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Head and Neck Squamous Cell CarcinomaPhase 2TPExtremeNCT02268695

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

A Phase 2 study testing Cisplatin, 5-Fluorouracile and Docetaxel in people with Head and Neck Squamous Cell Carcinoma, run by Groupe Oncologie Radiotherapie Tete et Cou at 17 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 71 years
Conditions the study is for
Head and Neck Squamous Cell Carcinoma
What is being tested?
Cisplatin, 5-Fluorouracile and Docetaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
541 participants
Where
17 sitesin 3 countries
Study dates
10 Oct 2014to 31 Dec 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 71 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

17 sites in 3 countries.

17 sites in 3 countries

France15 sites
  • Institut Sainte Catherine

    Avignon, 84082

  • Centre Hospitalier de la Dracénie

    Draguignan

  • Centre Médical de Forcilles

    Férolles-Attilly, 77150

  • Clinique des Ormeaux

    Le Havre, 76600

  • Centre Hospitalier de Bretagne Sud (CHBS)

    Lorient, 56322

  • Centre Léon Bérard

    Lyon, 69008

  • Hôpital de la Timone

    Marseille, 13385

  • ICM Val d'Aurelle, Montpellier

    Montpellier, 34298

  • Centre Antoine-Lacassagne

    Nice, 06189

  • Val de Grace

    Paris, 75005

  • Centre Eugene Marquis

    Rennes, 35042

  • Centre Henri Becquerel

    Rouen, 76038

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

    Saint-Herblain, 44805

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

    Vandœuvre-lès-Nancy, 54511

  • Gustave Roussy

    Villejuif, 94805

Other trials in France

Germany1 site
  • Charité Campus Benjamin Franklin

    Berlin, 12203

Other trials in Germany

Spain1 site
  • Instituto Catalá de Oncologia (ICO)

    Barcelona, 08907

Other trials in Spain

About this study

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

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.

Read the 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.

Being tested
Cisplatin, 5-Fluorouracile, Docetaxel, Cetuximab, granulocyte colony-stimulating factor (G-CSF)
Keywords
Recurrent/Metastatic HNSCC, Taxanes
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02268695
Study groupRoleWhat they receive
EXTREME: Cisplatin, 5-FU and CetuximabActive comparatorChemotherapy: 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.
Receives: Drug: Cisplatin; Drug: 5-Fluorouracile; Drug: Cetuximab
TPEx: Cisplatin, Docetaxel and CetuximabExperimentalChemotherapy: 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.
Receives: Drug: Cisplatin; Drug: Docetaxel; Drug: Cetuximab; Drug: granulocyte colony-stimulating factor (G-CSF)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (9)
  1. 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).

    Measured: At 12 weeks

  2. 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

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

  3. 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.

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

  4. 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.

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

  5. Toxicity

    Toxicity (according to CTC-NCI V4): all grades

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

  6. 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.

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

  7. 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

    Measured: At baseline before treatment, at Week 12, Week 18 and at Week 26

  8. EuroQol-5D

    Quality-adjusted life-years (QALYs) based on Euroqol EQ-5D measurements

    Measured: 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

  9. Net monetary benefit

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Oct 2014 (estimated)
  2. Study start10 Oct 2014
  3. Primary completion31 Dec 2021
  4. Study completion31 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
541 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02268695
Sponsor's protocol ID
GORTEC 2014-01
Acronym
TPExtreme
Status last verified
Aug 2022
First submitted
13 Oct 2014
Last updated
23 Aug 2022
Results posted
No
Data monitoring committee
Yes

Publications

  • Fraslin AM, Auperin A, Even C, Fayette J, Saada-Bouzid E, Lafond C, Geoffrois L; TPExtreme-ECO Group; Bourhis J, Guigay J, Bonastre J. Cost-Utility Analysis Alongside the GORTEC 2014-01 TPExtreme Trial: TPEx Versus EXTREME as First-Line Treatment in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Value Health. 2025 Dec;28(12):1793-1801. doi: 10.1016/j.jval.2025.07.032. Epub 2025 Aug 21.

    PubMed 40848743
  • 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.

    PubMed 39722558
  • 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.

    PubMed 33684370

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cisplatin, 5-Fluorouracile and Docetaxel in people with Head and Neck Squamous Cell Carcinoma, run by Groupe Oncologie Radiotherapie Tete et Cou at 17 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in France, Germany, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (time frame: Until patient death or at least one year after the end of the treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02268695, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2022.

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