AzTrials
AzTrials

Oropharyngeal CancerPhase 4NCT03691441

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

A Phase 4 study testing Resection, Radiotherapy and Chemotherapy in people with Oropharyngeal Cancer, run by Universitätsklinikum Hamburg-Eppendorf at 20 sites in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Oropharyngeal Cancer
What is being tested?
Resection, Radiotherapy and Chemotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
280 participants
Where
20 sitesGermany
Study dates
5 Jan 2018to 5 May 2024
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 %
Show all 13Show fewer
  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

Germany20 sites

  • Berlin Charité

    Berlin, 13353

  • Universitätsklinikum Köln

    Cologne, North Rhine-Westphalia, 50937

  • Helios Amper- Klinikum Dachau

    Dachau, Bavaria, 85221

  • Universitätsklinikum Frankfurt

    Frankfurt am Main, Hesse, 60590

  • Universitätsklinikum Gießen

    Giessen, Hesse, 35385

  • Kreiskliniken Gummersbach-Waldbröl GmbH Klinik Oberberg

    Gummersbach, North Rhine-Westphalia, 51643

  • Universitätsklinikum Hamburg Eppendorf

    Hamburg, 20246

  • Universität des Saarlandes

    Homburg, Saarland, 22421

  • Universitätsklinikum Jena

    Jena, Thuringia, 07757

  • St. Vincentius- Kliniken Karlsruhe

    Karlsruhe, Baden-Wurttemberg, 76135

  • Katholischen Krankenhaus Koblenz

    Koblenz, Rhineland-Palatinate, 56073

  • Universitätsklinik Leipzig / Borna Sana Kliniken Leipziger Land

    Leipzig, Saxony, 04103

  • Universitätsklinikum Schleswig-Holstein Campus Lübeck

    Lübeck, Schleswig-Holstein, 23538

  • Universitäts- HNO- Klinik Mannhein

    Mannheim, Baden- Würtemberg, 68167

  • Philipps-Universität Marburg

    Marburg, Hesse, 35037

  • Ruppiner Klinken GmbH

    Neuruppin, Brandenburg, 16816

  • Klinikum Ernst von Bergmann gemeinnützige GmbH

    Potsdam, Brandenburg, 14467

  • Elbekliniken Stade- Buxtehude GmbH, Klinikum Stade und Klinik Dr. Hancken

    Stade, Lower Saxony, 21682

  • Universitätsklinikum Ulm

    Ulm, Baden-Wurttemberg, 89075

  • Klinikum Wolfsburg

    Wolfsburg, Lower Saxony, 38440

Other trials in Germany

About this study

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

Read the 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.

Being tested
Resection, Radiotherapy, Chemotherapy, Salvage neck dissection
Keywords
locally advanced, transorally resectable
Medical subject headings
Oropharyngeal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ResectionProcedure or surgery

    Also called Transoral Surgery

    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.

  • Salvage neck dissectionProcedure or surgery

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

Study groups in NCT03691441
Study groupRoleWhat they receive
Resection/adjuvant radio(-chemo)therapyExperimental* 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
Receives: Procedure: Resection; Radiation: Radiotherapy; Drug: Chemotherapy
Adjuvant radio(-chemo)therapy/salvage neck dissectionActive comparator* 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
Receives: Radiation: Radiotherapy; Drug: Chemotherapy; Procedure: Salvage neck dissection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Defined as time from randomization up to 36 month

Secondary outcomes (8)

  1. Overall survival

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

    Measured: Until 3 years after randomization

  2. 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

    Measured: Until 3 years after randomization

  3. 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

    Measured: Until 3 years after randomization

  4. Effectiveness in terms of morbidity

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

    Measured: Until 3 years after randomization

  5. Quality of life evaluated by patient

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

    Measured: Until 3 years after randomization

  6. Quality of life evaluated by patient

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

    Measured: Until 3 years after randomization

  7. Cost-utility

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

    Measured: Until 3 years after randomization

  8. Cost-effectiveness

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

    Measured: Until 3 years after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Oct 2018
  2. Study start5 Jan 2018
  3. Primary completion5 May 2024 (estimated)
  4. Study completion5 May 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
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)
Enrolment
280 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03691441
Sponsor's protocol ID
TopROC
Status last verified
May 2023
First submitted
2 Mar 2018
Last updated
17 May 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Mehanna H, Beech T, Nicholson T, El-Hariry I, McConkey C, Paleri V, Roberts S. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer--systematic review and meta-analysis of trends by time and region. Head Neck. 2013 May;35(5):747-55. doi: 10.1002/hed.22015. Epub 2012 Jan 20.

    PubMed 22267298

  • Licitra L, Zigon G, Gatta G, Sanchez MJ, Berrino F; EUROCARE Working Group. Human papillomavirus in HNSCC: a European epidemiologic perspective. Hematol Oncol Clin North Am. 2008 Dec;22(6):1143-53, vii-viii. doi: 10.1016/j.hoc.2008.10.002.

    PubMed 19010264

  • Chaturvedi AK, Engels EA, Anderson WF, Gillison ML. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol. 2008 Feb 1;26(4):612-9. doi: 10.1200/JCO.2007.14.1713.

    PubMed 18235120

  • Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C, Kim H, Axelrod R, Silverman CC, Redmond KP, Gillison ML. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010 Jul 1;363(1):24-35. doi: 10.1056/NEJMoa0912217. Epub 2010 Jun 7.

    PubMed 20530316

  • Weinberger PM, Yu Z, Haffty BG, Kowalski D, Harigopal M, Brandsma J, Sasaki C, Joe J, Camp RL, Rimm DL, Psyrri A. Molecular classification identifies a subset of human papillomavirus--associated oropharyngeal cancers with favorable prognosis. J Clin Oncol. 2006 Feb 10;24(5):736-47. doi: 10.1200/JCO.2004.00.3335. Epub 2006 Jan 9.

    PubMed 16401683

  • Pfister DG, Spencer S, Brizel DM, Burtness B, Busse PM, Caudell JJ, Cmelak AJ, Colevas AD, Dunphy F, Eisele DW, Gilbert J, Gillison ML, Haddad RI, Haughey BH, Hicks WL Jr, Hitchcock YJ, Jimeno A, Kies MS, Lydiatt WM, Maghami E, Martins R, McCaffrey T, Mell LK, Mittal BB, Pinto HA, Ridge JA, Rodriguez CP, Samant S, Schuller DE, Shah JP, Weber RS, Wolf GT, Worden F, Yom SS, McMillian NR, Hughes M; National Comprehensive Cancer Network. Head and neck cancers, Version 2.2014. Clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2014 Oct;12(10):1454-87. doi: 10.6004/jnccn.2014.0142.

    PubMed 25313184

  • Gregoire V, Lefebvre JL, Licitra L, Felip E; EHNS-ESMO-ESTRO Guidelines Working Group. Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010 May;21 Suppl 5:v184-6. doi: 10.1093/annonc/mdq185. No abstract available.

    PubMed 20555077

  • Wegscheider K, Drabik A, Bleich C, Schulz H. [Benefit assessment in health services research and epidemiology]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2015 Mar;58(3):298-307. doi: 10.1007/s00103-014-2106-1. German.

    PubMed 25566839

  • Lorincz BB, Mockelmann N, Busch CJ, Knecht R. Functional outcomes, feasibility, and safety of resection of transoral robotic surgery: single-institution series of 35 consecutive cases of transoral robotic surgery for oropharyngeal squamous cell carcinoma. Head Neck. 2015 Nov;37(11):1618-24. doi: 10.1002/hed.23809. Epub 2014 Aug 28.

    PubMed 24955923

  • Boscolo-Rizzo P, Gava A, Baggio V, Marchiori C, Stellin M, Fuson R, Lamon S, Da Mosto MC. Matched survival analysis in patients with locoregionally advanced resectable oropharyngeal carcinoma: platinum-based induction and concurrent chemoradiotherapy versus primary surgical resection. Int J Radiat Oncol Biol Phys. 2011 May 1;80(1):154-60. doi: 10.1016/j.ijrobp.2010.01.032. Epub 2010 Sep 23.

    PubMed 20864267

  • Hicks WL Jr, Kuriakose MA, Loree TR, Orner JB, Schwartz G, Mullins A, Donaldson C, Winston JM, Bakamjian VY. Surgery versus radiation therapy as single-modality treatment of tonsillar fossa carcinoma: the Roswell Park Cancer Institute experience (1971-1991). Laryngoscope. 1998 Jul;108(7):1014-9. doi: 10.1097/00005537-199807000-00012.

    PubMed 9665249

  • O'Hara J, MacKenzie K. Surgical versus non-surgical management of early stage oropharyngeal squamous cell carcinoma. Eur Arch Otorhinolaryngol. 2011 Mar;268(3):437-42. doi: 10.1007/s00405-010-1362-4. Epub 2010 Aug 27.

    PubMed 20799040

  • Worthington HV, Bulsara VM, Glenny AM, Clarkson JE, Conway DI, Macluskey M. Interventions for the treatment of oral cavity and oropharyngeal cancers: surgical treatment. Cochrane Database Syst Rev. 2023 Aug 31;8(8):CD006205. doi: 10.1002/14651858.CD006205.pub5.

    PubMed 37650478

  • Bussmann L, Laban S, Wittekindt C, Stromberger C, Tribius S, Mockelmann N, Bottcher A, Betz CS, Klussmann JP, Budach V, Muenscher A, Busch CJ. Comparative effectiveness trial of transoral head and neck surgery followed by adjuvant radio(chemo)therapy versus primary radiochemotherapy for oropharyngeal cancer (TopROC). BMC Cancer. 2020 Jul 29;20(1):701. doi: 10.1186/s12885-020-07127-2.

    PubMed 32727416

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Resection, Radiotherapy and Chemotherapy in people with Oropharyngeal Cancer, run by Universitätsklinikum Hamburg-Eppendorf at 20 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 17 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to local or locoregional failure or death from any cause (time frame: Defined as time from randomization up to 36 month). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03691441, which also lists 14 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in