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

Universitätsklinikum Hamburg-Eppendorf280 enrolled

Overview

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

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

280

Conditions

Oropharyngeal Cancer

Interventions

ResectionPROCEDURE

Definitive surgery should generally be performed within 2 weeks, but not more than 4 weeks after randomization. The appropriately indicated neck dissection(s) may be performed either prior to, during the same session, or within 2 weeks after the resection of the primary tumor, but not later than 4 weeks following randomization. The primary tumor is to be resected with clear margins (R0) and en bloc in all cases. Frozen section assessment must be routinely and readily available.

RadiotherapyRADIATION

6-7 weeks standard risk-adapted adjuvant radiotherapy 56-66 Gy, start within 6 weeks post-surgery Arm B: 6-7 weeks standard radiotherapy (IMRT-technique), start within 4 weeks after randomization, 70-72 Gy, SIB possible

ChemotherapyDRUG

The investigational medicinal product (IMP) are the chemotherapeutical drugs Cisplatin, Mitomycin C and 5-FU. According to local routine, chemotherapy protocols as listed in study protocol should be used.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (20)

Universitäts- HNO- Klinik Mannhein

Mannheim, Baden- Würtemberg, Germany

Outcomes

Primary Outcomes

Time to local or locoregional failure or death from any cause

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).

Time frame: Defined as time from randomization up to 36 month