TPF Plus Cisplatin and Radiotherapy vs TPF Plus Cetuximab and Radiotherapy to Treat Head and Neck Cancer.

Open Label Randomized, Multi-centre Phase III Trial of TPF Plus Concomitant Treatment With Cisplatin and Radiotherapy Versus Concomitant Cetuximab and Radiotherapy in Locally Advanced, Unresectable Head and Neck Cancer.

An Open Label Randomized, Multi-Centre Phase III Trial of TPF Chemotherapy Plus Concomitant Treatment With Cisplatin and Conventional Radiotherapy Versus TPF Chemotherapy Plus Concomitant Cetuximab and Conventional Radiotherapy in Locally Advanced, Unresectable Head and Neck Cancer.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Other: TPF, radiotherapy and cisplatin.; Other: TPF, radiotherapy and cetuximab.

Detailed Description

This study is being sponsored by a cooperative medical group.

• Study Type: Interventional
• Enrollment (Actual): 519
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Alicante, Spain
    • Hospital General Universitario
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Bilbao, Spain
    • Hospital de Basurto
  • Burgos, Spain
    • Hospital General Yague
  • Cáceres, Spain
    • Hospital San Pedro de Alcantara
  • Girona, Spain, 17007
    • Hospital Dr. Trueta (ICO Girona)
  • Granada, Spain, 18014
    • Oncogranada
  • Granada, Spain
    • H. Virgen de las Nieves
  • Jaén, Spain
    • Hospital General de Jaén
  • Lugo, Spain
    • Hospital Xeral Calde
  • Lérida, Spain, 25198
    • Hospital Universitari Arnau de Vilanova
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Hospital Gregorio Marañón
  • Madrid, Spain
    • Fundacion Jimenez Diaz
  • Madrid, Spain
    • Hospital La Paz
  • Madrid, Spain
    • Clinica Quiron
  • Oviedo, Spain, 33006
    • Hospital Universitario Central de Asturias
  • Salamanca, Spain, 37007
    • Hospital Universitario de Salamanca
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Santiago de Compostela, Spain
    • Hospital Clínico de Santiago
  • Segovia, Spain
    • Hospital General de Segovia
  • Valencia, Spain, 46015
    • Hospital Arnau De Vilanova
  • Valencia, Spain
    • Hospital La Fe
  • Valencia, Spain
    • Hospital General Universitario
  • Vigo, Spain, 36024
    • Hospital Xeral Cíes
  • Vigo, Spain, 36200
    • Hospital de Meixoeiro
  • Zamora, Spain, 49021
    • Hospital Provincial de Zamora
  • Zaragoza, Spain
    • Hospital Miguel Servet
  • Zaragoza, Spain
    • Hospital Clinico Lozano Blesa
  • Ávila, Spain
    • Hospital Nuestra Señora de Sonsoles
  • Almería
    • Almeria, Almería, Spain
      • Hospital Puerta del Mar
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias i Pujol
    • Hospitalet de Ll., Barcelona, Spain
      • Hospital Duran i Reynals
    • Manresa, Barcelona, Spain
      • Hospital de Manresa
    • Terrassa, Barcelona, Spain
      • Hospital Mútua de Terrassa
  • Mallorca
    • Palma De Mallorca, Mallorca, Spain, 07198
      • Hospital Son Llatzer
    • Palma de Mallorca, Mallorca, Spain, 07014
      • Hospital Son Dureta
  • Valencia
    • Sagunto, Valencia, Spain
      • Hospital de Sagunto

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Before the beginning of protocol's specific procedures, the informed consent has to be obtained.
2. Locally advanced cancer of head and neck (oral cavity, oropharynx, larynx and hypopharynx) stage III-IV, without evidence of metastasis.

3. The tumor must be considered to be non-operable according to the criteria of the Northern California Oncology Group. The reason of non-surgical resection will be annotated in the CRF.

   Criteria of non-surgical resection according to the NCOG:

   3.1.Technically not resectable (includes: evidence of mediastinal dissemination; fixed tumor to the clavicle, base of the cranium or cervical vertebrae; affectation of the nasopharynx).

   3.2.Medical criteria based on a low surgical curability. 3.3.Medical contraindication for the surgery.

4. Epidermoid carcinoma histologically demonstrated
5. Measurable disease according to the RECIST criteria .
6. Men or women with age between 18 and 70 years, both inclusive.
7. Functional condition index according to ECOG scale:0-1
8. Patients in medical conditions to be able to receive treatment with TPF induction followed by normofractionated radiotherapy with cetuximab or cisplatin.
9. Patients with adequate hematologic function: neutrophils superior or equal to 2 x 109, platelets superior or equal to 100 x 109, hemoglobin superior or equal to 10 g/dl.
10. Adequate hepatic function: bilirubin lower or equal to 1 x top normal Limit, GOT and GPT lower or equal to 2,5 Top Normal Limit , alkaline phosphatase < 5 Top Normal Limit.
11. Adequate renal function: creatinin <1,4 mg/dl (120 µmol/l); if the values are > 1,4 mg/dl, the clearance of creatinin will have to be > 60 ml/min (real or calculated for Cockcroft-Gault's method).
12. Calcium lower or equal to 1,25 x top normal limit.
13. Adequate nutritional condition: loss of weight <20% with relation to the theoretical weight and albumin superior or equal to 35 g/L.
14. Patients must be accessible for the treatment and the follow-up.

Exclusion Criteria:

1. Metastatic disease
2. Surgical treatment, previous radiotherapy and/or chemotherapy for the study disease.
3. Other tumor locations in head and neck that are not oral cavity, oropharynx, larynx, hypopharynx.
4. Other stages that are not III or IVM0.
5. Other previous and / or synchronic squamous carcinoma.
6. Diagnosis of another neoplasia in the last 5 years, excepting carcinoma in situ of uterine neck and/or a cutaneous carcinoma basocellular properly treated.
7. Active infection(at needs endovenous antibiotics), including active tuberculosis and diagnosed HIV.
8. Not controlled hypertension defined as arterial systolic tension superior or equal to 180 mm Hg and / or diastolic arterial tension superior or equal to 130 mm Hg baseline.
9. Pregnancy(absence must be confirmed with the test of beta-HCG) or period of lactation.
10. Immunity systemic treatment, chronic and concomitant, or hormonal treatment of the cancer.
11. Other antineoplastic concomitant treatments.
12. Coronary clinically significant arteriopathy or precedents of myocardial infarction in the last 12 months or high risk of not controlled arrhythmia or cardiac not controlled insufficiency.
13. Pulmonary obstructive chronic disease that had needed 3 or more hospitalizations in the last 12 months.
14. Active non controlled peptic ulcer.
15. Presence of a psychological or medical disease that could prevent to accomplish the study by the patient or to grant his/her signature in the informed consent form.
16. Known drugs abuse (with the exception of excessive consumption of alcohol)
17. Known allergic reaction to some of the components of the treatment of the study.
18. Previous treatment with monoclonal antibodies or other transduction of the sign inhibitors or treatment directed against the EGFR.
19. Any experimental treatment in 30 days before the entry in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A; TPF plus concomitant treatment with cisplatin and conventional radiotherapy.	Other: TPF, radiotherapy and cisplatin.; 3 cycles of: cisplatin: 75 mg/m2, i.v., 1 hour, once daily docetaxel: 75 mg/m2, i.v., 1 hour, once daily 5-fluorouracil: 750 mg/m2, i.v., 24 hours, 5 days Radiotherapy: 70Gy, divided into daily doses of 2 Gray (total days: 35) Cisplatin: 100 mg/m2, i.v., 1 hour, 3 days; Other Names: TPF plus radiotherapy and cisplatin
Experimental: Group B; TPF plus concomitant treatment with cetuximab and conventional radiotherapy	Other: TPF, radiotherapy and cetuximab.; 3 cycles of: cisplatin: 75 mg/m2, i.v., 1 hour, once daily docetaxel: 75 mg/m2, i.v., 1 hour, once daily 5-fluorouracil: 750 mg/m2, i.v., 24 hours, 5 days Radiotherapy: 70Gy, divided into daily doses of 2 Gray (total days: 35) Cetuximab: 400 mg/m2, i.v, 2 hours, 1 day Cetuximab: 250 mg/m2, i.v, 1 hour, 7 days; Other Names: TPF plus radiotherapy and cetuximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global survival	The time from the start of induction chemotherapy with TPF to death due to any cause or to the last check-up in the case of living patients	Up to 89 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	The response rate (CR + PR) measured using the RECIST 1.0 method.	Up to 89 months
Progression free-survival (PFS)	Time to progression as the time since the start date of treatment with TPF induction chemotherapy until the time when DP occurred or death occurred due to any cause.	Up to 89 months
Time to loco-regional control of disease	As permanent and complete resolution of the disease in terms of its initial site and lymph nodes (T and N). If the disease lasted (regardless of size), the tumor recurred, or a second tumor appeared in the field RT, it will be recorded as a therapeutic failure.	Up to 89 months
Satisfaction with treatment. Analysis of QoL in both treatment arms.	EORTC QoL questionnaires: C30 version 3.0 and QLQ-H&N35 module	Up to 89 months

Collaborators and Investigators

• Sponsor: Grupo Español de Tratamiento de Tumores de Cabeza y Cuello
• Investigators: Principal Investigator: Juan J Cruz, Professor, University of Salamanca; Principal Investigator: Ricardo Hitt, MD, Hospital Universitario 12 de Octubre

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2008
• Primary Completion (Actual): July 18, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: July 14, 2008
• First Submitted That Met QC Criteria: July 14, 2008
• First Posted (Estimate): July 16, 2008

Study Record Updates

• Last Update Posted (Actual): May 24, 2019
• Last Update Submitted That Met QC Criteria: May 21, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Head and Neck Cancer
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cisplatin; Cetuximab
• Other Study ID Numbers: TTCC-2007-01