TPF Plus Radiotherapy and Cetuximab to Avoid Total Laryngectomy in Patients With Larynx Cancer

A Phase II Trial With Radiotherapy Plus Cetuximab to Evaluate Specific Survival Free of Laryngectomy in Patients With Resectable and Locally Advanced Larynx Cancer, After Treatment With TPF

A Phase II Trial With Radiotherapy Plus Cetuximab to Evaluate Specific Survival Free of Laryngectomy in Patients With Resectable and Locally Advanced Larynx Cancer, After Treatment With TPF Chemotherapy.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: TPF, radiotherapy and cetuximab; Procedure: H&N surgery

Detailed Description

This study is being sponsored by a cooperative medical group.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Cáceres, Spain
    • Hospital San Pedro de Alcántara
  • Girona, Spain, 17007
    • Hospital Dr.Josep Trueta (ICO Girona)
  • Granada, Spain
    • Hospital Universitario Virgen de las Nieves
  • Granada, Spain
    • Oncogranada
  • Lugo, Spain
    • Hospital Xeral Calde
  • Madrid, Spain
    • Hospital Gregorio Marañón
  • Madrid, Spain
    • Hospital Universitario 12 de octubre
  • Madrid, Spain
    • Hospital Universitario San Carlos
  • Palma De Mallorca, Spain
    • Hospital Son Llatzer
  • Salamanca, Spain
    • Hospital Universitario de Salamanca
  • Valencia, Spain
    • Hospital Universitario La Fe de Valencia
  • Zaragoza, Spain
    • Hospital Miguel Servet
  • Zaragoza, Spain
    • Hospital Clínico Universitario de Zaragoza
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias i Pujol
    • L'Hospitalet de Llobregat, Barcelona, Spain
      • Hospital Duran I Reynals
    • Manresa, Barcelona, Spain
      • Hospital de Manresa

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. Signed Informed Consent Form.
2. Men or women, age (18 and 70).
3. ECOG scale:0-1.
4. Life expectancy superior to 3 months.
5. Larynx squamous carcinoma histologically demonstrated.
6. Patients with larynx squamous carcinoma, stage III-IVA, with resectable disease whose surgery will imply a total laryngectomy. The T should be a T3, T4A, or a T2 not candidate for a partial laryngectomy. In case of T2 of any of both locations it will be required a III or IVA stadium.
7. Patients to be able to receive treatment with TPF followed by normofractionated radiotherapy with cetuximab.
8. Measurable disease (OMS criteria).
9. Neutrophils superior or equal to 1500/mm3, platelets superior or equal to 150.000/mm3, hemoglobin superior or equal to 10 g/dl.
10. Adequate renal function: creatinin lower or equal to 120 µmol/l (1,4mg/dl)
11. Adequate hepatic function: bilirubin lower or equal to 1 x UNL, AST and ALT lower or equal to 2,5 UNL, alkaline phosphatase lower or equal to 5 UNL.
12. Seric calcium adjusted to albumine lower or equal to 1,25 UNL.
13. Adequate nutritional condition: loss of weight <20% with relation to the theoretical weight and albumin superior or equal to 35 g/L.
14. Use of an effective contraceptive method.

Exclusion Criteria:

1. Metastatic disease
2. Surgical treatment, previous radiotherapy and/or chemotherapy for the study disease.
3. Other tumour locations in H&N that are not larynx.
4. Other stages that are not III or IVa without metastasis and resectable disease.

5. The following cases, which will be considered candidates for radical surgery, will not be included in the study:

   • Tumors of the subglottis.
   • Tumors of glottis or supraglottis with subglottal extension
   • Tumor that destroys the thyroid cartilage and/or cricoid and it extends to thyroid gland or soft necks's tissues.
   • Tumor of supraglottis with a superior extension to 1 cm towards the tongue base (the extension will be measured since the vallecula).
6. Other previous and/or synchronic squamous carcinoma.
7. Diagnosis of another neoplasia in the last 5 years, excepting carcinoma in situ of uterine neck and/or a cutaneous carcinoma basocellular properly treated.
8. Active infection(at needs endovenous antibiotics), including active tuberculosis and diagnosed HIV.
9. 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.
10. Pregnancy or breastfeeding.
11. Immunity systemic treatment, chronic and concomitant, or hormonal treatment of the cancer.
12. Other antineoplasic concomitant treatments.
13. 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.
14. Pulmonary obstructive chronic disease that had needed 3 or more hospitalizations in the last 12 months.
15. Active non controlled peptic ulcer.
16. 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.
17. Known drugs abuse (excepting excessive consumption of alcohol).
18. Known allergic reaction to some of the components of the treatment of the study.
19. Previous treatment with monoclonal antibodies or other transduction of the sign inhibitors or treatment directed against the EGFR.
20. Any experimental treatment in 30 days before entry in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A; TPF plus concomitant treatment with cetuximab and conventional radiotherapy	Drug: TPF, radiotherapy and cetuximab; 3 cycles of: cisplatin: 75mg/m2, i.v., 1 hour, once daily docetaxel: 75 mg/m2, i.v., 1 hour, once daily 5-fluorouracilo: 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
OTHER: Grupo B; Surgery	Procedure: H&N surgery; Rescue surgery; Other Names: Rescue surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Specific survival free of total laryngectomy	Time from the start of TPF treatment to death caused by the disease or by the treatment of the disease, or even to surgery involving total laryngectomy. Deaths caused by other reasons were considered "censored" data on the date of death.	Three years after the end of treatment with radiotherapy and cetuximab

Collaborators and Investigators

• Sponsor: Grupo Español de Tratamiento de Tumores de Cabeza y Cuello
• Investigators: Principal Investigator: Ricard Mesía Nin, MD, Hospital Duran I Reynals; Principal Investigator: José A. García Sáenz, MD, Hospital San Carlos, Madrid

Publications and helpful links

Helpful Links

• This site would like to expose the activities of the group and at the same time serve as an information and communication tool of this pathology for professionals and patients.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (ACTUAL): February 1, 2014
• Study Completion (ACTUAL): May 12, 2015

Study Registration Dates

• First Submitted: October 1, 2008
• First Submitted That Met QC Criteria: October 1, 2008
• First Posted (ESTIMATE): October 2, 2008

Study Record Updates

• Last Update Posted (ACTUAL): April 11, 2019
• Last Update Submitted That Met QC Criteria: April 9, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Head and Neck Cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Neoplasms by Site; Respiratory Tract Neoplasms; Otorhinolaryngologic Neoplasms; Otorhinolaryngologic Diseases; Laryngeal Diseases; Head and Neck Neoplasms; Laryngeal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: TTCC-2007-02