Neoadjuvant Afatinib Based Treatment Strategies Followed by Surgery in Squamous Cell Carcinoma of the Head and Neck: an EORTC NOCI-HNCG Window Study.
18 Years
N/A
Both
Carcinoma, Squamous Cell of Head and Neck
Trial Information
Neoadjuvant Afatinib Based Treatment Strategies Followed by Surgery in Squamous Cell Carcinoma of the Head and Neck: an EORTC NOCI-HNCG Window Study.
This is a randomized, multicenter early phase II trial exploring the pre-operative activity
of afatinib vs. nontreatment. The study includes an early monitoring of the surgical
co-morbidities for patients treated with afatinib and accrual may be stopped prematurely
according to a pre-defined safety stopping rule.
Patients will be randomized with a 5:1 ratio, between the two arms: afatinib and 'no
treatment'. It is intended to include a total of 30 eligible patients out of which 25
patients will be randomized into the afatinib arm.
Patients allocated to the 'no treatment' arm will mainly serve as a reference to interpret
the results of the translational research part of the study although no formal comparison
between the afatinib arm and the 'no treatment' arm is intended.
Patients will be first registered into the EORTC system after signing the informed consent
form. The site will have to complete all the study related procedures within 4 weeks prior
randomization and all eligibility criteria should be met before the patient can be
randomized into the study.
The registration of patients will proceed with slots for patients which will be opened or
closed based on the randomization of patients into the afatinib arm. Starting with 3 free
slots, an additional slot will become available for each patient randomized to the 'no
treatment' arm.
Registration will be paused after three completes the 4 week observation period after
surgery. Similar action will be done after the next 3 patients have been entered into the
afatinib arm.
Once the first 6 patients in the afatinib arm have been observed for surgical toxicities of
grade ≥ 3 for 4 weeks following surgery, the slot system will cease to operate.
Inclusion Criteria:
- Newly diagnosed histologically proven squamous cell carcinoma of the oral cavity,
oropharynx, hypopharynx or larynx.
- Patients selected for a primary surgical treatment
- Age ≥18 years
- Performance status ECOG 0-1
- Within 2 weeks prior randomization:
- Adequate bone marrow function as demonstrated by neutrophils count ≥ 1,500/mm3,
platelet count ≥ 75,000/mm3, WBC ≥ 3.0/109 L
- Adequate hepatic function as demonstrated by bilirubin < 2 times upper limit of
normal (ULN), ALAT or ASAT < 3 times ULN
- Adequate renal function as demonstrated by serum creatinine
- Controlled blood pressure (<140/90 mm Hg) with or without antihypertensive
treatment
- Prothrombin time (PT) with an international normalized ratio (INR)
- Partial thromboplastin time (PTT)
- Adequate cardiac function assessed by 12-lead ECG and if clinically indicated
echocardiography to document LVEF
- FDG-PET/CT performed
- DCE MRI and DWI MRI performed
- Primary tumor ≥2 cm in their largest diameter measured bidimensionally by imaging
done within 2 weeks prior to randomization
- Availability of tumor and normal mucosa biopsies during staging endoscopy (please
refer to surgical guidelines for further information).
- Availability of blood samples for translational research
- Absence of any serious underlying medical conditions which could impair the ability
of the patient to participate in the study
- Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and 6 months beyond stop of
treatment in such a manner that the risk of pregnancy is minimized. In general, the
decision for appropriate methods to prevent pregnancy should be determined by
discussions between the investigator and the study subject. WOCBP include any female
who has experienced menarche and who has not undergone successful surgical
sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or
is not postmenopausal. Females should not be breast feeding.
- Post menopause is defined as: amenorrhea ≥ 12 consecutive months without another
cause or for women with irregular menstrual periods and on hormone replacement
therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35
mIU/mL
- Women who are using oral contraceptives, other hormonal contraceptives (vaginal
products, skin patches, or implanted or injectable products), or mechanical
products such as an intrauterine device or barrier methods (diaphragm, condoms,
spermicide) to prevent pregnancy, or are practicing abstinence or where their
partner is sterile (e.g., vasectomy) should be considered to be of childbearing
potential.
- Women of child bearing potential must have a negative serum or urine pregnancy
test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours
prior to the start of investigational product.
- Female patients within one year of entering the menopause must agree to use an
effective non-hormonal method of contraception during the treatment period and
for at least 6 months after the last study treatment.
- Males must agree to use an effective method of contraception during the treatment
period and for at least 6 months after the last study treatment.
- Absence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule;
those conditions should be discussed with the patient before registration in the
trial
- Before patient registration, written informed consent must be given according to
ICH/GCP, and national/local regulations
Exclusion Criteria:
- Patients with nasopharynx, nasal cavity and paranasal sinuses carcinomas, or
recurrent/metastatic SCCHN are not eligible for this study
- T3 -T4 hypopharyngeal SCCHN are excluded.
- Distant metastases
- Active second malignancy during the last five years except non melanomatous skin
cancer or carcinoma in situ of the cervix
- Prior chemotherapy, radiotherapy or targeted therapy including HER inhibitors
(monoclonal antibodies or tyrosine kinase inhibitors) for SCCHN
- Concomitant use of potent P-gp inhibitors, potent P-gp inducers or Erythropoietin
(EPO)
- Evidence of diabetes
- Evidence of interstitial lung disease
- Weight loss of more than 10% in the previous 6 months
- Participation in another interventional clinical trial in the preceding 30 days prior
to randomization
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Reduction of tumor Standardised Uptake Volume as assessed by FDGPET
Outcome Description:
Afatinib will be given orally for 2 weeks from the day of randomization until day -1 prior to surgery at a dose of 40 mg/day.Pre-treatment biopsies and blood samples will be harvested during the regular diagnosis staging procedure and at surgery.FDG-PET/CT-scan and MRIs will be performed before treatment (before day -15) and the day before surgery.The primary outcome measure is the reduction in the tumor standardised uptake volume as assessed by FDGPET
Outcome Time Frame:
Baseline and after two weeks of treatment
Safety Issue:
No
Principal Investigator
Jean-Pascal Machiels, MD
Investigator Role:
Study Chair
Investigator Affiliation:
European Organisation for Research and Treatment of Cancer - EORTC
Authority:
Belgium: Federal Agency for Medicinal Products and Health Products
Study ID:
EORTC-90111-24111
NCT ID:
NCT01538381
Start Date:
July 2012
Completion Date:
December 2013
Related Keywords:
- Carcinoma, Squamous Cell of Head and Neck
- Neoadjuvant targeted therapy
- Preoperative targeted therapy
- Afatinib
- Carcinoma
- Carcinoma, Squamous Cell
- Head and Neck Neoplasms
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