NCT01538381

Brief 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. The results from this study can be used to conduct a larger trial that would allow us to confirm or validate the hypotheses generated.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jul 2012

Typical duration for phase_2

Geographic Reach
2 countries

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 20, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

February 24, 2012

Completed
4 months until next milestone

Study Start

First participant enrolled

July 1, 2012

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2015

Completed
Last Updated

July 9, 2018

Status Verified

July 1, 2018

Enrollment Period

3.1 years

First QC Date

February 20, 2012

Last Update Submit

July 6, 2018

Conditions

Carcinoma, Squamous Cell of Head and Neck

Keywords

Neoadjuvant targeted therapyPreoperative targeted therapyAfatinib

Outcome Measures

Primary Outcomes (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

    Baseline and after two weeks of treatment

Secondary Outcomes (1)

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

    Baseline and after two weeks of treatment

Study Arms (2)

Afatinib

EXPERIMENTAL

Afatinib given orally for 2 weeks after randomization till day -1 prior to surgery (day 0) at a dose of 40 mg/day

Drug: Afatinib

Observation

OTHER

No treatment only observation

Other: Observation

Interventions

AfatinibDRUG

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

Afatinib
ObservationOTHER

Observation

Observation

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 \<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
  • +11 more criteria

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Cliniques Universitaires St. Luc

Brussels, 1200, Belgium

Location

U.Z. Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Istituto Nazionale Per Lo Studio E La Cura Dei Tumori

Milan, 20133, Italy

Location

Related Publications (1)

  • 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.

    PMID: 29346507DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

AfatinibObservation

Condition Hierarchy (Ancestors)

Carcinoma, Squamous CellCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsHead and Neck NeoplasmsNeoplasms by Site

Intervention Hierarchy (Ancestors)

AmidesOrganic ChemicalsQuinazolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsMethodsInvestigative Techniques

Study Officials

  • Jean-Pascal Machiels, MD

    European Organisation for Research and Treatment of Cancer - EORTC

    STUDY CHAIR

  • Lisa Licitra, MD

    European Organisation for Research and Treatment of Cancer - EORTC

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 20, 2012

First Posted

February 24, 2012

Study Start

July 1, 2012

Primary Completion

August 1, 2015

Study Completion

August 1, 2015

Last Updated

July 9, 2018

Record last verified: 2018-07

Locations

BE(3)IT(1)