Platinum-Cetuximab Combined With Docetaxel or With 5FU in Patients With Recurrent/Metastatic HNSCC

NCT02268695 | Completed Phase 2 DMC

• 1 other identifier: GORTEC 2014-01
• Study Type: interventional
• Target: 541
• Locations: 3 countries
• Sites: 17

Brief Summary

This study evaluates the efficacy of the new docetaxel-cisplatin-cetuximab regimen (TPEx) versus the standard platinum-5FU-cetuximab EXTREME regimen as a first-line treatment in recurrent and/or metastatic HNSCC. Half of patients will be treated by TPEx regimen, while the other half will be treated by EXTREME regimen.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

Recurrent/Metastatic HNSCC; Taxanes

Outcome Measures

Primary Outcomes (1)

• Overall survival

  Overall survival is defined as the time to death from any cause measured from randomization. Patients with disease progression may be treated with off protocol therapy but will be followed for overall survival evaluation.

  Until patient death or at least one year after the end of the treatment

Secondary Outcomes (9)

• Objective response rate

  At 12 weeks

• Best overall tumor response rate

  until progression or at least one year after the end of the treatment

• Progression free survival

  until progression or death or at least one year after the end of the treatment

• Time to Progression

  until progression or death or at least one year after the end of the treatment

• Toxicity

  until the end of the maintenance, an expected average of 4 months of maintenance

Study Arms (2)

EXTREME: Cisplatin, 5-FU and Cetuximab

ACTIVE COMPARATOR

Chemotherapy: 6 cycles (every 3 weeks) of Cisplatin (100 mg/m² iv on Day1), 5FU (4000 mg/m² total dose starting on day 1 and during 96h in continuous infusion), and Cetuximab (loading dose of 400 mg/m² iv on Day1, then 250 mg/m² iv weekly). If cisplatin is not tolerated and/or when the total cumulative dose of cisplatin (including prior administration) reaches 600 mg/m², cisplatin has to be replaced by carboplatin, AUC 5 (but not exceeding 750 mg), except in the case of bleeding tumor. Cetuximab maintenance : cetuximab continuation (250 mg/m² iv weekly) will begin only if at least disease stabilization is observed at the end of chemotherapy, and will be continued until PD or unacceptable toxicity.

Drug: Cisplatin; Drug: 5-Fluorouracile; Drug: Cetuximab

TPEx: Cisplatin, Docetaxel and Cetuximab

EXPERIMENTAL

Chemotherapy: 4 cycles (every 3 weeks) of Cisplatin (75 mg/m² iv on Day1), Docetaxel (75 mg/m² iv on Day1), and Cetuximab (loading dose of 400 mg/m² iv on Day1, then 250 mg/m² iv weekly). If Cisplatin is not tolerated, cisplatin is replaced by carboplatin, AUC 5 (but not exceeding 750 mg), except in the case of bleeding tumor. Primary prophylactic administration of GCSF must be administered systematically after each cycle of chemotherapy. Cetuximab maintenance : cetuximab continuation (500 mg/m² iv every two weeks) will begin only if at least disease stabilization is observed at the end of chemotherapy, and will be continued until PD or unacceptable toxicity.

Drug: Cisplatin; Drug: Docetaxel; Drug: Cetuximab; Drug: granulocyte colony-stimulating factor (G-CSF)

Interventions

Cisplatin DRUG

EXTREME: Cisplatin, 5-FU and Cetuximab; TPEx: Cisplatin, Docetaxel and Cetuximab

5-Fluorouracile DRUG

EXTREME: Cisplatin, 5-FU and Cetuximab

Docetaxel DRUG

TPEx: Cisplatin, Docetaxel and Cetuximab

Cetuximab DRUG

EXTREME: Cisplatin, 5-FU and Cetuximab; TPEx: Cisplatin, Docetaxel and Cetuximab

granulocyte colony-stimulating factor (G-CSF) DRUG

TPEx: Cisplatin, Docetaxel and Cetuximab

Eligibility Criteria

• Age: 18 Years - 71 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis squamous cell carcinoma of head and neck: oral cavity, oropharynx, hypopharynx, larynx (histological confirmation is mandatory at least for initial diagnosis)
• Recurrence and/or metastatic disease not suitable for local therapy
• At least one measurable lesion (RECIST) by CT or MRI
• PS \< 2
• Age ≥ 18 years and \< 71 years
• Clearance of creatinine \> 60ml/mn (MDRD)
• Haematological function as follows: absolute neutrophil count \> 1.5 x 109/l, platelet \> 100 x 109/l, hemoglobin ≥ 9.5 g/dl
• Hepatic function as followed: bilirubin ≤ Upper limit of normal (ULN); SGOT/SGPT \< 1.5 ULN; AP \< 2.5 ULN
• Estimated life expectancy \> 12 weeks
• Informed Consent Form signed
• Affiliation to an health insurance
• Negative pregnancy test in women of childbearing potential within 14 days prior to treatment initiation (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization). Both men and women (of childbearing potential) who are sexually active must use adequate contraception, during and for at least 6 months post-treatment.

You may not qualify if:

• Patients with nasopharyngeal cancer, paranasal sinus cancer or unknown primary
• Prior systemic chemotherapy for the head and neck carcinoma, except if given as part of a multimodal treatment for locally advanced disease which was completed more than 6 months prior to study entry
• Surgery (excluding diagnostic biopsy) or radiotherapy within 6 weeks before study entry
• Contra-indication to receive cisplatin
• Known dihydropyrimidine dehydrogenase (DPD) deficiency
• Administration of prophylactic phenytoin
• Recent or planed yellow fever vaccination
• Prior dose of cisplatin \> 300 mg/m² (a patient who received prior RT + 3 cycles of cisplatin or 3 cycles induction TPF, i.e. total dose of cisplatin ≤ 300 mg/m², for locally advanced primary HN cancer can be included)
• Prior anti-EGFR treatment received less than 12 months before enrolment in the trial
• Known hypersensitivity reaction to 5FU, cisplatin, carboplatin, docetaxel or cetuximab
• Documented or symptomatic brain or leptomeningeal metastasis
• Clinically significant cardiovascular disease, e.g. cardiac failure of New York Heart Association classes III-IV, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled arrhythmia, uncontrolled hypertension, or history of myocardial infarction in the last 12 months
• Malignancies within 5 years prior to randomization, with the exception of adequately treated basal or squamous cell skin cancer and carcinoma in situ of the cervix
• Active infection (infection requiring IV antibiotics), including active tuberculosis and known and declared human immunodeficiency virus (HIV).
• Significant disease which, in the judgment of the investigator, would make the patient inappropriate for entry into the trial.

Sponsors & Collaborators

• Groupe Oncologie Radiotherapie Tete et Cou: lead
• Grupo Español de Tratamiento de Tumores de Cabeza y Cuello: collaborator
• AIO-Studien-gGmbH: collaborator

Study Sites (17)

Institut Sainte Catherine

Avignon, 84082, France

Location

Centre Hospitalier de la Dracénie

Draguignan, France

Location

Centre Médical de Forcilles

Férolles-Attilly, 77150, France

Location

Clinique des Ormeaux

Le Havre, 76600, France

Location

Centre Hospitalier de Bretagne Sud (CHBS)

Lorient, 56322, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Hôpital de la Timone

Marseille, 13385, France

Location

ICM Val d'Aurelle, Montpellier

Montpellier, 34298, France

Location

Centre Antoine-Lacassagne

Nice, 06189, France

Location

Val de Grace

Paris, 75005, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Institut de Cancérologie de l'Ouest (ICO) René Gauducheau

Saint-Herblain, 44805, France

Location

L'Institut de Cancérologie de Lorraine (ICL) Alexis Vautrin

Vandœuvre-lès-Nancy, 54511, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Charité Campus Benjamin Franklin

Berlin, 12203, Germany

Location

Instituto Catalá de Oncologia (ICO)

Barcelona, 08907, Spain

Location

Related Publications (2)

• Atsou K, Auperin A, Guigay J, Salas S, Benzekry S. Mechanistic Learning for Predicting Survival Outcomes in Head and Neck Squamous Cell Carcinoma. CPT Pharmacometrics Syst Pharmacol. 2025 Mar;14(3):540-550. doi: 10.1002/psp4.13294. Epub 2024 Dec 25.

  PMID: 39722558 DERIVED

• Guigay J, Auperin A, Fayette J, Saada-Bouzid E, Lafond C, Taberna M, Geoffrois L, Martin L, Capitain O, Cupissol D, Castanie H, Vansteene D, Schafhausen P, Johnson A, Even C, Sire C, Duplomb S, Evrard C, Delord JP, Laguerre B, Zanetta S, Chevassus-Clement C, Fraslin A, Louat F, Sinigaglia L, Keilholz U, Bourhis J, Mesia R; GORTEC; AIO; TTCC, and UniCancer Head and Neck groups. Cetuximab, docetaxel, and cisplatin versus platinum, fluorouracil, and cetuximab as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (GORTEC 2014-01 TPExtreme): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2021 Apr;22(4):463-475. doi: 10.1016/S1470-2045(20)30755-5. Epub 2021 Mar 5.

  PMID: 33684370 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Cisplatin; Fluorouracil; Docetaxel; Cetuximab; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Study Officials

• Joel GUIGAY, MD

  Centre Antoine Lacassagne, Nice, France

  STUDY CHAIR

• Jean BOURHIS, MD, PhD

  GORTEC President

  STUDY DIRECTOR

• Ricardo MESIA, MD

  Instituto Catalá de Oncologia (ICO), Barcelona, Spain

  PRINCIPAL INVESTIGATOR

• Ulrich KEILHOLZ, MD

  Charité Campus Benjamin Franklin, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2014
• First Posted: October 20, 2014
• Study Start: October 10, 2014
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: August 23, 2022

Record last verified: 2022-08

Locations

FR (15); DE (1); ES (1)