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Carcinoma, Squamous Cell of Head and NeckPhase 2NCT01538381

Neoadjuvant Afatinib Window Study in Squamous Cell Carcinoma of the Head and Neck

A Phase 2 study testing Afatinib and Observation in people with Carcinoma, Squamous Cell of Head and Neck, run by European Organisation for Research and Treatment of Cancer - EORTC at 4 sites in 2 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

The general objectives are to evaluate the pre-operative activity and the safety of afatinib in head and neck cancer and to explore the different downstream molecular pathways to identify tumor response and resistance mechanisms. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Afatinib and Observation
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
4 sitesin 2 countries
Study dates
Jul 2012to Aug 2015
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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 <or= 1.5 mg/dL (< 133 µmol/L) or calculated creatinine clearance ≥50 mL/min
  • Controlled blood pressure (<140/90 mm Hg) with or without antihypertensive treatment
  • Prothrombin time (PT) with an international normalized ratio (INR) <or=1.2
  • Partial thromboplastin time (PTT) <or= 1.2 times ULN
  • 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

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

Belgium3 sites

  • Institut Jules Bordet

    Brussels, 1000

  • Cliniques Universitaires St. Luc

    Brussels, 1200

  • U.Z. Leuven - Campus Gasthuisberg

    Leuven, 3000

Other trials in Belgium

Italy1 site

  • Istituto Nazionale Per Lo Studio E La Cura Dei Tumori

    Milan, 20133

Other trials in Italy

About this study

Official title: Neoadjuvant Afatinib Based Treatment Strategies Followed by Surgery in Squamous Cell Carcinoma of the Head and Neck: an EORTC NOCI-HNCG Window Study.

The general objectives are to evaluate the pre-operative activity and the safety of afatinib in head and neck cancer and to explore the different downstream molecular pathways to identify tumor response and resistance mechanisms. The results from this study can be used to conduct a larger trial that would allow us to confirm or validate the hypotheses generated.

Read the detailed description

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.

Being tested
Afatinib, Observation
Keywords
Neoadjuvant targeted therapy, Preoperative targeted therapy, Afatinib
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.

  • AfatinibDrug

    Afatinib for 2 weeks at a dose of 40 mg/day

  • ObservationOther

    Observation

Study groups in NCT01538381
Study groupRoleWhat they receive
AfatinibExperimentalAfatinib given orally for 2 weeks after randomization till day -1 prior to surgery (day 0) at a dose of 40 mg/day
Receives: Drug: Afatinib
ObservationOtherNo treatment only observation
Receives: Other: Observation

What is being measured

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

  1. Reduction of tumor Standardised Uptake Volume as assessed by FDGPET

    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

    Measured: Baseline and after two weeks of treatment

Secondary outcomes (1)

  1. Evaluation of tumour response to treatment by different imaging modalities like DWIMRI and DCEMRI

    Response after 2 weeks of treatment, prior to surgery, evaluated by:

    • RECIST v1.1 using conventional imaging
    • Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE MRI)
    • Diffusion Weighted Imaging Magnetic Resonance Imaging (DWI MRI)

    Measured: Baseline and after two weeks of treatment

Timeline

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

  1. First posted24 Feb 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionAug 2015
  4. Study completionAug 2015

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
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01538381
Sponsor's protocol ID
EORTC-90111-24111
Other IDs
2011-005820-17
Status last verified
Jul 2018
First submitted
20 Feb 2012
Last updated
9 Jul 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Beyaert SP, Loriot AE, Huyghe ND, Goebbels RM, Mendola A, Govaerts AS, Fortpied C, Baldin P, Licitra LF, Lalami Y, Clement PM, Machiels JH, Schmitz S. Tumor Microenvironment Modifications Induced by Afatinib in Squamous Cell Carcinoma of the Head and Neck: A Window-of-Opportunity Study (EORTC-90111-24111). Clin Cancer Res. 2023 Oct 13;29(20):4076-4087. doi: 10.1158/1078-0432.CCR-23-0645.

    PubMed 37531234

  • Machiels JP, Bossi P, Menis J, Lia M, Fortpied C, Liu Y, Lhommel R, Lemort M, Schmitz S, Canevari S, De Cecco L, Guzzo M, Bianchi R, Quattrone P, Crippa F, Duprez T, Lalami Y, Quiriny M, de Saint Aubain N, Clement PM, Coropciuc R, Hauben E, Licitra LF. Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN). Ann Oncol. 2018 Apr 1;29(4):985-991. doi: 10.1093/annonc/mdy013.

    PubMed 29346507

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Afatinib and Observation in people with Carcinoma, Squamous Cell of Head and Neck, run by European Organisation for Research and Treatment of Cancer - EORTC at 4 sites in 2 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 26 inclusion and 10 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 9 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Belgium, Italy. 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?

Reduction of tumor Standardised Uptake Volume as assessed by FDGPET (time frame: Baseline and after two weeks of 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 NCT01538381, which also lists 2 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 9 Jul 2018.

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