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

Head and Neck Squamous Cell Carcinoma Clinical Trial

— TPExtreme  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02268695
• Other study ID #: GORTEC 2014-01
• Status: Completed
• Phase: Phase 2
• Start date: October 10, 2014
• Est. completion date: December 31, 2021

Study information

• Verified date: August 2022
• Source: Groupe Oncologie Radiotherapie Tete et Cou
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 541
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 71 Years

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Cisplatin

• 5-Fluorouracile

• Docetaxel

• Cetuximab

• granulocyte colony-stimulating factor (G-CSF)

Locations

Country	Name	City	State
France	Institut Sainte Catherine	Avignon
France	Centre Hospitalier de la Dracénie	Draguignan
France	Centre Médical de Forcilles	Férolles-Attilly
France	Clinique des Ormeaux	Le Havre
France	Centre Hospitalier de Bretagne Sud (CHBS)	Lorient
France	Centre Léon Bérard	Lyon
France	Hôpital de la Timone	Marseille
France	ICM Val d'Aurelle, Montpellier	Montpellier
France	Centre Antoine-Lacassagne	Nice
France	Val de Grace	Paris
France	Centre Eugene Marquis	Rennes
France	Centre Henri Becquerel	Rouen
France	Institut de Cancérologie de l'Ouest (ICO) René Gauducheau	Saint Herblain
France	L'Institut de Cancérologie de Lorraine (ICL) Alexis Vautrin	Vandoeuvre les Nancy
France	Gustave Roussy	Villejuif
Germany	Charité Campus Benjamin Franklin	Berlin
Spain	Instituto Catalá de Oncologia (ICO)	Barcelona

Sponsors (3)

Lead Sponsor	Collaborator
Groupe Oncologie Radiotherapie Tete et Cou	AIO-Studien-gGmbH, Grupo Español de Tratamiento de Tumores de Cabeza y Cuello

Countries where clinical trial is conducted

France,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Objective response rate	Objective response rate (complete response (CR) or partial response (PR) according to RECIST 1.1 criteria and assessed by central imaging review) at 12 weeks. For the statistical analysis patients not evaluable (whatever the reason, including death) will be considered as failure (i.e. no CR, no PR).	At 12 weeks
Secondary	Best overall tumor response rate	Best overall tumor response rate (RECIST 1.1 criteria) during chemotherapy and maintenance: CR or PR or SD confirmed for CR or PR by a second assessment 6 weeks later	until progression or at least one year after the end of the treatment
Secondary	Progression free survival	Progression free survival (PFS): minimum time from randomization to progression as defined by RECIST 1.1 criteria or to death from any cause. Patients who don't have any of these events are censored at the date of last follow-up.	until progression or death or at least one year after the end of the treatment
Secondary	Time to Progression	Time to Progression (TTP): minimum time from randomization to progression as defined by RECIST 1.1 criteria. In case of death from other cause than cancer and no prior progression, the patient will be censored at the time of death. In case of death related to cancer without an accurate date of progression before death, the patient will be considered in progression at the time of death. In the event of no progression and no death, the patient will be censored at the date of last follow-up.	until progression or death or at least one year after the end of the treatment
Secondary	Toxicity	Toxicity (according to CTC-NCI V4): all grades	until the end of the maintenance, an expected average of 4 months of maintenance
Secondary	Compliance	Compliance: Insufficient compliance for cetuximab is defined as a patient missing more than 2 consecutive infusions of cetuximab, even if the missed infusions are due to toxicity. Insufficient compliance for chemotherapy is defined as a patient missing more than 2 consecutive infusions of chemotherapy, even if the missed infusions are due to toxicity.	until the end of the maintenance, an expected average of 4 months of maintenance
Secondary	EORTC QLQ-C30	Health related quality of life (QoL) assessed by EORTC QLQ-C30. The primary endpoint of the QoL study is the global health status/quality of-life scale of the QLQ-C30 questionnaire	At baseline before treatment, at Week 12, Week 18 and at Week 26
Secondary	EuroQol-5D	Quality-adjusted life-years (QALYs) based on Euroqol EQ-5D measurements	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
Secondary	Net monetary benefit		until death or at least one year after the end of the treatment