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

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorTechnische Universität Dresden

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Sequential

Treatments tested in this trial

  • De-escalation radio(chemo)therapy - Level 1

    Radiation

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

  • De-escalation radio(chemo)therapy - Level 2

    Radiation

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

  • Standard radio(chemotherapy)

    Radiation

    60/ 66 Gy (intermediate / high risk group)

Treatment groups

304 Participants
are divided into 4 treatment groups
Group A: Interventional Arm A - HPV(+)Experimental treatment 1 intervention
Group B: Interventional Arm B - HPV(+)Experimental treatment 1 intervention
Group C: Observational Arm A - HPV(-)Active comparator 1 intervention
Group D: Observational Arm B - HPV(+)Active comparator 1 intervention

Trial outcomes

Primary outcomes

1

rate of locoregional recurrences

measured from the last day of treatment

Time frame
24 months after end of treatment

Secondary outcomes

1

overall survival

measured from the last day of treatment

Time frame
60 months and 5 years after end of treatment
2

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.

Time frame
3 months after end of treatment
3

late toxicity

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
4

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.

Time frame
24 months after end of treatment

Other outcomes

Sponsors and contacts

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Technische Universität Dresden

Lead sponsor

German Cancer Research Center

Collaborator

National Center for Tumor Diseases (NCT) Dresden

Collaborator

National Center for Tumor Diseases, Heidelberg

Collaborator

Radiation Oncology Working Group of the German Cancer Society

Collaborator