Clinical Trials /

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

NCT03396718

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.

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

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

NameTypeDescriptionInterventions
Interventional Arm A - HPV(+)ExperimentalDe-escalation Radio(chemo)therapy - Level 1
    Interventional Arm B - HPV(+)ExperimentalDe-escalation Radio(chemo)therapy - Level 2
      Observational Arm A - HPV(-)Active ComparatorStandard Radio(chemo)therapy
        Observational Arm B - HPV(+)Active ComparatorStandard 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:
          
                    -  cumulative nicotine abuse > 30 packyears
          
                    -  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:Not yet recruiting
          Lead Sponsor:Technische Universität Dresden

          Trial Keywords

          • Head and neck cancer
          • Oropharyngeal cancer
          • postoperative
          • radiotherapy
          • radiochemotherapy
          • de-intensification
          • HPV

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