Description:
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.
Title
- Brief Title: De-escalation of Adjuvant Radio (Chemo) Therapy for HPV-positive Head-neck Squamous Cell Carcinomas
- 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 IDs
- ORG STUDY ID:
STR-DELPHI-2016
- NCT ID:
NCT03396718
Conditions
- Head-and-neck Squamous Cell Carcinoma
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Interventional Arm A - HPV(+) | Experimental | De-escalation Radio(chemo)therapy - Level 1 | |
| Interventional Arm B - HPV(+) | Experimental | De-escalation Radio(chemo)therapy - Level 2 | |
| Observational Arm A - HPV(-) | Active Comparator | Standard Radio(chemo)therapy | |
| Observational Arm B - HPV(+) | Active Comparator | Standard Radio(chemo)therapy | |
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | rate of locoregional recurrences |
| Time Frame: | 24 months after end of treatment |
| Safety Issue: | |
| Description: | measured from the last day of treatment |
Secondary Outcome Measures
| Measure: | overall survival |
| Time Frame: | 60 months and 5 years after end of treatment |
| Safety Issue: | |
| Description: | measured from the last day of treatment |
| Measure: | acute toxicity |
| Time Frame: | 3 months after end of treatment |
| Safety Issue: | |
| 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. |
| Measure: | late toxicity |
| Time Frame: | 24 months after end of treatment |
| Safety Issue: | |
| Description: | The occurrence of late side effects will be recorded and documented based on CTCAE 4.0 after every follow-up visit. |
| Measure: | quality of life of cancer patients |
| Time Frame: | 24 months after end of treatment |
| Safety Issue: | |
| 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. |
| Measure: | quality of life - disease specific |
| Time Frame: | 24 months after end of treatment |
| Safety Issue: | |
| 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. |
| Measure: | rate of locoregional recurrences |
| Time Frame: | 5 years after end of treatment |
| Safety Issue: | |
| Description: | measured from the last day of treatment |
Details
| Phase: | N/A |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Technische Universität Dresden |
Trial Keywords
- Head and neck cancer
- Oropharyngeal cancer
- postoperative
- radiotherapy
- radiochemotherapy
- de-intensification
- HPV
Last Updated
March 9, 2021
