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

Primary Purpose

Oropharyngeal Cancer

Status

Active

Phase

Phase 4

Locations

Germany

Study Type

Interventional

Intervention

Resection

Radiotherapy

Chemotherapy

Salvage neck dissection

About this trial

This is an interventional treatment trial for Oropharyngeal Cancer focused on measuring locally advanced, transorally resectable

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Universitäts- HNO- Klinik Mannhein
St. Vincentius- Kliniken Karlsruhe
Universitätsklinikum Ulm
Helios Amper- Klinikum Dachau
Ruppiner Klinken GmbH
Klinikum Ernst von Bergmann gemeinnützige GmbH
Universitätsklinikum Frankfurt
Universitätsklinikum Gießen
Philipps-Universität Marburg
Elbekliniken Stade- Buxtehude GmbH, Klinikum Stade und Klinik Dr. Hancken
Klinikum Wolfsburg
Kreiskliniken Gummersbach-Waldbröl GmbH Klinik Oberberg
Universitätsklinikum Köln
Katholischen Krankenhaus Koblenz
Universität des Saarlandes
Universitätsklinik Leipzig / Borna Sana Kliniken Leipziger Land
Universitätsklinikum Schleswig-Holstein Campus Lübeck
Universitätsklinikum Jena
Berlin Charité
Universitätsklinikum Hamburg Eppendorf

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Resection/adjuvant radio(-chemo)therapy

Adjuvant radio(-chemo)therapy/salvage neck dissection

Arm Description

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

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Overall survival

Overall survival (OS) in both study arms, follow-up visits until the end of study

Disease-free survival

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 toxicity

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

Effectiveness in terms of morbidity

Effectiveness in terms of morbidity (including swallowing function by MDADI Score) by late morbidity documentation in both study arms.

Quality of life evaluated by patient

Quality of life Questionnaires using QLQ H&N-43 in both study arms

Quality of life evaluated by patient

CareQuality of life Questionnaires using EORTC QLQ-C30 both study arms

Cost-utility

Cost-utility in both study armsusing Questionnaire Health Care Utilization and Productivity loss.

Cost-effectiveness

Cost-effectiveness in both study arms using Questionnaire Health Utilization and Productivity loss.

Full Information

NCT ID

NCT03691441

First Posted

March 2, 2018

Last Updated

May 15, 2023

Sponsor

Universitätsklinikum Hamburg-Eppendorf

Collaborators

Charite University, Berlin, Germany, University Medical Center Gießen and Marburg GmbH, University Hospital Ulm

1. Study Identification

Unique Protocol Identification Number

NCT03691441

Brief Title

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

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

January 5, 2018 (Actual)

Primary Completion Date

May 5, 2024 (Anticipated)

Study Completion Date

May 5, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Universitätsklinikum Hamburg-Eppendorf

Collaborators

Charite University, Berlin, Germany, University Medical Center Gießen and Marburg GmbH, University Hospital Ulm

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Oropharyngeal Cancer

Keywords

locally advanced, transorally resectable

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

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.

Masking

None (Open Label)

Allocation

Randomized

Enrollment

280 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Resection/adjuvant radio(-chemo)therapy

Arm Type

Experimental

Arm Description

Arm Title

Adjuvant radio(-chemo)therapy/salvage neck dissection

Arm Type

Active Comparator

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Resection

Other Intervention Name(s)

Transoral Surgery

Intervention Description

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.

Intervention Type

Radiation

Intervention Name(s)

Radiotherapy

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Chemotherapy

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Salvage neck dissection

Intervention Description

+/- Salvage neck dissection 12±2 weeks after treatment

Primary Outcome Measure Information:

Title

Time to local or locoregional failure or death from any cause

Description

Time Frame

Defined as time from randomization up to 36 month

Secondary Outcome Measure Information:

Title

Overall survival

Description

Overall survival (OS) in both study arms, follow-up visits until the end of study

Time Frame