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

Squamous Cell Carcinoma of the Hypopharynx Clinical Trial

— DeLOS II  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00508664
• Other study ID #: TP(F)+Radiation+/-Cetuximab
• Status: Completed
• Phase: Phase 2
• First received: July 27, 2007
• Last updated: June 1, 2015
• Start date: July 2007
• Est. completion date: February 2015

Study information

• Verified date: June 2015
• Source: University of Leipzig
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-Institut
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Laryngeal Diseases
• Laryngeal Neoplasms
• Larynx Carcinoma
• Squamous Cell Carcinoma of the Hypopharynx

Intervention

Radiation:
• Radiation
Radiation start in week 11

Drug:
• Cetuximab
Day 1 400mg/m2 i.v. than weekly 250 mg/m2 i.v. for 16 weeks
• Docetaxel
75 mg/m2 i.v. day 1 3 times
• Cisplatin (TP)
75 mg/m2 i.v. day 1 3 times
• 5-Fluorouracil (TPF) (only until Feb 2009)
Only patients recruited until Feb 2009: 750 mg/m2 i.v. day 1-5, 3 times

Locations

Country	Name	City	State
Austria	Universitätsklinik für HNO	Graz
Austria	Landeskrankenhaus Klagenfurt	Klagenfurt
Austria	Allgemeines Krankenhaus der Stadt Wien	Vienna
Germany	Universitätsklinik Aachen	Aachen
Germany	Charité, Campus Benjamin Franklin	Berlin
Germany	Klinikum Neukölln, Vivantes GmbH	Berlin
Germany	Klinikum Bielefeld-Mitte	Bielefeld
Germany	Malteser Krankenhaus St. Anna gGmbH, HNO-Klinik	Duisburg
Germany	Helios Klinikum Erfurt GmbH Klinik für HNO-Heilkunde, Plastische Operationen	Erfurt	Thüringen
Germany	Klinikum Fulda gAG, Klinik für Hals-Nasen-Ohrenkrankheiten	Fulda
Germany	Klinikum Hannover Nordstadt	Hannover
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Jena	Jena
Germany	St. Vincentius Kliniken	Karlsruhe
Germany	Klinikum Kassel GmbH	Kassel
Germany	Katholisches Klinikum Koblenz Marienhof	Koblenz
Germany	Universitätsklinik Köln	Köln
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Universtitätsklinikum Schleswig-Holstein	Lübeck
Germany	Klinikum Großhadern	München
Germany	Medizinische Fakultät der Westfälischen Wilhelms-Universität Münster	Münster
Germany	Südharz-Krankenhaus Nordhausen gGmbH	Nordhausen
Germany	Klinikum Ernst von Bergmann gGmbH	Potsdam
Germany	Universtitätsklinikum Regensburg	Regensburg
Germany	Klinikum Stuttgart Katharinenhospital, Klinik für HNO-Krankheiten	Stuttgart
Germany	Bayerischen Julius Maximillians-Universtät Würzburg	Würzburg

Sponsors (3)

Lead Sponsor	Collaborator
ClinAssess	Merck Sharp & Dohme Corp., Sanofi

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmatory proof of an adequate survival rate with a functionally larynx-conserving 2 years after randomisation		LFS-rate 2 years after randomisation	Yes
Secondary	Descriptive analysis of the study arms concerning the secondary end criteria of the study		LSF 2 years after randomisation	No
Secondary	Explorative comparison of the study arms concerning the primary and secondary end criteria of the study		LSF 2 years after randomisation	No