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.
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
- Head and neck therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this study is the MDADI score reported by the patient
at 12 months after randomization.
• The MDADI scale is composed of 19 items: Emotional (6 questions), Functional
(5 questions), Physical (8 questions) and the total MDADI score ranges from 20
(extremely low functioning) to 100 (high functioning).
• The study is powered to test the treatment difference at the 12 months* time
point.
Secondary outcome
Patient-reported MDADI at 4.5, 6 and 9 months
• Response after study treatment (measured at 6 months after randomization)
• Recurrence-free survival after complete response (CR)
• Local, regional, loco-regional and distant tumor control after CR
• Overall, disease specific and event free survival
• Second cancer
• Functional and HRQOL measures (PSS-HN, 100 ml swallow test, feeding tube use,
EORTC QLQ-C30 and H&N43)
Other secondary endpoints involve these same evaluations up to 5 years.
In general, clinical evaluation, pan-endoscopy with biopsy if indicated,
imaging scans taken at 6 months after randomization and evaluation of the MDT
shall be performed during the treatment and follow-up periods to evaluate
recurrence or progression. In the Best of Study, methods and schedule of follow
up are based on the NCCN guidelines as of 2016.
Background summary
Oropharyngeal Squamous Cell Carcinoma (OPSCC) arises in the soft palate,
tonsils, base of tongue, pharyngeal wall, and the vallecula. The oropharynx is
the posterior continuation of the oral cavity extending from the palate
superiorly to the level of hyoid bone inferiorly. It is subdivided into the:
• lateral wall: palatine tonsil, tonsillar fossae and pillars
• anterior wall: base of tongue and vallecula
• superior wall: soft palate and uvula
• posterior pharyngeal wall
It is a relatively uncommon malignancy with approximately 123,000 cases
diagnosed worldwide each year and about 79,000 deaths. The incidence of OPSCC
is rapidly increasing, associated with rising rates of oral infection with the
human papillomavirus (HPV). Regardless the HPV status, early stage OPSCC has an
average 5-year survival rate of over 80%. 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.
Several retrospective studies have independently shown comparable oncologic
outcomes from TOS as compared with external beam radiation. However, these
studies rely on historical data affected by selection bias, even in matched
cohort analysis. Nevertheless, disease specific survival (DSS) seems to be
invariably comparable between the 2 treatment modalities. The most recent
meta-analysis on early stage OPSCC reported a 5 years DSS of 90.4% (95%
Confidence Interval (CI): 85.6 - 95.2%) in the radiotherapy group and 89.6%
(95% CI: 81.8 - 97.3%) in the trans*oral surgery (TOS) group (Evidence Level
Class IV). The quality of the studies was similar in both groups. Equivalent
prognostic rates were reported in other studies.
Moreover, a literature review has been recently published comparing trans*oral
robotic surgery (TORS) with radiation therapy for T1 and T2 OPSCC. The analysis
performed within this study suggests that TOS was as effective as radiotherapy
for the treatment of early OPSCC in terms of oncological outcome (2-year
overall survival ranged from 84% to 96% for Intensity-Modulated Radiation
Therapy (IMRT) and from 82% to 94% for TORS).
Supra-glottic squamous cell cancer (SGSCC) is a second relatively uncommon
malignancy. As opposed to OPSCC the percentage of HPV-positive disease in this
location is negligible. According to current guidelines treatment for early
stage (stage I and III) consists of either radiation therapy only or organ
preservation surgery with similar oncological outcome ranging between 68% - 81%
DSS at 5 years.
Finally, also hypopharyngeal cancer is a very rare disease. Current treatment
guidelines recommend either surgery or radiation-only for T1 and T2 N0 cancers.
The current standard treatment for early stage OPSCC and SGSCC is therefore
based on either surgery or radiotherapy, both associated with comparable, high
tumor control rates but with different side effect profiles and technical
constraints. Radiotherapy and surgery are thus currently considered equivalent
based on similar cancer control rates so that treatment choice is
center-dependent.
With the advancements in the field of head and neck cancers novel strategies
have been developed that allow a more targeted approach to the cure of early
stage OPSCC, and SGSCC. These techniques that have been developed in parallel
in the RT and surgical fields have led to a significant reduction of
treatment-related morbidity, whilst preserving excellent oncological control.
The choice between these two treatment options is generally based on the
experience accumulated in each institution but not based on level 1 evidence.
Only a prospective randomized trial will be able to answer the question about
true functional equivalence of the two treatment modalities for these diseases
and shed light onto the question, which one of the modalities will provide
better functional outcome.
The trial will therefore identify a new standard of care for the majority of
early-stage head and neck cancer based on the most optimal function
preservation, whilst assuring an excellent oncological control rate as
demonstrated by previous meta-analysis.
Study objective
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.
Study design
This is an open-label, investigator initiated, multicenter, randomized phase
III study assessing and comparing the swallowing function after surgery (TOS)
versus radiotherapy (IMRT) in patients with early stage squamous cell carcinoma
of the oropharynx, supraglottis and hypopharynx.
Intervention
Eligible patients will be randomized 1 to 1 to TOS (Arm 1) or IMRT (Arm 2),
stratifying for tumor localization (lateral lesions: Lateral wall, tonsil,
glosso-tonsillar sulcus, lateral piriform sinus; central lesions: base of
tongue, vallecula, supraglottis, medial piriform sinus), N stage (T1/2N0 vs
T1/T2N1), MDADI score at baseline (below and above 67.0 points) and country.
Study burden and risks
The present study compares two standard treatments, in which the swallowing
function of patients is measured a few times more extensively by means of
questionnaires.
The follow-up frequency proposed in the study compared to the regular
oncological follow-up is not significantly higher than the frequency as
proposed in the national guideline. Participants are asked to complete
questionnaires, but the absolute burden of this is low.
Although the burden for the patients is manageable, the profit for patients is
also relatively limited. No difference in survival is expected, for example.
The questionnaires and the additional studies focus on the swallowing function.
It is known that swallowing has a major impact on the quality of life. More
accurate follow-up may lead to an earlier determination of a possible
swallowing problem. Whatever makes it possible to do something about it.
Avenue E. Mounier 83, BTE 11
Brussels 1200
BE
Avenue E. Mounier 83, BTE 11
Brussels 1200
BE
Listed location countries
Age
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 wall of piriform sinus) vs. central lesions
(base of tongue, vallecula, all supraglottic sites, medial wall of piriform
sinus))
• TNM stage I-III (7th AJCC classification) for OPSCC and SGSCC: 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, medical oncologist,
radiologist, radiotherapist, and pathologist of the treatment naïve patient and
suitable for either TOS or IMRT based on:
• Contrast enhanced CT and/or MRI done within 4 weeks prior to randomization
• Repeat contrast enhanced CT and/or MRI or US 1 week or less prior to
enrollment in case of suspicious nodes <1cm on initial scan if per local
practice
• Panendoscopy with assessment of trans-oral exposure for resection.
• peri-nodal infiltration either via CT-scan or MRI.
• ECOG Performance status <= 2;
• Availability of biological material for HPV/p16 testing for OPSCCs
• Age 18 and older; Age 18 to 70 for SGSCC
• 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 6 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.
Exclusion criteria
Any previous anti-cancer therapy for HNSCC (surgery, chemo, radiotherapy or
molecularly 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
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02984410 |
| CCMO | NL77741.029.21 |