Study Assessing The “Best of” Radiotherapy vs the “Best of” Surgery in Patients With Oropharyngeal Carcinoma

Brief Title

Study Assessing The "Best of" Radiotherapy vs the "Best of" Surgery in Patients With Oropharyngeal Carcinoma

Official Title

Phase III Study Assessing the "Best of" Radiotherapy Compared to the "Best of" Surgery (Trans-oral Surgery (TOS)) in Patients With T1-T2, N0-N1 Oropharyngeal, Supraglottic Carcinoma and With T1, N0 Hypopharyngeal Carcinoma

Brief Summary

      Oropharyngeal Squamous Cell Carcinoma (OPSCC) arises in the soft palate, tonsils, base of
      tongue, pharyngeal wall, and the vallecula. Most of the patients with early stage OPSCC are
      usually cured. Treatment of early stage OPSCC can be successfully achieved with primary
      surgery including neck dissection, as indicated, or with definitive radiotherapy. The current
      standard treatment for OPSCC is therefore based on either surgery and/or radiotherapy, both
      associated with comparable, high tumor control rates but with different side effects profiles
      and technical constraints.

      In order to decrease the potential morbidity of surgery, transoral approaches have been
      developed within the last decades, including transoral robotic surgery (TORS), transoral
      laser microsurgery (TLM) or conventional transoral techniques. On the other hand, patients
      with head and neck cancer treated with IMRT experienced significant improvements in cause
      specific survival (CSS) compared with patients treated with non-IMRT techniques thus
      suggesting that IMRT may be beneficial in terms of patient's outcomes and toxicity profile.
      It is as yet unclear however, which one of the new techniques is superior to the other in
      terms of function preservation. Given that the functional outcome of most importance is
      swallowing function, the preservation of swallowing is thus of major importance.

      The main objective of the study is to assess and compare the patient-reported swallowing
      function over the first year after randomization to either IMRT or TOS among patients with
      early stage OPSCC, SGSCC, and HPSCC.
    

Detailed Description

      Eligible patients will be randomized 1 to 1 to surgery (Arm 1) or radiotherapy (Arm 2).

      ARM 1: Surgery

      Trans-oral surgery (any trans-oral approach such as trans-oral laser microsurgery
      conventional trans-oral surgery or trans-oral robotic surgery) will be applied to all
      patients in this arm.

      A surgical margin is defined to be clear (R0), if found to be >/=3mm in the final specimen
      (except deep margin for tonsillar resection, that is either R1 or R0), is defined to be
      close, if 1-<3mm, and considered to be involved (R1), if <1mm in the final specimen. Clearly
      defined marginal biopsies are required for each TOS-technique. Trans-oral re-resections are
      required in case of R1 or close-margin to convert the patient to an R0-status.Postoperative
      RT or chemo-RT will be given within 5-6 weeks of surgery in case of positive.

      ARM 2: Radiotherapy

      Intensity modulated radiation therapy (IMRT) with Simultaneous integrated boost (SIB) will be
      applied to all patients in this arm. PTV prescription to tumor and high risk areas will be
      delivered daily for 5 days per week to a total dose of 66-70Gy in 2 Gy/fraction over 6 weeks,
      elective/prophylactic mucosal and nodal areas will receive a total dose of 54.25- 54.45 Gy in
      33-35 fractions of 1.55-1.65 Gy over 6 weeks.
    


Study Type

Interventional


Primary Outcome

Change in the MD Anderson Dysphagia Inventory (MDADI) score


Condition

Oropharyngeal Cancer

Intervention

Intensity-Modulated Radiation Therapy (IMRT)

Study Arms / Comparison Groups

 Intensity-Modulated Radiation Therapy (IMRT)
Description:  PTV prescription to tumor and high risk areas will be delivered daily for 5 days per week to a total dose of 66-70Gy in 2 Gy/fraction over 6 weeks, elective/prophylactic mucosal and nodal areas will receive a total dose of 54.25- 54.45 Gy in 33-35 fractions of 1.55-1.65 Gy over 6 weeks.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Radiation

Estimated Enrollment

112

Start Date

November 27, 2017

Completion Date

January 2028

Primary Completion Date

December 2022

Eligibility Criteria

        Main Inclusion Criteria:

          -  OPSCC in one of the following sub-sites: base of tongue, lateral pharyngeal wall,
             tonsil, glosso-tonsillar sulcus, vallecula or SGSCC in one or more of the following
             sub-sites: epiglottis, aryepiglottic fold, false cord or HPSCC in one or more of the
             following subsites: Lateral and medial wall of piriform sinus (sub-sites are defined
             as lateral (lateral pharyngeal wall, tonsil, glosso-tonsillar sulcus, lateral piriform
             sinus) vs. central lesions (base of tongue, vallecula, all supraglottic sites, medial
             wall of piriform sinus))

          -  TNM stage I-III (7th AJCC classification): T1 or T2, N0 or T1 or T2, N1 with one
             single neck node ≤ 3cm without radiographic signs of extracapsular extension (ECE),
             M0;

          -  TNM stage I for HPSCC: T1, N0, M0. ;

          -  Within 2 weeks before randomization, assessment by a Multi-Disciplinary Team (MDT)
             composed of at least a head and neck/ENT surgeon, oncologist, radiologist,
             radiotherapist, and pathologist of the treatment naïve patient and suitable for either
             TOS or IMRT based on:

          -  CT with contrast and/or MRI done within 4 weeks prior to randomization Note: Repeat
             contrast enhanced CT and/or MRI or US 1 week or less prior to randomization in case of
             suspicious nodes <1cm on initial scan if per local practice

          -  Pan-endoscopy with assessment of trans-oral exposure for resection.

          -  peri-nodal infiltration either via CT-scan or MRI.

          -  Age 18 and older; Age 18 to 70 for SGSCC

          -  ECOG Performance status ≤ 2;

          -  Availability of biological material for HPV/p16 testing for OPSCCs

          -  Study information and Informed consent discussed by the surgeon and radio-oncologist
             and signed by the patient.

          -  Within 2 weeks prior randomization:

          -  Baseline MDADI score available;

          -  Adequate bone marrow function as demonstrated by neutrophils count > 1,5 109 /L ,
             platelets count > 75 109 /L, WBC≥ 3.0 109 /L;

          -  Prothrombin time (PT) with an international normalized ratio (INR) ≤ 1.2

          -  Partial thromboplastin time (PTT) ≤ 1.2 times ULN

          -  Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy
             test no more than 72 hours prior to randomization.

          -  Patients of childbearing / reproductive potential should agree to use adequate birth
             control measures for 3 months, especially if they will undergo any radiotherapy
             treatment at any time during the study. A highly effective method of birth control is
             defined as those which result in low failure rate (i.e. less than 1% per year) when
             used consistently and correctly.

        Main Exclusion Criteria:

          -  Any previous anti-cancer therapy for HNSCC (surgery, chemo-, or radiotherapy or
             molecular targeted therapy);

          -  Any active malignancy (other than non-melanoma skin cancer or localized cervical
             cancer or localized and presumed cured prostatic cancer) within the last 5 years with
             ongoing systemic treatment

          -  Cancer in contact with the internal and/or common carotid artery

          -  Extension of OPSCC across the midline of the base-of-tongue

          -  Arytenoid involvement in case of SGSCC

          -  Infiltration of apex for piriform sinus in case of HPSCC

          -  Cancer originating from the soft palate or posterior pharyngeal wall

          -  Requirement of a reconstruction with a free or regional flap (i.e. involvement of >50%
             of the soft palate)

          -  Pre-existing dysphagia not related to the oropharyngeal cancer or diagnostic biopsies

          -  Any psychological, cognitive, familial, sociological or geographical condition
             potentially hampering compliance with the study protocol, completion of patient
             reported measures and follow-up schedule; those conditions should be discussed with
             the patient before registration in the trial
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Christian Simon, +32 2 774 16 11, [email protected]

Location Countries

Belgium

Location Countries

Belgium

Administrative Informations


NCT ID

NCT02984410

Organization ID

EORTC-1420-HNCG-ROG


Responsible Party

Sponsor

Study Sponsor

European Organisation for Research and Treatment of Cancer - EORTC


Study Sponsor

Christian Simon, Study Chair, Centre Hospitalier Universitaire Vaudois


Verification Date

May 2021