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

Oropharyngeal Cancer Clinical Trial

— Best Of  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02984410
• Other study ID #: EORTC-1420-HNCG-ROG
• Status: Recruiting
• Phase: N/A
• Start date: November 27, 2017
• Est. completion date: September 2029

Study information

• Verified date: February 2023
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: EORTC HQ
• Phone: +32 2 774 16 11
• Email: eortc[@]eortc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 112
• Est. completion date: September 2029
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Hypopharyngeal Squamous Cell Carcinoma
• Oropharyngeal Cancer
• Oropharyngeal Neoplasms
• Squamous Cell Carcinoma of Head and Neck
• Supraglottic Squamous Cell Carcinoma

Intervention

Radiation:
• Intensity-Modulated Radiation Therapy (IMRT)
IMRT (Simultaneous Integrated Boost (SIB) and accelerated regimen) with selective neck node dissection

Procedure:
• Trans Oral Surgery (TOS)
TOS (Trans Oral Laser Microsurgery (TLM), Trans Oral Robotic Surgery (TORS), conventional) with selective neck node dissection

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Institut Jules Bordet-Hopital Universitaire ULB	Brussels
Belgium	U.Z. Leuven - Campus Gasthuisberg	Leuven
Belgium	CHU-UCL Namur - CHU Mont Godinne	Namur	Yvoir
France	Hopitaux Universitaires de Strasbourg - Hautepierre	Strasbourg
Germany	Universitaetklinikum Halle - Martin Luther Universitaet	Halle
Germany	Universitaets Krankenhaus Eppendorf - UKE - University Cancer Center	Hamburg
Germany	Universitaetsklinikum Jena	Jena
Germany	Universitaetsklinikum Koeln	Koeln
Germany	Staedtisches Klinikum Leipzig - Klinikum St Georg	Leipzig
Germany	Universitaetsklinikum Leipzig	Leipzig
Germany	Klinikum Rechts der isar Der Technische Universitaet Muenchen	Muenchen
Germany	Universitaetsklinikum Tuebingen- Crona Kliniken	Tübingen
Germany	Universitaetsklinikum Ulm-Michelsberg-HNO	Ulm
Italy	Istituto Clinico Humanitas	Milan
Italy	Istituto Europeo di Oncologia	Milan
Poland	The Great Poland Cancer Centre	Poznan
Spain	Hospital Universitario Donostia	Barcelona
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Central De Asturias	Oviedo
Switzerland	Universitaetsspital Basel	Basel
Switzerland	Inselspital	Bern
Switzerland	Centre Hospitalier Universitaire Vaudois - Lausanne	Lausanne
Switzerland	UniversitaetsSpital Zurich - Klinik fur Ohren, Hals und Gesichtschirurgie	Zürich
United Kingdom	University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre	Bristol
United Kingdom	Cambridge University Hospital NHS - Addenbrookes Hospital	Cambridge
United Kingdom	Cardiff and Vale University Health Board - University Hospital of Wales	Cardiff
United Kingdom	Hull and East Yorkshire Hospitals NHS Trust - Castle Hill Hospital	Cottingham
United Kingdom	Aintree University Hospital NHS Trust	Liverpool
United Kingdom	Guy's and St Thomas' NHS Foundation trust - Guy s and St Thomas' NHS - Guy's Hospital	London
United Kingdom	Imperial College Healthcare NHS Trust - Charing Cross Hospital	London
United Kingdom	South Tees Hospitals NHS Foundation Trust - The James Cook University Hospital	Middlesbrough

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Italy,  Poland,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the MD Anderson Dysphagia Inventory (MDADI) score		at 4.5 and 12 months after randomization