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

Primary Purpose

Head-and-neck Squamous Cell Carcinoma

Status
Recruiting
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
De-escalation radio(chemo)therapy - Level 1
De-escalation radio(chemo)therapy - Level 2
Standard radio(chemotherapy)
Sponsored by
Technische Universität Dresden
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head-and-neck Squamous Cell Carcinoma focused on measuring Head and neck cancer, Oropharyngeal cancer, postoperative, radiotherapy, radiochemotherapy, de-intensification, HPV

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

  • 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

Sites / Locations

  • Prof. Anca-Ligia GrosuRecruiting
  • Prof. Daniel ZipsRecruiting
  • Prof. Claus BelkaRecruiting
  • Prof. Stephanie CombsRecruiting
  • Prof. Claus RödelRecruiting
  • Prof. Martin StuschkeRecruiting
  • Prof. Mechthild KrauseRecruiting
  • Prof. Volker Budach
  • Prof. Jürgen DebusRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Active Comparator

Active Comparator

Arm Label

Interventional Arm A - HPV(+)

Interventional Arm B - HPV(+)

Observational Arm A - HPV(-)

Observational Arm B - HPV(+)

Arm Description

De-escalation Radio(chemo)therapy - Level 1

De-escalation Radio(chemo)therapy - Level 2

Standard Radio(chemo)therapy

Standard Radio(chemo)therapy

Outcomes

Primary Outcome Measures

rate of locoregional recurrences
measured from the last day of treatment

Secondary Outcome Measures

overall survival
measured from the last day 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.
late toxicity
The occurrence of late side effects will be recorded and documented based on CTCAE 4.0 after every follow-up visit.
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.
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.
rate of locoregional recurrences
measured from the last day of treatment

Full Information

First Posted
October 24, 2017
Last Updated
September 8, 2023
Sponsor
Technische Universität Dresden
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
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1. Study Identification

Unique Protocol Identification Number
NCT03396718
Brief Title
De-escalation of Adjuvant Radio (Chemo) Therapy for HPV-positive Head-neck Squamous Cell Carcinomas
Acronym
DELPHI
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 4, 2018 (Actual)
Primary Completion Date
November 30, 2029 (Anticipated)
Study Completion Date
November 30, 2032 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Technische Universität Dresden
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

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head-and-neck Squamous Cell Carcinoma
Keywords
Head and neck cancer, Oropharyngeal cancer, postoperative, radiotherapy, radiochemotherapy, de-intensification, HPV

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
304 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Interventional Arm A - HPV(+)
Arm Type
Experimental
Arm Description
De-escalation Radio(chemo)therapy - Level 1
Arm Title
Interventional Arm B - HPV(+)
Arm Type
Experimental
Arm Description
De-escalation Radio(chemo)therapy - Level 2
Arm Title
Observational Arm A - HPV(-)
Arm Type
Active Comparator
Arm Description
Standard Radio(chemo)therapy
Arm Title
Observational Arm B - HPV(+)
Arm Type
Active Comparator
Arm Description
Standard Radio(chemo)therapy
Intervention Type
Radiation
Intervention Name(s)
De-escalation radio(chemo)therapy - Level 1
Intervention Description
54/ 59,4 Gy
Intervention Type
Radiation
Intervention Name(s)
De-escalation radio(chemo)therapy - Level 2
Intervention Description
48,8/ 55 Gy
Intervention Type
Radiation
Intervention Name(s)
Standard radio(chemotherapy)
Intervention Description
60/ 66 Gy
Primary Outcome Measure Information:
Title
rate of locoregional recurrences
Description
measured from the last day of treatment
Time Frame
24 months after end of treatment
Secondary Outcome Measure Information:
Title
overall survival
Description
measured from the last day of treatment
Time Frame
60 months and 5 years after end of treatment
Title
acute toxicity
Description
The occurrence of acute side effects (up to 90 days after start of treatment) will be recorded and documented based on CTCAE 4.0.
Time Frame
3 months after end of treatment
Title
late toxicity
Description
The occurrence of late side effects will be recorded and documented based on CTCAE 4.0 after every follow-up visit.
Time Frame
24 months after end of treatment
Title
quality of life of cancer patients
Description
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.
Time Frame
24 months after end of treatment
Title
quality of life - disease specific
Description
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.
Time Frame
24 months after end of treatment
Title
rate of locoregional recurrences
Description
measured from the last day of treatment
Time Frame
5 years after end of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 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: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mechthild Krause, Prof.
Phone
+49 351 458 2238
Email
mechthild.krause@uniklinikum-dresden.de
First Name & Middle Initial & Last Name or Official Title & Degree
Fabian Lohaus, MD
Phone
+49 351 458 2238
Email
fabian.lohaus@uniklinikum-dresden.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mechthild Krause, Prof.
Organizational Affiliation
University of Technology, University Hospital Carl Gustav Carus, Department of Radiation Therapy and Radiation Oncology, German Consortium for Translational Cancer Research (DKTK)
Official's Role
Study Chair
Facility Information:
Facility Name
Prof. Anca-Ligia Grosu
City
Freiburg
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
79106
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anca-Ligia Grosu, Prof.
Phone
+49 761 270 94610
Email
anca.grosu@uniklinik-freiburg.de
First Name & Middle Initial & Last Name & Degree
Ana-Ligia Grosu, Prof.
Facility Name
Prof. Daniel Zips
City
Tübingen
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
72016
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Zips, Prof.
Phone
+49 7071/29-8 21 65
Email
ROInfo@med.uni-tuebingen.de
First Name & Middle Initial & Last Name & Degree
Daniel Zips, Prof.
Facility Name
Prof. Claus Belka
City
München
State/Province
Bavaria
ZIP/Postal Code
81377
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claus Belka, Prof.
Phone
+49 89 7095 4520
Email
Claus.Belka@med.uni-muenchen.de
First Name & Middle Initial & Last Name & Degree
Claus Belka, Prof.
Facility Name
Prof. Stephanie Combs
City
München
State/Province
Bavaria
ZIP/Postal Code
81675
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephanie Combs, Prof.
Phone
+49 89 41 40-45 02
Email
radonk@lrz.tum.de
First Name & Middle Initial & Last Name & Degree
Stephanie Combs, Prof.
Facility Name
Prof. Claus Rödel
City
Frankfurt am Main
State/Province
Hesse
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claus Rödel, Prof.
Facility Name
Prof. Martin Stuschke
City
Essen
State/Province
North Rhine-Westphalia
ZIP/Postal Code
45147
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Stuschke, Prof.
Phone
+49 201 / 723-23 20
Email
martin.stuschke@uk-essen.de
First Name & Middle Initial & Last Name & Degree
Martin Stuschke, Prof.
Facility Name
Prof. Mechthild Krause
City
Dresden
State/Province
Saxony
ZIP/Postal Code
01307
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mechthild Krause, Prof.
Phone
+493514582238
Email
str.studien@uniklinikum-dresden.de
Facility Name
Prof. Volker Budach
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Volker Budach, Prof.
Phone
+49 30 450 527 152
First Name & Middle Initial & Last Name & Degree
Volker Budach, Prof.
Facility Name
Prof. Jürgen Debus
City
Heidelberg
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jürgen Debus, Prof.

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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