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Evaluation of the Tolerance of Afatinib in Combination With Docetaxel and Cisplatin in LAHNSCC Induction Chemotherapy (TAPIS)

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ClinicalTrials.gov Identifier: NCT02216617
Recruitment Status : Completed
First Posted : August 15, 2014
Last Update Posted : October 27, 2017
Sponsor:
Information provided by (Responsible Party):
Groupe Oncologie Radiotherapie Tete et Cou

Brief Summary:

The purpose of the study is to determine the maximum tolerated dose (MTD) of afatinib administrated in combination with docetaxel (Taxotere®) and cisplatin in induction chemotherapy of locally advanced head and neck carcinoma in order to move to a phase II, allowing the comparison with standard induction chemotherapy TPF.

It is a multicentric, national, opened, not-randomized phase Ib. Three doses of afatinib (20, 30 and 40 Mg per day) will be studied in combination with the fixed standard doses of docetaxel and cisplatin. For each dose level, beginning with smallest (20 Mg per day of afatinib), 3 to 6 patients will be treated at maximum, i.e. 3 cycles of three weeks treatment each one (9 weeks on the whole). The next dose level will be studied only if the previous dose is well tolerated for the period of the first 4 weeks observation of the treatment (1st cycle more first week of the 2nd cycle). Once the MTD is determined, four additional patients will be treated with this dose. A maximum of 22 patients should be included in this study. The total duration of the study is estimated at 18 months. In case of major safety problems, the study may be stopped earlier. In short, the preclinical data, pharmacological and clinical on afatinib indicate that the benefit-risk ratio can be regarded as positive and that the association of afatinib with cisplatin and docetaxel could be effective in patients with head and neck squamous cell carcinoma potentially resulting in an extension of time to progression.


Condition or disease Intervention/treatment Phase
HNSCC Drug: Taxotere, Cisplatin, Afatinib Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study Evaluating the Combination Afatinib With Docetaxel and Cisplatin (TPA) in Induction Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Upper Aerodigestive Tract
Study Start Date : August 6, 2014
Actual Primary Completion Date : July 2015
Actual Study Completion Date : September 15, 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Induction chemotherapy TPA

3 Cycles of induction chemotherapy TPA : (Taxotere, Cisplatin, Afatinib)

1 cycle = 3 weeks, three cycles of treatment in total (or 9 weeks)

Docetaxel 75 mg / m2 at D1 Cisplatin 75 mg / m 2 at D1 Afatinib: x mg / day D2 to D21 by level: (Level 1: 20 mg / day; Level 2: 30 mg / day; Level 3: 40 mg / day)

Drug: Taxotere, Cisplatin, Afatinib



Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: During the first 4 weeks of treatment for each patient of the bearing. ]
    The main objective is to determine the Maximum Tolerated Dose (MTD) of afatinib in combination with docetaxel and cisplatin chemotherapy TPA induction in locally advanced head and neck carcinomas in order to move a phase II for comparison with induction chemotherapy "of reference "TPF (Taxotere, cisplatin and 5-fluorouracil).


Secondary Outcome Measures :
  1. Tolerance [ Time Frame: 12 weeks ]
    Tolerance: Toxicity will be evaluated by NCI CTCAE V4.03. scale

  2. Efficacy [ Time Frame: 12 weeks ]
    Efficacy: Objective tumor response will be evaluated through RECIST V1.1


Other Outcome Measures:
  1. Correlation between nutritional status and toxicity [ Time Frame: 12 weeks ]
    Objective is to correlate the values of body fat / lean mass determined by CT-scan to the nutritional status of the patients and toxicities.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years and ≤70 years
  • Patient in first line treatment of Locally Advanced HNSCC, histologically proven non-metastatic
  • At least one measurable lesion (RECIST)
  • Eligible patient for standard induction chemotherapy in the opinion of the investigator; PS ECOG < 2

Adequacy functioning of organs, including:

  • Left ventricular function with ejection fraction at rest > 50% or as normal institutional values Haematological function
  • Absolute neutrophil count (ANC) >1,500/mm3 Special cases: ANC> 1,000/mm3 in the opinion of the investigator and discussion with the sponsor; Platelets ≥ 75,000/mm3; Hemoglobin> 10g/dl

Liver function:

•Total bilirubin ≤ 1.5 x ULN; patients with Gilbert's syndrome must have a total bilirubin <4 x ULN; SGOT and SGPT ≤ 3 x ULN or SGOT and SGPT ≤ 5 x ULN in case liver abnormalities; Alkaline phosphatase <2.5 x ULN

Kidney function:

•Serum creatinine <110 umol/L or creatinine clearance > 45 ml/min (Cockcroft method)

General:

  • Men and women of childbearing potential must agree to use a reliable contraception throughout treatment and at least 6 months after the end of treatment. Women in peri-menopause should be least 24 months of amenorrhea.
  • Ability to take oral medication in the opinion of the investigator; Patient affiliated to a social security system; signed informed consent form.

Exclusion Criteria:

•Previous treatment with chemotherapy, radiation therapy or targeted therapy for head and neck cancer; uncontrolled Respiratory, cardiac, hepatic or renal diseases.

Significant cardiovascular disease like:

  • Cardiovascular Abnormalities considered clinically important as congestive heart failure NYHA stage ≥ III, unstable angina or myocardial infarction within the past 6 months, or arrhythmia low controlled, uncontrolled hypertension by treatment (systolic BP ≥ 160 mmHg and/or diastolic BP≥ 90 mmHg).
  • Impairment of left ventricular function with an ejection fraction ≤ 50%; Stroke within 6 months prior to inclusion.
  • Severe thromboembolic history within 6 months prior to inclusion.
  • Lengthening of the corrected QT interval with QTc> 480 msec according to the formula Bazet; Bradycardia; Electrolyte disturbances

Respiratory disease of type:

•interstitial lung disease; Pulmonary fibrosis

Viral disease of type:

•Active infection or hepatic B virus or hepatitis C known carrier of HIV.

Recent digestive disorder with diarrhea such as:

  • Any history or presence of gastrointestinal disorders with uncontrolled diarrhea as a major symptom that may affect the absorption of drug tested in the opinion of the investigator (eg disease Crohn's disease, diarrhea CTCAE grade ≥ 2)
  • Any past or present condition that would compromise the patient's ability to comply with the study or which would interfere with the evaluation of the effectiveness and the safety of the study.
  • Other severe disease or condition associated with non-oncological origin likely to be incompatible with the protocol in the judgment of the investigator.
  • Patient already included in another clinical trial with an experimental molecule; Persons deprived of liberty or under guardianship or as backup justice.
  • Patient requiring prohibited concomitant treatments with study.
  • Any cons-indication to treatment with Taxotere or Afatinib or cisplatin.
  • Known hypersensitivity to Afatinib or excipients the study drugs; Major surgery within 4 weeks before taking treatment; Use of products in a clinical study during the 4 weeks preceding inclusion.

Radiation therapy within 4 weeks before inclusion.

•Presence and / or history (in the past 3 years) cancer except Basal cell skin cancer, cervical carcinoma in situ and prostate cancer in situ; Pregnant or during breastfeeding.


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): NCT02216617


Locations
France
ICM Val d'Aurelle, Montpellier
Montpellier, France, 34298
Sponsors and Collaborators
Groupe Oncologie Radiotherapie Tete et Cou
Investigators
Study Chair: Didier CUPISSOL, MD GORTEC

Additional Information:
Responsible Party: Groupe Oncologie Radiotherapie Tete et Cou
ClinicalTrials.gov Identifier: NCT02216617     History of Changes
Other Study ID Numbers: GORTEC 2013-01
2013-002876-42 ( EudraCT Number )
First Posted: August 15, 2014    Key Record Dates
Last Update Posted: October 27, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Docetaxel
Cisplatin
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action