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

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ClinicalTrials.gov Identifier: NCT02268695
Recruitment Status : Active, not recruiting
First Posted : October 20, 2014
Last Update Posted : February 16, 2018
Sponsor:
Collaborators:
Grupo Español de Tratamiento de Tumores de Cabeza y Cuello
AIO-Studien-gGmbH
Information provided by (Responsible Party):
Groupe Oncologie Radiotherapie Tete et Cou

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.

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Drug: Cisplatin Drug: 5-Fluorouracile Drug: Docetaxel Drug: Cetuximab Drug: granulocyte colony-stimulating factor (G-CSF) Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 416 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : October 2014
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: EXTREME: Cisplatin, 5-FU and Cetuximab

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
Experimental: TPEx: Cisplatin, Docetaxel and Cetuximab

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)



Primary Outcome Measures :
  1. Overall survival [ Time Frame: Until patient death or at least one year after the end of the treatment ]
    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.


Secondary Outcome Measures :
  1. Objective response rate [ Time Frame: At 12 weeks ]
    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).

  2. Best overall tumor response rate [ Time Frame: until progression or at least one year after the end of the treatment ]
    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

  3. Progression free survival [ Time Frame: until progression or death or at least one year after the end of the treatment ]
    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.

  4. Time to Progression [ Time Frame: until progression or death or at least one year after the end of the treatment ]
    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.

  5. Toxicity [ Time Frame: until the end of the maintenance, an expected average of 4 months of maintenance ]
    Toxicity (according to CTC-NCI V4): all grades

  6. Compliance [ Time Frame: until the end of the maintenance, an expected average of 4 months of maintenance ]
    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.

  7. EORTC QLQ-C30 [ Time Frame: At baseline before treatment, at Week 12, Week 18 and at Week 26 ]
    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

  8. EuroQol-5D [ Time Frame: 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 ]
    Quality-adjusted life-years (QALYs) based on Euroqol EQ-5D measurements

  9. Net monetary benefit [ Time Frame: until death or at least one year after the end of the treatment ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 71 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02268695


Locations
France
Institut Sainte Catherine
Avignon, France, 84082
Centre Hospitalier de la Dracénie
Draguignan, France
Centre Médical de Forcilles
Férolles-Attilly, France, 77150
Clinique des Ormeaux
Le Havre, France, 76600
Centre Hospitalier de Bretagne Sud (CHBS)
Lorient, France, 56322
Centre Léon Bérard
Lyon, France, 69008
Hôpital de la Timone
Marseille, France, 13385
ICM Val d'Aurelle, Montpellier
Montpellier, France, 34298
Centre Antoine-Lacassagne
Nice, France, 06189
Val de Grace
Paris, France, 75005
Centre Eugene Marquis
Rennes, France, 35042
Centre Henri Becquerel
Rouen, France, 76038
Institut de Cancérologie de l'Ouest (ICO) René Gauducheau
Saint Herblain, France, 44805
L'Institut de Cancérologie de Lorraine (ICL) Alexis Vautrin
Vandoeuvre les Nancy, France, 54511
Gustave Roussy
Villejuif, France, 94805
Germany
Charité Campus Benjamin Franklin
Berlin, Germany, 12203
Spain
Instituto Catalá de Oncologia (ICO)
Barcelona, Spain, 08907
Sponsors and Collaborators
Groupe Oncologie Radiotherapie Tete et Cou
Grupo Español de Tratamiento de Tumores de Cabeza y Cuello
AIO-Studien-gGmbH
Investigators
Study Chair: Joel GUIGAY, MD Centre Antoine Lacassagne, Nice, France
Study Director: Jean BOURHIS, MD, PhD GORTEC President
Principal Investigator: Ricardo MESIA, MD Instituto Catalá de Oncologia (ICO), Barcelona, Spain
Principal Investigator: Ulrich KEILHOLZ, MD Charité Campus Benjamin Franklin, Berlin, Germany

Responsible Party: Groupe Oncologie Radiotherapie Tete et Cou
ClinicalTrials.gov Identifier: NCT02268695     History of Changes
Other Study ID Numbers: GORTEC 2014-01
First Posted: October 20, 2014    Key Record Dates
Last Update Posted: February 16, 2018
Last Verified: February 2018

Keywords provided by Groupe Oncologie Radiotherapie Tete et Cou:
Recurrent/Metastatic HNSCC
Taxanes

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Docetaxel
Cisplatin
Cetuximab
Lenograstim
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs