Clinical trial NCT02268695: Platinum-Cetuximab Combined With Docetaxel or With 5FU in Patients With Recurrent/Metastatic HNSCC
Official title: TPExtreme: Randomized, Controlled Trial of Platinum-Cetuximab Combined Either With Docetaxel (TPEx) or With 5FU (Extreme) in Patients With Recurrent/Metastatic Squamous Cell Cancer of the Head and Neck
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Keywords: Recurrent/Metastatic HNSCC
Taxanes
Lead sponsor: Groupe Oncologie Radiotherapie Tete et Cou
Sponsor class: OTHER
Collaborators: name: Grupo Español de Tratamiento de Tumores de Cabeza y Cuello
name: AIO-Studien-gGmbH
First posted: 2014-10-20
Enrollment: 541
Sex: ALL
Minimum age (years): 18
Maximum age (years): 71
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The EXTREME regimen, i.e. cetuximab added to platinum (100 mg/m² every 3 weeks ) and 5FU (96h continuous infusion at 1000 mg/m²/day every 3 weeks) during 6 cycles of treatment and continued as maintenance in patients with stable disease, is currently the standard of care in first line recurrent metastatic HNSCC.

From our previous experience (phase II GORTEC "TPEx" study), the TPEx regimen of 4 cycles of docetaxel-cisplatin-cetuximab followed by maintenance with cetuximab every 2 weeks seems more efficient (overall survival) compared to EXTREME regiment. Docetaxel combined with cisplatine (each administered at 75mg/m² every 3 weeks) also appeared more convenient than the standard Cisplatin-5FU-Cetuximab EXTREME regimen (4 cycles of chemotherapy instead of 6 cycles and no i.v. continuous infusion). Toxicity was manageable with G-CSF support. In addition the toxicity / efficacy profile also seems favourable as suggested by the excellent dose intensity achieved and the high rate of patients (78%) who were able to start maintenance therapy.

Taking together all these considerations, the TPEx regimen might be a good substitute for EXTREME as first-line treatment in patients with recurrent metastatic HNSCC, and it is justified and necessary to perform a direct comparison in a randomized trial to further test this hypothesis.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* Any social, personal, medical and/or psychologic factor(s) that could interfere with the observance of the patient to the protocol and/or the follow-up and/or the signature of the informed consent.
* Pregnant or breast feeding women

Primary outcomes:
measure: Overall survival
timeFrame: Until patient death or at least one year after the end of the treatment
Secondary outcomes:
measure: Objective response rate
timeFrame: At 12 weeks
measure: Best overall tumor response rate
timeFrame: until progression or at least one year after the end of the treatment
measure: Progression free survival
timeFrame: until progression or death or at least one year after the end of the treatment
measure: Time to Progression
timeFrame: until progression or death or at least one year after the end of the treatment
measure: Toxicity
timeFrame: until the end of the maintenance, an expected average of 4 months of maintenance
measure: Compliance
timeFrame: until the end of the maintenance, an expected average of 4 months of maintenance
measure: EORTC QLQ-C30
timeFrame: At baseline before treatment, at Week 12, Week 18 and at Week 26
measure: EuroQol-5D
timeFrame: At baseline before treatment, at Week 12, at Week 26 and then every 2 months.until death or at least one year after the end of the treatment
measure: Net monetary benefit
timeFrame: until death or at least one year after the end of the treatment
Other outcomes:
Locations:
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Draguignan
country: France
facility: Centre Hospitalier de la Dracénie
city: Férolles-Attilly
country: France
facility: Centre Médical de Forcilles
city: Le Havre
country: France
facility: Clinique des Ormeaux
city: Lorient
country: France
facility: Centre Hospitalier de Bretagne Sud (CHBS)
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hôpital de la Timone
city: Montpellier
country: France
facility: ICM Val d'Aurelle, Montpellier
city: Nice
country: France
facility: Centre Antoine-Lacassagne
city: Paris
country: France
facility: Val de Grace
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Herblain
country: France
facility: Institut de Cancérologie de l'Ouest (ICO) René Gauducheau
city: Vandoeuvre les Nancy
country: France
facility: L'Institut de Cancérologie de Lorraine (ICL) Alexis Vautrin
city: Villejuif
country: France
facility: Gustave Roussy
city: Berlin
country: Germany
facility: Charité Campus Benjamin Franklin
city: Barcelona
country: Spain
facility: Instituto Catalá de Oncologia (ICO)
Study officials:
affiliation: Centre Antoine Lacassagne, Nice, France
name: Joel GUIGAY, MD
role: STUDY_CHAIR
affiliation: GORTEC President
name: Jean BOURHIS, MD, PhD
role: STUDY_DIRECTOR
affiliation: Instituto Catalá de Oncologia (ICO), Barcelona, Spain
name: Ricardo MESIA, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Charité Campus Benjamin Franklin, Berlin, Germany
name: Ulrich KEILHOLZ, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.