Clinical trial NCT00508664: Docetaxel, Cisplatin (TP) + Radiation +/- Cetuximab in Larynx Carcinoma (CA)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of the Hypopharynx
Larynx Carcinoma
Keywords: by laryngectomy operable carcinoma of the larynx and the hypopharynx
Lead sponsor: University of Leipzig
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
name: Sanofi
First posted: 2007-07-30
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Confirmatory proof of an adequate survival rate with a functionally larynx-conserving 2 years after randomisation
timeFrame: LFS-rate 2 years after randomisation
Secondary outcomes:
measure: Descriptive analysis of the study arms concerning the secondary end criteria of the study
timeFrame: LSF 2 years after randomisation
measure: Explorative comparison of the study arms concerning the primary and secondary end criteria of the study
timeFrame: LSF 2 years after randomisation
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Universitätsklinik für HNO
city: Klagenfurt
country: Austria
facility: Landeskrankenhaus Klagenfurt
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus der Stadt Wien
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt GmbH Klinik für HNO-Heilkunde, Plastische Operationen
state: Thüringen
city: Aachen
country: Germany
facility: Universitätsklinik Aachen
city: Berlin
country: Germany
facility: Charité, Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Klinikum Neukölln, Vivantes GmbH
city: Bielefeld
country: Germany
facility: Klinikum Bielefeld-Mitte
city: Duisburg
country: Germany
facility: Malteser Krankenhaus St. Anna gGmbH, HNO-Klinik
city: Fulda
country: Germany
facility: Klinikum Fulda gAG, Klinik für Hals-Nasen-Ohrenkrankheiten
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Hannover
country: Germany
facility: Klinikum Hannover Nordstadt
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Karlsruhe
country: Germany
facility: St. Vincentius Kliniken
city: Kassel
country: Germany
facility: Klinikum Kassel GmbH
city: Koblenz
country: Germany
facility: Katholisches Klinikum Koblenz Marienhof
city: Köln
country: Germany
facility: Universitätsklinik Köln
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Lübeck
country: Germany
facility: Universtitätsklinikum Schleswig-Holstein
city: München
country: Germany
facility: Klinikum Großhadern
city: Münster
country: Germany
facility: Medizinische Fakultät der Westfälischen Wilhelms-Universität Münster
city: Nordhausen
country: Germany
facility: Südharz-Krankenhaus Nordhausen gGmbH
city: Potsdam
country: Germany
facility: Klinikum Ernst von Bergmann gGmbH
city: Regensburg
country: Germany
facility: Universtitätsklinikum Regensburg
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart Katharinenhospital, Klinik für HNO-Krankheiten
city: Würzburg
country: Germany
facility: Bayerischen Julius Maximillians-Universtät Würzburg
Study officials:
affiliation: University of Leipzig
name: Andreas Dietz, Dr. med.
role: STUDY_DIRECTOR
References:
citation: 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.