.studien@uniklinikum-dresden.de

+493514582238

Daniel Zips, Prof.

Role: primary

Role: backup

marcus.beck@charite.de

Claus Rödel, Prof. Dr.

Role: primary

Role: backup

Fleischmann@med.uni-frankfurt.de

Anca-Ligia Grosu, Prof. Dr.

Role: primary

anca.grosu@uniklinik-freiburg.de

Jürgen Debus, Prof. Dr.

Role: primary

Role: backup

Thomas.Held@med.uni-heidelberg.de

Claus Belka, Prof. Dr.

Role: primary

Claus.Belka@med.uni-muenchen.de

Stephanie Combs, Prof. Dr.

Role: primary

radonk@lrz.tum.de

Oliver Kölbl, Prof. Dr.

Role: primary

oliver.koelbl@ukr.de

Role: backup

f.steger@ukr.de

Other Identifiers

STR-DELPHI-2016

Identifier Type: -

Identifier Source: org_study_id