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

NCT03691441 | Unknown Phase 4 DMC

• 1 other identifier: TopROC
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 20

Brief Summary

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

Conditions

Oropharyngeal Cancer

Keywords

locally advanced; transorally resectable

Outcome Measures

Primary Outcomes (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).

  Defined as time from randomization up to 36 month

Secondary Outcomes (8)

• Overall survival

  Until 3 years after randomization

• Disease-free survival

  Until 3 years after randomization

• Effectiveness in terms of toxicity

  Until 3 years after randomization

• Effectiveness in terms of morbidity

  Until 3 years after randomization

• Quality of life evaluated by patient

  Until 3 years after randomization

Other Outcomes (1)

• Tertiary objectives include comparisons of treatment effects between HPV- Status

  Up to 36 month

Study Arms (2)

Resection/adjuvant radio(-chemo)therapy

EXPERIMENTAL

* 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; Radiation: Radiotherapy; Drug: Chemotherapy

Adjuvant radio(-chemo)therapy/salvage neck dissection

ACTIVE 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

Radiation: Radiotherapy; Drug: Chemotherapy; Procedure: Salvage neck dissection

Interventions

Resection PROCEDURE

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.

Also known as: Transoral Surgery

Resection/adjuvant radio(-chemo)therapy

Radiotherapy RADIATION

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

Adjuvant radio(-chemo)therapy/salvage neck dissection; Resection/adjuvant radio(-chemo)therapy

Chemotherapy DRUG

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.

Adjuvant radio(-chemo)therapy/salvage neck dissection; Resection/adjuvant radio(-chemo)therapy

Salvage neck dissection PROCEDURE

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

Adjuvant radio(-chemo)therapy/salvage neck dissection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (20)

Universitäts- HNO- Klinik Mannhein

Mannheim, Baden- Würtemberg, 68167, Germany

Location

St. Vincentius- Kliniken Karlsruhe

Karlsruhe, Baden-Wurttemberg, 76135, Germany

Location

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, 89075, Germany

Location

Helios Amper- Klinikum Dachau

Dachau, Bavaria, 85221, Germany

Location

Ruppiner Klinken GmbH

Neuruppin, Brandenburg, 16816, Germany

Location

Klinikum Ernst von Bergmann gemeinnützige GmbH

Potsdam, Brandenburg, 14467, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

Location

Universitätsklinikum Gießen

Giessen, Hesse, 35385, Germany

Location

Philipps-Universität Marburg

Marburg, Hesse, 35037, Germany

Location

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

Stade, Lower Saxony, 21682, Germany

Location

Klinikum Wolfsburg

Wolfsburg, Lower Saxony, 38440, Germany

Location

Universitätsklinikum Köln

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Kreiskliniken Gummersbach-Waldbröl GmbH Klinik Oberberg

Gummersbach, North Rhine-Westphalia, 51643, Germany

Location

Katholischen Krankenhaus Koblenz

Koblenz, Rhineland-Palatinate, 56073, Germany

Location

Universität des Saarlandes

Homburg, Saarland, 22421, Germany

Location

Universitätsklinik Leipzig / Borna Sana Kliniken Leipziger Land

Leipzig, Saxony, 04103, Germany

Location

Universitätsklinikum Schleswig-Holstein Campus Lübeck

Lübeck, Schleswig-Holstein, 23538, Germany

Location

Universitätsklinikum Jena

Jena, Thuringia, 07757, Germany

Location

Berlin Charité

Berlin, 13353, Germany

Location

Universitätsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Related Publications (14)

• 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.

  PMID: 22267298 BACKGROUND

• 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.

  PMID: 19010264 BACKGROUND

• 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.

  PMID: 18235120 BACKGROUND

• 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.

  PMID: 20530316 BACKGROUND

• 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.

  PMID: 16401683 BACKGROUND

• 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.

  PMID: 25313184 BACKGROUND

• 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.

  PMID: 20555077 BACKGROUND

• 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.

  PMID: 25566839 BACKGROUND

• 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.

  PMID: 24955923 BACKGROUND

• 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.

  PMID: 20864267 BACKGROUND

• 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.

  PMID: 9665249 BACKGROUND

• 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.

  PMID: 20799040 BACKGROUND

• 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.

  PMID: 37650478 DERIVED

• 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.

  PMID: 32727416 DERIVED

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

Radiotherapy; Drug Therapy

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Chia-Jung Busch, PD Dr.

  Universitätsklinikum Hamburg-Eppendorf

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 2, 2018
• First Posted: October 1, 2018
• Study Start: January 5, 2018
• Primary Completion: May 5, 2024
• Study Completion: May 5, 2024
• Last Updated: May 17, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (20)