Induction Chemotherapy With TP+5-FU or TP+Cetuximab Followed by Radioimmuptherapy for Locally Advanced or Not Resectable SCCHNN (HNO-2)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Arbeitsgemeinschaft medikamentoese Tumortherapie
ClinicalTrials.gov Identifier:
NCT01884259
First received: May 18, 2012
Last updated: June 1, 2016
Last verified: June 2016
  Purpose
This multicentre, randomised Phase II Pilot Study evaluates the efficacy of docetaxel, cisplatin and 5-fluorouracil or Cetuximab, followed by Cetuximab with radiotherapy.

Condition Intervention Phase
Squamous Cell Carcinoma of the Hypopharynx Stage III
Squamous Cell Carcinoma of the Hypopharynx Stage IV
Squamous Cell Carcinoma of the Larynx Stage III
Squamous Cell Carcinoma of the Larynx Stage IV
Squamous Cell Carcinoma of the Oropharynx Stage III
Squamous Cell Carcinoma of the Oropharynx Stage IV
Squamous Cell Carcinoma of the Oral Cavity Stage III
Squamous Cell Carcinoma of the Oral Cavity Stage IV
Drug: Docetaxel
Drug: Cisplatin
Drug: 5-fluorouracil
Biological: Cetuximab Induction
Biological: Cetuximab Radioimmunotherapy
Radiation: Boost irradiation
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomised Phase II Pilot Study: Induction Chemotherapy With Docetaxel, Cisplatin and Cetuximab Versus Docetaxel, Cisplatin and 5 FU Followed by Radiotherapy With Cetuximab for Locally Advanced or Not Resectable Carcinoma of the Head and Neck

Resource links provided by NLM:


Further study details as provided by Arbeitsgemeinschaft medikamentoese Tumortherapie:

Primary Outcome Measures:
  • Response Rate (CR, PR) [ Time Frame: 3 months after end of therapy ] [ Designated as safety issue: No ]
    RECIST criteria


Secondary Outcome Measures:
  • Overall Response Rate (CR, PR, PD, SD) [ Time Frame: until 3 months after therapy ] [ Designated as safety issue: No ]
    RECIST

  • Locoregionally monitoring [ Time Frame: after one year ] [ Designated as safety issue: No ]
  • Progression Free Survival (PFS) [ Time Frame: 1, 2 and 5 years after start of therapy ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: During treatment and until 60 months after end of radiotherapy ] [ Designated as safety issue: Yes ]

    Information about acute toxicity (grade, relation to study drug) during study treatment and until 3 months after end of radiotherapy will be collected for each patient using CTCAE 3.0 criteria list.

    Information about late toxicity (grade) will be collected after 3 months of radiotherapy and until 60 months after radiotherapy using RTOG/EORTC toxicity criteria.

    Kind and number of toxicities will be described according to grade. The highest grade of each patient and toxicity will be analysed.


  • Overall-Survival [ Time Frame: 1, 2 and 5 years after start of therapy ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: May 2013
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A

Patients receive 3 cycles (cycle duration 21 days) of docetaxel (75mg/m²), cisplatin (75mg/m²) and 5-fluorouracil (750mg/m²) followed by Cetuximab (weekly, starting with 400mg/m² then continuing with 250 mg/m²) with radiotherapy (concomitant boost for 6 weeks).

Active comparator is 5-fluorouracil for first three cycles.

Drug: Docetaxel
75 mg/m² on day 1 of 21-days cycle
Drug: Cisplatin
75 mg/m² on day 1 of 21-days cycle
Drug: 5-fluorouracil
750 mg/m² day 1 to 5 during 24 hours of 21-days cycle
Biological: Cetuximab Radioimmunotherapy
weekly, starting with 400 mg/m² during 120 min.(saturation only arm A) then continuing with 250 mg/m²; duration 7 weeks
Other Name: Erbitux
Radiation: Boost irradiation
First 18 irradiations once daily with single dose of 1,8 Gy for 5 days per week. In addition by day 19 a second irradiation boost will be applied for further 12 days(1,5 Gy per day with at least 5 hours interval to 1,8 Gy dose. This results in total clinical target dose of 72 Gy and total subclinical target dose of 54 Gy. Duration of irradiation: 6 weeks
Other Name: Concomitant boost-irradiation
Experimental: B

All patients receive 3 cycles (cycle duration 21 days) of docetaxel (75mg/m²), cisplatin (75mg/m²) Cetuximab (weekly, starting with 400mg/m² and continuing with 250 mg/m²), followed by Cetuximab (weekly 250 mg/m²) with radiotherapy (concomitant boost for 6 weeks).

Experimental: cetuximab for the first three cycles.

Drug: Docetaxel
75 mg/m² on day 1 of 21-days cycle
Drug: Cisplatin
75 mg/m² on day 1 of 21-days cycle
Biological: Cetuximab Induction
weekly, starting with 400 mg/m² during 120 min.(saturation) then continuing with 250 mg/m²; duration 3 cycles with 21 days
Other Name: Erbitux
Biological: Cetuximab Radioimmunotherapy
weekly, starting with 400 mg/m² during 120 min.(saturation only arm A) then continuing with 250 mg/m²; duration 7 weeks
Other Name: Erbitux
Radiation: Boost irradiation
First 18 irradiations once daily with single dose of 1,8 Gy for 5 days per week. In addition by day 19 a second irradiation boost will be applied for further 12 days(1,5 Gy per day with at least 5 hours interval to 1,8 Gy dose. This results in total clinical target dose of 72 Gy and total subclinical target dose of 54 Gy. Duration of irradiation: 6 weeks
Other Name: Concomitant boost-irradiation

Detailed Description:
It will be evaluated whether 5-FU can be replaced by immunotherapy with cetuximab within a taxane/cisplatin-containing induction-chemotherapy scheme for advanced carcinoma of the head and neck. As 5-FU causes severe mucosal toxicities which are added to known toxicities of cisplatin, a combination-therapy with reduced toxicities and same efficacy would be a acceptable alternative to patients.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed local advanced squamous cell carcinoma of the Larynx, Hypopharynx, Oropharynx or Cavum oris stage III and IV
  • One measureable lesion (CT oder MR)
  • Age 18 - 75 (including)
  • Performance Score ECOG 0 - 1

Exclusion Criteria selected:

  • Distant metastases
  • ECOG Score >1
  • Prior radiation (Head and neck area)
  • Creatinin Clearance below 60 ml/µl
  • Acute infections
  • Neuropathy grade 3 or 4
  • Myocardial Infarction within the last 12 months
  • Acute coronary syndrome or othe clinically significant cardiovascular diseases
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01884259

Locations
Austria
Landeskrankenhaus Feldkirch
Feldkirch, Austria, A-6807
Landesklinikum Krems
Krems, Austria, A-3500
Krankenhaus d. Barmherzigen Schwestern Linz
Linz, Austria, A-4010
Kepler Universitätsklinikum, Med Campus III. Klinik für Interne 3 - Schwerpunkt Hämatologie u. Onkologie
Linz, Austria, A-4021
PMU Salzburg
Salzburg, Austria, 5020
Hanusch Krankenhaus Wien
Vienna, Austria, 1140
Universität f. Strahlentherape, AKH Wien
Vienna, Austria, A-1090
Klinikum Kreuzschwestern Wels GmbH
Wels, Austria, A-4600
Sponsors and Collaborators
Arbeitsgemeinschaft medikamentoese Tumortherapie
Investigators
Principal Investigator: Felix Keil, Prof.Dr. Hanuschkrankenhaus
  More Information

Additional Information:
Responsible Party: Arbeitsgemeinschaft medikamentoese Tumortherapie
ClinicalTrials.gov Identifier: NCT01884259     History of Changes
Other Study ID Numbers: AGMT_HNO 2 
Study First Received: May 18, 2012
Last Updated: June 1, 2016
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Arbeitsgemeinschaft medikamentoese Tumortherapie:
local advanced squamous cell carcinoma
Larynx
Hypopharynx
Oropharynx
Cavum oris
docetaxel
cisplatin
5-fluorouracil
Cetuximab

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Laryngeal Diseases
Laryngeal Neoplasms
Oropharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Respiratory Tract Neoplasms
Pharyngeal Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Docetaxel
Cisplatin
Cetuximab
Fluorouracil
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents

ClinicalTrials.gov processed this record on August 29, 2016