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

Head-and-neck Squamous Cell Carcinoma Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03396718
• Other study ID #: STR-DELPHI-2016
• Status: Recruiting
• Phase: N/A
• Start date: September 4, 2018
• Est. completion date: November 30, 2032

Study information

• Verified date: September 2023
• Source: Technische Universität Dresden
• Contact: Mechthild Krause, Prof.
• Phone: +49 351 458 2238
• Email: mechthild.krause[@]uniklinikum-dresden.de
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 304
• Est. completion date: November 30, 2032
• Est. primary completion date: November 30, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head-and-neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Radiation:
• De-escalation radio(chemo)therapy - Level 1
54/ 59,4 Gy
• De-escalation radio(chemo)therapy - Level 2
48,8/ 55 Gy
• Standard radio(chemotherapy)
60/ 66 Gy

Locations

Country	Name	City	State
Germany	Prof. Volker Budach	Berlin
Germany	Prof. Mechthild Krause	Dresden	Saxony
Germany	Prof. Martin Stuschke	Essen	North Rhine-Westphalia
Germany	Prof. Claus Rödel	Frankfurt am Main	Hesse
Germany	Prof. Anca-Ligia Grosu	Freiburg	Baden-Wuerttemberg
Germany	Prof. Jürgen Debus	Heidelberg
Germany	Prof. Claus Belka	München	Bavaria
Germany	Prof. Stephanie Combs	München	Bavaria
Germany	Prof. Daniel Zips	Tübingen	Baden-Wuerttemberg

Sponsors (5)

Lead Sponsor	Collaborator
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

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	rate of locoregional recurrences	measured from the last day of treatment	24 months after end of treatment
Secondary	overall survival	measured from the last day of treatment	60 months and 5 years after end of treatment
Secondary	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.	3 months after end of treatment
Secondary	late toxicity	The occurrence of late side effects will be recorded and documented based on CTCAE 4.0 after every follow-up visit.	24 months after end of treatment
Secondary	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.	24 months after end of treatment
Secondary	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.	24 months after end of treatment
Secondary	rate of locoregional recurrences	measured from the last day of treatment	5 years after end of treatment