Docetaxel, Cisplatin (TP) + Radiation +/- Cetuximab in Larynx Carcinoma (CA) (DeLOS II)

Randomised Phase II Screening Study to be Used in an TP/TPF-chemotherapy (Short Induction) Before TP/TPF-induction, Radiotherapy With or Without Cetuximab in the Primary Therapy of the Only by Laryngectomy Operable Carcinoma of the Larynx/Hypopharynx

The DeLOS II trial is a multicenter randomised phase II trial investigating a TP/5-Fluorouracil (TPF)-chemotherapy with or without cetuximab for Patients with only by laryngectomy operable carcinoma of the larynx/hypopharynx. Patients were divided in responder or non-responder after 4 weeks. Since August 2009 Responder receive TP with or without Cetuximab + radiation. (Until february 2009 Responder received TPF with or without Cetuximab + radiation.) Planned accrual is 85 patients per treatment arm. The primary study endpoint is a confirmatory proof of an adequate survival rate with a functionally larynx-conserving 2 years after randomisation.

Study Overview

• Status: Completed
• Conditions: Squamous Cell Carcinoma of the Hypopharynx; Larynx Carcinoma
• Intervention / Treatment: Radiation: Radiation; Drug: Docetaxel; Drug: Cisplatin (TP); Drug: 5-Fluorouracil (TPF) (only until Feb 2009); Drug: Cetuximab

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • Universitätsklinik für HNO
  • Klagenfurt, Austria, A-9020
    • Landeskrankenhaus Klagenfurt
  • Vienna, Austria, 1090
    • Allgemeines Krankenhaus der Stadt Wien
• Germany
  • Aachen, Germany, 52074
    • Universitätsklinik Aachen
  • Berlin, Germany, 12200
    • Charite, Campus Benjamin Franklin
  • Berlin, Germany, 12351
    • Klinikum Neukölln, Vivantes GmbH
  • Bielefeld, Germany, 33604
    • Klinikum Bielefeld-Mitte
  • Duisburg, Germany, 47259
    • Malteser Krankenhaus St. Anna gGmbH, HNO-Klinik
  • Fulda, Germany, 36043
    • Klinikum Fulda gAG, Klinik für Hals-Nasen-Ohrenkrankheiten
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Hannover, Germany
    • Klinikum Hannover Nordstadt
  • Heidelberg, Germany, 69120
    • Universitatsklinikum Heidelberg
  • Jena, Germany, 07743
    • Universitatsklinikum Jena
  • Karlsruhe, Germany
    • St. Vincentius Kliniken
  • Kassel, Germany, 34125
    • Klinikum Kassel Gmbh
  • Koblenz, Germany, 56073
    • Katholisches Klinikum Koblenz Marienhof
  • Köln, Germany, 50924
    • Universitätsklinik Köln
  • Leipzig, Germany, 04103
    • Universitatsklinikum Leipzig
  • Lübeck, Germany, 23538
    • Universtitätsklinikum Schleswig-Holstein
  • München, Germany, 81377
    • Klinikum Großhadern
  • Münster, Germany, 48149
    • Medizinische Fakultät der Westfälischen Wilhelms-Universität Münster
  • Nordhausen, Germany
    • Südharz-Krankenhaus Nordhausen gGmbH
  • Potsdam, Germany, 14467
    • Klinikum Ernst von Bergmann gGmbH
  • Regensburg, Germany
    • Universtitätsklinikum Regensburg
  • Stuttgart, Germany, 70174
    • Klinikum Stuttgart Katharinenhospital, Klinik für HNO-Krankheiten
  • Würzburg, Germany, 97080
    • Bayerischen Julius Maximillians-Universtät Würzburg
  • Thüringen
    • Erfurt, Thüringen, Germany, 99089
      • Helios Klinikum Erfurt GmbH Klinik für HNO-Heilkunde, Plastische Operationen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed, primary only with laryngectomy respectable squamous-cell carcinoma of the larynx or hypopharynx
• T3-T4a carcinoma of the glottis
• T2-T4a carcinoma of the supraglottic, only controllable by laryngectomy and if applicable by root of tongue segmental resection
• T2-T4a carcinoma of the hypopharynx only controllable by laryngectomy (for example T2, post cricoidal) and hypopharynx segmental resection

• N-status: cervical metastases (N0-N3) have to be rehabilitate by surgical procedures

  • Blood count: Leukocytes >3500/mm\3, Neutrophils > 1500/ mm\3, Thrombocytes > 8000/ mm\3
  • Clinical chemistry:
• adequate renal function, defined by serum creatinine and urea not higher than 25% upper NL, creatinine-clearance > 60 ml/min/1,72 m\2
• adequate hepatic function with SGOT, SGPT not higher than 50% and bilirubin not higher than upper NL

• electrolytes at NL

  • anesthetic risk normal or low-grade elevated
  • age 18-75 years
  • written informed consent
  • effective contraception after individual advice for men and women if there is a possibility of reproductive potential (effective contraception are: oral contraception with estrogen and gestagen (no minipill), vaginal ring, contraception patch, estrogen free ovulation suppressors, hormone spiral with progesterone, injection for three month with depot gestagen, hormone releasing implantation (luteal hormone containing rod), abstinence or sterilization (vasectomy) of the male)

Exclusion Criteria:

• primary cancer treatable by operational larynx -conserving procedures
• distant metastases (M1-Status)
• total tumor volume exceeding 80 ml or larynx skeleton punctuated with infiltration of surrounding soft tissues respectively the esophageal aditus (exclusive cartilage infiltration represents no exclusion criteria)
• tumor-specific prior chemo or radiotherapy
• metachronous or synchronous malignant tumor (exception basalioma) [in case of a controlled tumor of different localization with a non-treated interval over 5 years to the present therapy the patient can be included after consultation with the coordinating investigator]
• life expectancy < 3 month
• Karnofsky performance status < 70%
• serious cardiopulmonary concomitant disease (cardiac insufficiency grade III and IV according NYHA status, myocardial infarction, angina pectoris, respiratory global insufficiency)
• Chronic diseases with permanent-therapy (uncontrolled diabetes, active rheumatoid arthritis)
• recurrent pneumonia, COPD GOLD stage <2, chronic inflammation of intestine or any other concomitant diseases, which disallow study participation in the opinion of the responsible physician
• Other circumstances (contra-indications), which disallow treatment with Docetaxel, Cisplatin, 5-FU, Cetuximab or radiotherapy
• Expected absent patient compliance
• Periodic follow-up not possible (for example address outside germany)
• Pregnant or breast-feeding woman
• Absent or constricted legal capacity
• Participation to another clinical trial with any investigational study within 30 days prior to study screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A; TP + Radiation (TPF until Feb 2009)	Radiation: Radiation; Radiation start in week 11; Drug: Docetaxel; 75 mg/m2 i.v. day 1 3 times; Other Names: Taxotere; Drug: Cisplatin (TP); 75 mg/m2 i.v. day 1 3 times; Drug: 5-Fluorouracil (TPF) (only until Feb 2009); Only patients recruited until Feb 2009: 750 mg/m2 i.v. day 1-5, 3 times
EXPERIMENTAL: B; TP + Cetuximab + Radiation (TPF until Feb 2009)	Radiation: Radiation; Radiation start in week 11; Drug: Docetaxel; 75 mg/m2 i.v. day 1 3 times; Other Names: Taxotere; Drug: Cisplatin (TP); 75 mg/m2 i.v. day 1 3 times; Drug: 5-Fluorouracil (TPF) (only until Feb 2009); Only patients recruited until Feb 2009: 750 mg/m2 i.v. day 1-5, 3 times; Drug: Cetuximab; Day 1 400mg/m2 i.v. than weekly 250 mg/m2 i.v. for 16 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Confirmatory proof of an adequate survival rate with a functionally larynx-conserving 2 years after randomisation	LFS-rate 2 years after randomisation

Secondary Outcome Measures

Outcome Measure	Time Frame
Descriptive analysis of the study arms concerning the secondary end criteria of the study	LSF 2 years after randomisation
Explorative comparison of the study arms concerning the primary and secondary end criteria of the study	LSF 2 years after randomisation

Collaborators and Investigators

• Sponsor: ClinAssess
• Collaborators: Sanofi; Merck Sharp & Dohme LLC
• Investigators: Study Director: Andreas Dietz, Dr. med., University of Leipzig

Publications and helpful links

General Publications

• Dietz A, Wichmann G, Kuhnt T, Pfreundner L, Hagen R, Scheich M, Kolbl O, Hautmann MG, Strutz J, Schreiber F, Bockmuhl U, Schilling V, Feyer P, de Wit M, Maschmeyer G, Jungehulsing M, Schroeder U, Wollenberg B, Sittel C, Munter M, Lenarz T, Klussmann JP, Guntinas-Lichius O, Rudack C, Eich HT, Foerg T, Preyer S, Westhofen M, Welkoborsky HJ, Esser D, Thurnher D, Remmert S, Sudhoff H, Gorner M, Bunzel J, Budach V, Held S, Knodler M, Lordick F, Wiegand S, Vogel K, Boehm A, Flentje M, Keilholz U. Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II. Ann Oncol. 2018 Oct 1;29(10):2105-2114. doi: 10.1093/annonc/mdy332.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (ACTUAL): February 1, 2015
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: July 27, 2007
• First Submitted That Met QC Criteria: July 27, 2007
• First Posted (ESTIMATE): July 30, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): June 2, 2015
• Last Update Submitted That Met QC Criteria: June 1, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: by laryngectomy operable carcinoma of the larynx and the hypopharynx
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Otorhinolaryngologic Diseases; Carcinoma; Laryngeal Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Cisplatin; Fluorouracil; Cetuximab
• Other Study ID Numbers: TP(F)+Radiation+/-Cetuximab