Clinical trial NCT03691441: Comparative Effectiveness Trial of Transoral Head and Neck Surgery Followed by Adjuvant Radio(Chemo)Therapy Versus Primary Radiochemotherapy for Oropharyngeal Cancer
Official title: Comparative Effectiveness Trial of Transoral Head and Neck Surgery Followed by Adjuvant Radio(Chemo)Therapy Versus Primary Radiochemotherapy for Oropharyngeal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Oropharyngeal Cancer
Keywords: locally advanced
transorally resectable
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: Charite University, Berlin, Germany
name: University Medical Center Gießen and Marburg GmbH
name: University Hospital Ulm
First posted: 2018-10-01
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, two-arm, open label, multicenter, randomized, controlled comparative effectiveness study.

The trial is based on an event-driven design: the final analysis will be performed when all events have been observed or the study was terminated at one of the interim analyses.
Primary purpose: TREATMENT

Brief summary: Comparative Effectiveness Trial of Transoral Head and Neck Surgery followed by adjuvant Radio(chemo)therapy versus primary Radiochemotherapy for Oropharyngeal Cancer

Detailed description: This trial investigates the effectiveness of transoral head and neck surgery (TOS) for locally advanced, but transorally resectable oropharyngeal cancer followed by risk-adapted adjuvant therapy versus primary radiochemotherapy (definitive chemoradiotherapy, CRTX). Both treatments are internationally accepted standards. The choice of the treatment strategy depends on the preference of the responsible attending physician and on the country of residence. Internationally, mostly definitive chemoradiotherapy is regarded as the standard of care for oropharyngeal cancer. In Germany, however, transoral surgical resection is also well established and commonly practiced. The key question therefore is whether one of the two therapies is more effective than the other in clinical daily routine under the given conditions of our health care system and with a realistic, non-ideal patient cohort. For this reason, a comparative effectiveness research (CER) concept will be applied in this setting. The aim of this trial is primarily to show a superiority of the surgical approach in terms of local and locoregional control and secondarily to compare functional outcome and quality of life.

Eligibility criteria: Inclusion Criteria:

* Histologically proven SCC of the oropharynx; T1, N2a-c, M0; T2, N1-2c, M0; T3, N0-2c, M0, with only amendable to transoral resection)
* Primary tumor must be resectable through transoral approach
* p16 immunohistochemitry by local pathology or FFPE tissue must be available for central HPV diagnostic
* Written and signed informed consent
* Briefing through surgeon and radiation oncologist
* ECOG PS ≥2, Karnofsky PS ≥ 60 %
* Age ≥ 18
* Curative treatment intent
* Adequate bone marrow function: leucocytes \> 3.0 x 109/L, neutrophils \> 1.5 x 109/L, platelets \> 80 x 109/L, hemoglobin \> 9.5 g/dL
* Adequate liver function: Bilirubin \< 2.0 g/dL, SGOT, SGPT, \< 3 x ULN
* If of childbearing potential, willingness to use effective contraceptive method for the study duration and 2 months post-dosing.
* dental examination and appropriate dental therapy if needed prior to Confidential TopROC 2017_03_24 Version 1.0 Seite 15 von 124 beginning of radiotherapy
* Nutritional evaluation prior to initiation of therapy and optional prophylactic gastrostomy (PEG) tube placement

Exclusion Criteria:

* Prior invasive malignancy except controlled skin cancer or carcinoma in situ of cervix
* Unknown primary (CUP), nasopharynx, hypopharynx, laryngeal or salivary gland cancer
* Metastatic disease
* Serious co-morbidity, e.g. high-grade carotid artery stenosis, congestive heart failure NYHA grade 3 and 4, liver cirrhosis CHILD C
* Hemoglobin level \<9.5g/dl within 4 weeks before randomization
* Pregnancy or lactation
* Women of child-bearing potential with unclear contraception
* Previous treatment with chemotherapy, radiotherapy, EGFR-targeting agents or surgery exceeding biopsy in head and neck
* Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study screening
* Social situations that limit compliance with study requirements or patients with an unstable condition (e.g., psychiatric disorder, a recent history of drug or alcohol abuse, interfering with study compliance, within 6 months prior to screening) or otherwise thought to be unreliable or incapable of complying with the requirements of the protocol
* Patients institutionalized by official means or court order
* Deficient

Primary outcomes:
measure: Time to local or locoregional failure or death from any cause
timeFrame: Defined as time from randomization up to 36 month
Secondary outcomes:
measure: Overall survival
timeFrame: Until 3 years after randomization
measure: Disease-free survival
timeFrame: Until 3 years after randomization
measure: Effectiveness in terms of toxicity
timeFrame: Until 3 years after randomization
measure: Effectiveness in terms of morbidity
timeFrame: Until 3 years after randomization
measure: Quality of life evaluated by patient
timeFrame: Until 3 years after randomization
measure: Quality of life evaluated by patient
timeFrame: Until 3 years after randomization
measure: Cost-utility
timeFrame: Until 3 years after randomization
measure: Cost-effectiveness
timeFrame: Until 3 years after randomization
Other outcomes:
measure: Tertiary objectives include comparisons of treatment effects between HPV- Status
timeFrame: Up to 36 month
Locations:
city: Mannheim
country: Germany
facility: Universitäts- HNO- Klinik Mannhein
state: Baden- Würtemberg
city: Karlsruhe
country: Germany
facility: St. Vincentius- Kliniken Karlsruhe
state: Baden-Württemberg
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-Württemberg
city: Dachau
country: Germany
facility: Helios Amper- Klinikum Dachau
state: Bayern
city: Neuruppin
country: Germany
facility: Ruppiner Klinken GmbH
state: Brandenburg
city: Potsdam
country: Germany
facility: Klinikum Ernst von Bergmann gemeinnützige GmbH
state: Brandenburg
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
state: Hessen
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen
state: Hessen
city: Marburg
country: Germany
facility: Philipps-Universität Marburg
state: Hessen
city: Stade
country: Germany
facility: Elbekliniken Stade- Buxtehude GmbH, Klinikum Stade und Klinik Dr. Hancken
state: Niedersachsen
city: Wolfsburg
country: Germany
facility: Klinikum Wolfsburg
state: Niedersachsen
city: Gummersbach
country: Germany
facility: Kreiskliniken Gummersbach-Waldbröl GmbH Klinik Oberberg
state: Nordrhein-Westfalen
city: Köln
country: Germany
facility: Universitätsklinikum Köln
state: Nordrhein-Westfalen
city: Koblenz
country: Germany
facility: Katholischen Krankenhaus Koblenz
state: Rheinland-Pfalz
city: Homburg
country: Germany
facility: Universität des Saarlandes
state: Saarland
city: Leipzig
country: Germany
facility: Universitätsklinik Leipzig / Borna Sana Kliniken Leipziger Land
state: Sachsen
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Campus Lübeck
state: Schleswig- Holstein
city: Jena
country: Germany
facility: Universitätsklinikum Jena
state: Thüringen
city: Berlin
country: Germany
facility: Berlin Charité
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf
Study officials:
affiliation: Universitätsklinikum Hamburg-Eppendorf
name: Chia-Jung Busch, PD Dr.
role: PRINCIPAL_INVESTIGATOR
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