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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

Sponsor
Universitätsklinikum Hamburg-Eppendorf (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03691441
Collaborator
Charite University, Berlin, Germany (Other), University Medical Center Gießen and Marburg GmbH (Other), University Hospital Ulm (Other)
280
Enrollment
20
Locations
2
Arms
65
Anticipated Duration (Months)
14
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

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

Condition or Disease Intervention/Treatment Phase
  • Procedure: Resection
  • Radiation: Radiotherapy
  • Drug: Chemotherapy
  • Procedure: Salvage neck dissection
 Phase 4

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 Design

Study Type:
Interventional
Anticipated Enrollment :
280 participants
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.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)
Primary Purpose:
Treatment
Official Title:
Comparative Effectiveness Trial of Transoral Head and Neck Surgery Followed by Adjuvant Radio(Chemo)Therapy Versus Primary Radiochemotherapy for Oropharyngeal Cancer
Actual Study Start Date :
Jan 5, 2018
Anticipated Primary Completion Date :
Jun 5, 2023
Anticipated Study Completion Date :
Jun 5, 2023

Arms and Interventions

Arm Intervention/Treatment
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

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.
Other Names:
  • Transoral Surgery

    • 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.
    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

    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

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. Overall survival [Until 3 years after randomization]

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

    2. 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

    3. 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

    4. 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.

    5. Quality of life evaluated by patient [Until 3 years after randomization]

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

    6. Quality of life evaluated by patient [Until 3 years after randomization]

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

    7. Cost-utility [Until 3 years after randomization]

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

    8. Cost-effectiveness [Until 3 years after randomization]

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

    Other Outcome Measures

    1. Tertiary objectives include comparisons of treatment effects between HPV- Status [Up to 36 month]

      Subgroup analysis of HPV-positive and HPV-negative oropharynx carcinoma

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Universitäts- HNO- Klinik Mannhein Mannheim Baden- Würtemberg Germany 68167
    2 St. Vincentius- Kliniken Karlsruhe Karlsruhe Baden-Württemberg Germany 76135
    3 Universitätsklinikum Ulm Ulm Baden-Württemberg Germany 89075
    4 Helios Amper- Klinikum Dachau Dachau Bayern Germany 85221
    5 Ruppiner Klinken GmbH Neuruppin Brandenburg Germany 16816
    6 Klinikum Ernst von Bergmann gemeinnützige GmbH Potsdam Brandenburg Germany 14467
    7 Universitätsklinikum Frankfurt Frankfurt Hessen Germany 60590
    8 Universitätsklinikum Gießen Gießen Hessen Germany 35385
    9 Philipps-Universität Marburg Marburg Hessen Germany 35037
    10 Elbekliniken Stade- Buxtehude GmbH, Klinikum Stade und Klinik Dr. Hancken Stade Niedersachsen Germany 21682
    11 Klinikum Wolfsburg Wolfsburg Niedersachsen Germany 38440
    12 Kreiskliniken Gummersbach-Waldbröl GmbH Klinik Oberberg Gummersbach Nordrhein-Westfalen Germany 51643
    13 Universitätsklinikum Köln Köln Nordrhein-Westfalen Germany 50937
    14 Katholischen Krankenhaus Koblenz Koblenz Rheinland-Pfalz Germany 56073
    15 Universität des Saarlandes Homburg Saarland Germany 22421
    16 Universitätsklinik Leipzig / Borna Sana Kliniken Leipziger Land Leipzig Sachsen Germany 04103
    17 Universitätsklinikum Schleswig-Holstein Campus Lübeck Lübeck Schleswig- Holstein Germany 23538
    18 Universitätsklinikum Jena Jena Thüringen Germany 07757
    19 Berlin Charité Berlin Germany 13353
    20 Universitätsklinikum Hamburg Eppendorf Hamburg Germany 20246

    Sponsors and Collaborators

    • Universitätsklinikum Hamburg-Eppendorf
    • Charite University, Berlin, Germany
    • University Medical Center Gießen and Marburg GmbH
    • University Hospital Ulm

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Universitätsklinikum Hamburg-Eppendorf
    ClinicalTrials.gov Identifier:
    NCT03691441
    Other Study ID Numbers:
    • TopROC
    First Posted:
    Oct 1, 2018
    Last Update Posted:
    Dec 11, 2020
    Last Verified:
    Dec 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Universitätsklinikum Hamburg-Eppendorf
    locally advanced
    transorally resectable
    Additional relevant MeSH terms:
    Oropharyngeal Neoplasms

    Study Results

    No Results Posted as of Dec 11, 2020