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

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Collaborators:

Information provided by (Responsible Party):

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Tracking Information

First Submitted Date ^ICMJE

March 2, 2018

First Posted Date ^ICMJE

October 1, 2018

Last Update Posted Date

October 1, 2018

Actual Study Start Date ^ICMJE

January 5, 2018

Estimated Primary Completion Date

June 5, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Time to local or locoregional failure or death from any cause[ Time Frame: 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).

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

Overall survival[ Time Frame: Until 3 years after randomization ]
Overall survival (OS) in both study arms, follow-up visits until the end of study
Disease-free survival[ Time Frame: 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 toxicity[ Time Frame: 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
Effectiveness in terms of morbidity[ Time Frame: Until 3 years after randomization ]
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[ Time Frame: Until 3 years after randomization ]
Quality of life Questionnaires using QLQ H&N-43 in both study arms
Quality of life evaluated by patient[ Time Frame: Until 3 years after randomization ]
CareQuality of life Questionnaires using EORTC QLQ-C30 both study arms
Cost-utility[ Time Frame: Until 3 years after randomization ]
Cost-utility in both study armsusing Questionnaire Health Care Utilization and Productivity loss.
Cost-effectiveness[ Time Frame: Until 3 years after randomization ]
Cost-effectiveness in both study arms using Questionnaire Health Utilization and Productivity loss.

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

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 Type ^ICMJE

Interventional

Study Phase

Phase 4

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Masking: Interventional
Masking Description:
Primary Purpose: Treatment

Condition ^ICMJE

Intervention ^ICMJE

Procedure: Resection
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.
Radiation: Radiotherapy
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
Drug: Chemotherapy
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.
Procedure: Salvage neck dissection
+/- Salvage neck dissection 12±2 weeks after treatment

Study Arms

Experimental: Resection/adjuvant radio(-chemo)therapy
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
Active Comparator: Adjuvant radio(-chemo)therapy/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

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

280

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

June 5, 2023

Estimated Primary Completion Date

June 5, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Sex/Gender

Sexes Eligible for Study:

All

Ages

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

Germany

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Responsible Party

，

Study Sponsor ^ICMJE

Universitätsklinikum Hamburg-Eppendorf

Collaborators ^ICMJE

Investigators ^ICMJE

Principal Investigator: Chia-Jung Busch, PD Dr. Universitätsklinikum Hamburg-Eppendorf

PRS Account

Verification Date

September 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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