Head-and-neck Squamous Cell CarcinomaDELPHINCT03396718
De-escalation of Adjuvant Radio (Chemo) Therapy for HPV-positive Head-neck Squamous Cell Carcinomas
A study testing De-escalation radio(chemo)therapy - Level 1, De-escalation radio(chemo)therapy - Level 2 and Standard radio(chemotherapy) in people with Head-and-neck Squamous Cell Carcinoma, run by Technische Universität Dresden at 10 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head-and-neck Squamous Cell Carcinoma
- What is being tested?
- De-escalation radio(chemo)therapy - Level 1, De-escalation radio(chemo)therapy - Level 2 and Standard radio(chemotherapy)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 304 participants
- Where
- 10 sitesGermany
- Study dates
- 29 Nov 2018to 30 Nov 2032
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 14Show fewer
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
Germany10 sites, 10 recruiting
- Not yet recruiting
Charité - Universitätsmedizin Berlin
Berlin, 13353
Daniel Zips, Prof.
marcus.beck@charite.de
- Recruiting
University Clinic Dresden
Dresden, Saxony, 01307
Mechthild Krause, Prof., +493514582238, str.studien@uniklinikum-dresden.de
- Recruiting
University Clinic Essen
Essen, North Rhine-Westphalia, 45147
Martin Stuschke, Prof. Dr.
Maja.guberina@uk-essen.de
- Recruiting
University Clinic Frankfurt
Frankfurt am Main, 60590
Claus Rödel, Prof. Dr.
Fleischmann@med.uni-frankfurt.de
- Recruiting
University Clinic Freiburg
Freiburg im Breisgau, 79106
Anca-Ligia Grosu, Prof. Dr., anca.grosu@uniklinik-freiburg.de
Ana-Ligia Grosu, Prof. Dr.
- Recruiting
University Clinic Heidelberg
Heidelberg, 69120
Jürgen Debus, Prof. Dr.
Thomas.Held@med.uni-heidelberg.de
- Recruiting
LMU Munich University Hospital
München, 81377
Claus Belka, Prof. Dr., Claus.Belka@med.uni-muenchen.de
Claus Belka, Prof. Dr.
- Recruiting
TUM University Hospital
München, 81675
Stephanie Combs, Prof. Dr., radonk@lrz.tum.de
Stephanie Combs, Prof. Dr.
- Recruiting
University Clinic Regensburg
Regensburg, 93053
Oliver Kölbl, Prof. Dr., oliver.koelbl@ukr.de
f.steger@ukr.de
- Recruiting
University Clinic Tübingen
Tübingen, Baden-Wurttemberg, 72016
Maximilian Niyazi, Prof., 07071 29-82165, ROInfo@med.uni-tuebingen.de
Simon Böke, Dr
About this study
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
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.
Read the 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
- Being tested
- De-escalation radio(chemo)therapy - Level 1, De-escalation radio(chemo)therapy - Level 2, Standard radio(chemotherapy)
- Keywords
- Head and neck cancer, Oropharyngeal cancer, postoperative, radiotherapy, radiochemotherapy, de-intensification, HPV
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Head and Neck Neoplasms, Oropharyngeal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
De-escalation radio(chemo)therapy - Level 1Radiation
55/ 59,4 Gy (intermediate / high risk group)
De-escalation radio(chemo)therapy - Level 2Radiation
48,4/ 55 Gy (intermediate / high risk group)
Standard radio(chemotherapy)Radiation
60/ 66 Gy (intermediate / high risk group)
| Study group | Role | What they receive |
|---|---|---|
| Interventional Arm A - HPV(+) | Experimental | De-escalation Radio(chemo)therapy - Level 1 Receives: Radiation: De-escalation radio(chemo)therapy - Level 1 |
| Interventional Arm B - HPV(+) | Experimental | De-escalation Radio(chemo)therapy - Level 2 Receives: Radiation: De-escalation radio(chemo)therapy - Level 2 |
| Observational Arm A - HPV(-) | Active comparator | Standard Radio(chemo)therapy Receives: Radiation: Standard radio(chemotherapy) |
| Observational Arm B - HPV(+) | Active comparator | Standard Radio(chemo)therapy Receives: Radiation: Standard radio(chemotherapy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
rate of locoregional recurrences
measured from the last day of treatment
Measured: 24 months after end of treatment
Secondary outcomes (6)
overall survival
measured from the last day of treatment
Measured: 60 months and 5 years after end of treatment
acute toxicity
The occurrence of acute side effects (up to 90 days after start of treatment) will be recorded and documented based on CTCAE 4.0.
Measured: 3 months after end of treatment
late toxicity
The occurrence of late side effects will be recorded and documented based on CTCAE 4.0 after every follow-up visit.
Measured: 24 months after end of treatment
quality of life of cancer patients
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.
Measured: 24 months after end of treatment
quality of life - disease specific
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.
Measured: 24 months after end of treatment
rate of locoregional recurrences
measured from the last day of treatment
Measured: 5 years after end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2018
- Study start29 Nov 2018
- Primary completion30 Nov 2029 (estimated)
- Study completion30 Nov 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Head-and-neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Technische Universität DresdenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 304 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Technische Universität Dresden
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Principal investigator, Mechthild Krause, Technische Universität Dresden
- Investigators
- Mechthild Krause, Prof., Study chair, University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Therapy and Radiation Oncology, German Consortium for Translational Cancer Research (DKTK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03396718
- Sponsor's protocol ID
- STR-DELPHI-2016
- Acronym
- DELPHI
- Status last verified
- Sep 2025
- First submitted
- 24 Oct 2017
- Last updated
- 22 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Linge A, Lohaus F, Appold S, Troost EGC, Abdollahi A, Kowal S, Buttner D, Lock S, Baumann M, Krause M. De-escalation of adjuvant radio(chemo)therapy for patients with HPV-positive head and neck squamous cell carcinoma: study protocol for a phase I trial to reduce late toxicity (DELPHI). BMC Cancer. 2026 Apr 29;26(1):542. doi: 10.1186/s12885-026-16050-x.
PubMed 42057029
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03396718
- Acronym / sponsor ID
- DELPHI / STR-DELPHI-2016
- Conditions
- Head-and-neck Squamous Cell Carcinoma
- Keywords
- Head and neck cancer, Oropharyngeal cancer, postoperative, radiotherapy, radiochemotherapy, de-intensification, HPV
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 304 participants (estimated)
- Lead sponsor
- Technische Universität DresdenUniversity, hospital or other
- 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
- Study start
- 29 Nov 2018 (actual)
- Primary completion
- 30 Nov 2029 (estimated)
- Study completion
- 30 Nov 2032 (estimated)
- First posted
- 11 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Interventional Arm A - HPV(+) | Experimental | Radiation: De-escalation radio(chemo)therapy - Level 1De-escalation Radio(chemo)therapy - Level 1 |
| Interventional Arm B - HPV(+) | Experimental | Radiation: De-escalation radio(chemo)therapy - Level 2De-escalation Radio(chemo)therapy - Level 2 |
| Observational Arm A - HPV(-) | Active comparator | Radiation: Standard radio(chemotherapy)Standard Radio(chemo)therapy |
| Observational Arm B - HPV(+) | Active comparator | Radiation: Standard radio(chemotherapy)Standard Radio(chemo)therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| De-escalation radio(chemo)therapy - Level 155/ 59,4 Gy (intermediate / high risk group) | Radiation | Interventional Arm A - HPV(+) |
| De-escalation radio(chemo)therapy - Level 248,4/ 55 Gy (intermediate / high risk group) | Radiation | Interventional Arm B - HPV(+) |
| Standard radio(chemotherapy)60/ 66 Gy (intermediate / high risk group) | Radiation | Observational Arm A - HPV(-), Observational Arm B - HPV(+) |
Primary outcome
rate of locoregional recurrences
Time frame: 24 months after end of treatment
measured from the last day of treatment
6 secondary outcomes
overall survival
Time frame: 60 months and 5 years after end of treatment
acute toxicity
Time frame: 3 months after end of treatment
late toxicity
Time frame: 24 months after end of treatment
quality of life of cancer patients
Time frame: 24 months after end of treatment
quality of life - disease specific
Time frame: 24 months after end of treatment
rate of locoregional recurrences
Time frame: 5 years after end of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2025.
- Derived from this study: PubMed 42057029Linge A, Lohaus F, Appold S, Troost EGC, Abdollahi A, Kowal S, Buttner D, Lock S, Baumann M, Krause M. De-escalation of adjuvant radio(chemo)therapy for patients with HPV-positive head and neck squamous cell carcinoma: study protocol for a phase I trial to reduce late toxicity (DELPHI). BMC Cancer. 2026 Apr 29;26(1):542. doi: 10.1186/s12885-026-16050-x.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mechthild Krause, Prof. study chair
University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Therapy and Radiation Oncology, German Consortium for Translational Cancer Research (DKTK)
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing De-escalation radio(chemo)therapy - Level 1, De-escalation radio(chemo)therapy - Level 2 and Standard radio(chemotherapy) in people with Head-and-neck Squamous Cell Carcinoma, run by Technische Universität Dresden at 10 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mechthild Krause, Prof. (+49 351 458 2238, mechthild.krause@uniklinikum-dresden.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
rate of locoregional recurrences (time frame: 24 months after end of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03396718, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2025.