Comparative Effectiveness Trial of Transoral Head and Neck Surgery Followed by Adjuvant Radio(Chemo)Therapy Versus Primary Radiochemotherapy for Oropharyngeal Cancer

Phase 4

Active, not recruiting

• Conditions: Oropharyngeal Cancer
• Interventions: Procedure: Resection; Drug: Chemotherapy; Radiation: Radiotherapy; Procedure: Salvage neck dissection

• Registration Number: NCT03691441
• Lead Sponsor: Universitätsklinikum Hamburg-Eppendorf

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.

Study Timeline

• Study Start: 2018-01-05
• Study First Submitted: 2018-03-02
• Study First Submitted QC: 2018-09-28
• Study First Posted: 2018-10-01
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-15
• Last Update Posted: 2023-05-17
• Primary Completion: 2024-05-05
• Study Completion: 2024-05-05

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 280

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Adjuvant radio(-chemo)therapy/salvage neck dissection	Salvage neck dissection	* 6-7 weeks standard radiotherapy (IMRT-technique), start within 4 weeks after randomization * 70-72 Gy, SIB possible * Cisplatin 100 mg/m2 on days 1, 22, 43 or Cisplatin once weekly (30-40 mg/m2) on days 1, 8, 15, 22, 29, 36 or Mitomycin C 10 mg/m2 d1, 29 and 5-FU 600 mg/m2/day iv on days 1-5 or Cisplatin 20 mg/m² + 5-FU 600 mg/m²/day iv d 1-5 and 29-33 * +/- Salvage neck dissection 12±2 weeks after treatment
Adjuvant radio(-chemo)therapy/salvage neck dissection	Chemotherapy	* 6-7 weeks standard radiotherapy (IMRT-technique), start within 4 weeks after randomization * 70-72 Gy, SIB possible * Cisplatin 100 mg/m2 on days 1, 22, 43 or Cisplatin once weekly (30-40 mg/m2) on days 1, 8, 15, 22, 29, 36 or Mitomycin C 10 mg/m2 d1, 29 and 5-FU 600 mg/m2/day iv on days 1-5 or Cisplatin 20 mg/m² + 5-FU 600 mg/m²/day iv d 1-5 and 29-33 * +/- Salvage neck dissection 12±2 weeks after treatment
Resection/adjuvant radio(-chemo)therapy	Resection	* Transoral surgical resection within 4 weeks after randomization * Neck dissection can be performed during resection of the primary tumor or within 4 weeks after randomization * 6-7 weeks standard risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy according to arm B if necessary), start within 6 weeks post-surgery
Resection/adjuvant radio(-chemo)therapy	Radiotherapy	* Transoral surgical resection within 4 weeks after randomization * Neck dissection can be performed during resection of the primary tumor or within 4 weeks after randomization * 6-7 weeks standard risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy according to arm B if necessary), start within 6 weeks post-surgery
Adjuvant radio(-chemo)therapy/salvage neck dissection	Radiotherapy	* 6-7 weeks standard radiotherapy (IMRT-technique), start within 4 weeks after randomization * 70-72 Gy, SIB possible * Cisplatin 100 mg/m2 on days 1, 22, 43 or Cisplatin once weekly (30-40 mg/m2) on days 1, 8, 15, 22, 29, 36 or Mitomycin C 10 mg/m2 d1, 29 and 5-FU 600 mg/m2/day iv on days 1-5 or Cisplatin 20 mg/m² + 5-FU 600 mg/m²/day iv d 1-5 and 29-33 * +/- Salvage neck dissection 12±2 weeks after treatment
Resection/adjuvant radio(-chemo)therapy	Chemotherapy	* Transoral surgical resection within 4 weeks after randomization * Neck dissection can be performed during resection of the primary tumor or within 4 weeks after randomization * 6-7 weeks standard risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy according to arm B if necessary), start within 6 weeks post-surgery

Primary Outcome Measures

Name	Time	Method
Time to local or locoregional failure or death from any cause	Defined as time from randomization up to 36 month	The primary objective of this study is to evaluate the effectiveness of primary surgical versus non-surgical treatment of patients with locally advanced, but transorally resectable oropharyngeal cancer in terms of time to local or locoregional failure or death from any cause (LRF).

Secondary Outcome Measures

Name	Time	Method
Quality of life evaluated by patient	Until 3 years after randomization	CareQuality of life Questionnaires using EORTC QLQ-C30 both study arms
Cost-utility	Until 3 years after randomization	Cost-utility in both study armsusing Questionnaire Health Care Utilization and Productivity loss.
Cost-effectiveness	Until 3 years after randomization	Cost-effectiveness in both study arms using Questionnaire Health Utilization and Productivity loss.
Disease-free survival	Until 3 years after randomization	Disease-free survival (DFS) in both study arms. CT- Scans will be performed at month 3, month 6, 18, 30 and in case of suspicion of recurrence
Effectiveness in terms of morbidity	Until 3 years after randomization	Effectiveness in terms of morbidity (including swallowing function by MDADI Score) by late morbidity documentation in both study arms.
Overall survival	Until 3 years after randomization	Overall survival (OS) in both study arms, follow-up visits until the end of study
Effectiveness in terms of toxicity	Until 3 years after randomization	Effectiveness in terms of toxicity in both study arms. Monitoring of AE's/SAE's from randomization to 28 days after the last administration of IMP and/or 5 months after randomization in this trial

Trial Locations

Locations (20)

Berlin Charité; 🇩🇪 Berlin, Germany

Universitätsklinikum Hamburg Eppendorf; 🇩🇪 Hamburg, Germany

Universität des Saarlandes; 🇩🇪 Homburg, Saarland, Germany

Universitäts- HNO- Klinik Mannhein; 🇩🇪 Mannheim, Baden- Würtemberg, Germany

St. Vincentius- Kliniken Karlsruhe; 🇩🇪 Karlsruhe, Baden-Württemberg, Germany

Ruppiner Klinken GmbH; 🇩🇪 Neuruppin, Brandenburg, Germany

Universitätsklinikum Gießen; 🇩🇪 Gießen, Hessen, Germany

Philipps-Universität Marburg; 🇩🇪 Marburg, Hessen, Germany

Elbekliniken Stade- Buxtehude GmbH, Klinikum Stade und Klinik Dr. Hancken; 🇩🇪 Stade, Niedersachsen, Germany

Klinikum Wolfsburg; 🇩🇪 Wolfsburg, Niedersachsen, Germany

Kreiskliniken Gummersbach-Waldbröl GmbH Klinik Oberberg; 🇩🇪 Gummersbach, Nordrhein-Westfalen, Germany

Universitätsklinikum Köln; 🇩🇪 Köln, Nordrhein-Westfalen, Germany

Katholischen Krankenhaus Koblenz; 🇩🇪 Koblenz, Rheinland-Pfalz, Germany

Universitätsklinik Leipzig / Borna Sana Kliniken Leipziger Land; 🇩🇪 Leipzig, Sachsen, Germany

Universitätsklinikum Schleswig-Holstein Campus Lübeck; 🇩🇪 Lübeck, Schleswig- Holstein, Germany

Universitätsklinikum Jena; 🇩🇪 Jena, Thüringen, Germany

Helios Amper- Klinikum Dachau; 🇩🇪 Dachau, Bayern, Germany

Universitätsklinikum Frankfurt; 🇩🇪 Frankfurt, Hessen, Germany

Universitätsklinikum Ulm; 🇩🇪 Ulm, Baden-Württemberg, Germany

Klinikum Ernst von Bergmann gemeinnützige GmbH; 🇩🇪 Potsdam, Brandenburg, Germany