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

Phase 2

Completed

• Conditions: Squamous Cell Carcinoma of the Hypopharynx Stage IV; Squamous Cell Carcinoma of the Oropharynx Stage III; Squamous Cell Carcinoma of the Larynx Stage III; Squamous Cell Carcinoma of the Oral Cavity Stage IV; Squamous Cell Carcinoma of the Hypopharynx Stage III; Squamous Cell Carcinoma of the Larynx Stage IV; Squamous Cell Carcinoma of the Oropharynx Stage IV; Squamous Cell Carcinoma of the Oral Cavity Stage III
• Interventions: Drug: Docetaxel; Drug: Cisplatin; Biological: Cetuximab Induction; Drug: 5-fluorouracil; Biological: Cetuximab Radioimmunotherapy; Radiation: Boost irradiation

• Registration Number: NCT01884259
• Lead Sponsor: Arbeitsgemeinschaft medikamentoese Tumortherapie

Brief Summary

This multicentre, randomised Phase II Pilot Study evaluates the efficacy of docetaxel, cisplatin and 5-fluorouracil or Cetuximab, followed by Cetuximab with radiotherapy.

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.

Study Timeline

• Study First Submitted: 2012-05-18
• Study Start: 2013-05
• Study First Submitted QC: 2013-06-20
• Study First Posted: 2013-06-24
• Primary Completion: 2021-01-28
• Study Completion: 2022-01-13
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-20
• Last Update Posted: 2022-05-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B	Docetaxel	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.
B	Cetuximab Induction	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.
B	Cetuximab Radioimmunotherapy	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.
A	Cetuximab Radioimmunotherapy	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.
A	Cisplatin	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.
A	Boost irradiation	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.
B	Boost irradiation	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.
A	Docetaxel	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.
A	5-fluorouracil	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.
B	Cisplatin	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.

Primary Outcome Measures

Name	Time	Method
Response Rate (CR, PR)	3 months after end of therapy	RECIST criteria

Secondary Outcome Measures

Name	Time	Method
Overall-Survival	1, 2 and 5 years after start of therapy
Locoregionally monitoring	after one year
Overall Response Rate (CR, PR, PD, SD)	until 3 months after therapy	RECIST
Progression Free Survival (PFS)	1, 2 and 5 years after start of therapy
Adverse reactions	During treatment and until 60 months after end of radiotherapy	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.

Trial Locations

Locations (8)

Hanusch Krankenhaus Wien; 🇦🇹 Vienna, Austria

Universität f. Strahlentherape, AKH Wien; 🇦🇹 Vienna, Austria

Krankenhaus d. Barmherzigen Schwestern Linz; 🇦🇹 Linz, Austria

Landeskrankenhaus Feldkirch; 🇦🇹 Feldkirch, Austria

PMU Salzburg; 🇦🇹 Salzburg, Austria

Kepler Universitätsklinikum, Med Campus III. Klinik für Interne 3 - Schwerpunkt Hämatologie u. Onkologie; 🇦🇹 Linz, Austria

Landesklinikum Krems; 🇦🇹 Krems, Austria

Klinikum Kreuzschwestern Wels GmbH; 🇦🇹 Wels, Austria