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Research of Biomarkers of Activity and Efficacy of BIBW2992 in Untreated Non-metastatic HNSCC Patients (PREDICTOR)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by UNICANCER
Sponsor:
Information provided by (Responsible Party):
UNICANCER
ClinicalTrials.gov Identifier:
NCT01415674
First received: August 10, 2011
Last updated: September 2, 2013
Last verified: September 2013
  Purpose

The purpose of this study is to identify predictive and pharmacodynamic biomarkers of activity and efficacy of pre-operative Afatinib (BIBW2992) in untreated non-metastatic head and neck squamous cell carcinoma patients


Condition Intervention Phase
Carcinoma, Squamous Cell of Head and Neck
Drug: Afatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multi-centric Randomized Phase II Study of Pre-operative Afatinib (BIBW2992) Aiming at Identifying Predictive and Pharmacodynamic Biomarkers of Biological Activity and Efficacy in Untreated Non-metastatic Head and Neck Squamous Cell Carcinoma Patients

Resource links provided by NLM:


Further study details as provided by UNICANCER:

Primary Outcome Measures:
  • Potential predictive biological markers of activity of Afatinib [ Time Frame: 15 days (FDG-PET evaluation) and about 21 days (CT scan or MRI evaluation) after start of treatment ] [ Designated as safety issue: No ]

    Correlation between baseline potential biomarkers and

    1. radiological response to Afatinib
    2. FDG-PET response to Afatinib

    To identify the predictive biomarkers, the following translational researches will be carried out on initial tumor biopsy

    • IHC tumour characterization
    • High throughput protein analysis
    • Molecular analyses : FISH , Mutations by PCR , Quantitative RT-PCR


Secondary Outcome Measures:
  • Potential pharmacodynamic biological markers of activity of Afatinib [ Time Frame: 15 days (FDG-PET evaluation) and about 21 days (CT scan or MRI evaluation) after start of treatment ] [ Designated as safety issue: No ]

    Correlation between down- or up-regulation of potential biomarkers (in pre-treatment biopsy and surgical specimen) and

    1. radiological response to Afatinib
    2. FDG-PET response to Afatinib

    To identify the pharmacodynamic biomarkers, the following translational researches will be carried out on initial tumor biopsy and surgical specimen

    • IHC tumour characterization
    • High throughput protein analysis
    • Molecular analyses : FISH , Mutations by PCR , Quantitative RT-PCR

  • Efficacy of Afatinib [ Time Frame: about 21 days (CT scan or MRI evaluation) after start of treatment ] [ Designated as safety issue: No ]
    - Efficacy will be defined as the tumour reduction between the baseline and the surgery (end of treatment). The radiological response will be assessed on CT/MRI of the head and neck. Tumour size will be the sum of 2 target lesions following the measurement rules from the RECIST 1.1. Noteworthy, a lymph node can be considered a target lesion only if its smallest diameter is ≥15 mm (according to RECIST 1.1). Measurement of a lymph node consists in measuring its smallest diameter (according to RECIST 1.1).

  • Toxicity of Afatinib [ Time Frame: every week until surgery. ] [ Designated as safety issue: Yes ]
    Toxicity will be assessed according to NCI CTC-AE v4.0 criteria

  • Pathological response [ Time Frame: on the surgical specimen ] [ Designated as safety issue: No ]
    Complete pathological response is defined as the absence of invasive cancer cells on the surgical specimen in the primary tumor and in lymph nodes.


Estimated Enrollment: 60
Study Start Date: January 2012
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Afatinib 40mg per os daily
Patients randomized to the arm A will take a single oral dose of Afatinib from Day 1, for 14 to 28 days, depending on the date of surgery. The number of dosing days will be chosen so that patients are off treatment for a maximum of 7 days before surgery.
Drug: Afatinib
Afatinib 40mg per os daily for 14 to 28 days, depending on the date of the surgery
Other Name: BIBW2992
No Intervention: Arm B : No pre operative treatment

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 18 years
  • Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx, previously untreated, amenable to curative treatment with surgery. Patients with a diagnosis of SCCHN of occult primary may be enrolled only with the agreement of the lead investigator upon review of the relevant clinical records
  • T2-4N0-2 tumors (except T2N0 endolaryngeal tumors)
  • Absence of metastases determined by PET CT scan
  • Planned date of surgery allowing the patient to receive between 21 and 28 days of treatment
  • ECOG performance status ≤ 2
  • Adequate bone marrow function (absolute neutrophil count > 1,000 cells/mm3, platelets > 75,000 cells/mm3)
  • Adequate liver function (total bilirubin ≤ 1.5 x UNL [upper normal limit], AST or ALT ≤ 3 x UNL)
  • Adequate renal function (serum creatinine ≤ 1.5 x UNL)
  • Adequate cardiac function (a normal left ventricular ejection fraction [LVEF] of ≥ 50% as measured by MUGA scan or echocardiogram within 4 weeks prior to start of study treatment)
  • Potentially reproductive patients must agree to use an effective contraceptive method while on treatment
  • Women of childbearing potential must have a negative serum beta-HCG pregnancy test within 7 days prior of enrollment and/or urine pregnancy 48 hours prior to the administration of the first study treatment
  • Patients must be able to swallow tablets
  • Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
  • Patients must be affiliated to a Social Security System
  • Patient information and written informed consent form signed

Exclusion Criteria:

  • Primary site of head and neck carcinoma in nasopharynx, or skin
  • T1N0 tumors and T2N0 endolaryngeal tumors
  • Patients not candidate for primary curative surgery
  • Planning of surgery not allowing the patient to receive 21 to 28 days of treatment
  • Patients receiving other anti-cancer medication such as chemotherapy, immunotherapy, biologic therapy or hormonal therapy (other than leuprolide or other GnRH agonists) within 30 days prior to the first dose of study drug and while on study treatment.
  • Patients receiving other anti-cancer non-drug therapies: radiation, or tumor embolization within 4 weeks prior to the first dose of study drug and while on study treatment.
  • Patient being treated with anti-vitamin K (AVK). Low molecular weight heparin (LMWH) is allowed.
  • Patient with uncontrolled infection
  • Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including uncontrolled diabetes,
  • Clinically relevant cardiovascular abnormalities, as judged by the investigator, such as, but not limited to, uncontrolled hypertension, congestive heart failure NYHA classification > III, unstable angina, myocardial infarction within six months prior to randomisation, or poorly controlled arrhythmia, chronic liver or renal disease, severely impaired lung function
  • Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g. Crohn's disease, malabsorption or CTCAE grade >1 diarrhea of any etiology at randomisation
  • Known pre-existing Interstitial Lung Disease (ILD)
  • Patients requiring comedication with potent P-gp inhibitors (including Cyclosporin, Erythromycin, Ketoconazole, Itraconazole, Quinidine, Phenobarbital salt with Quinidine, Ritonavir, Valspodar, Verapamil) or inducers (including St John's wort, rifampicin)
  • Patients with a known HIV, active hepatitis B and/or C infection
  • Pregnant women, women who are likely to be pregnant or are breast-feeding
  • Patients with 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
  • Patients who received any other investigational drugs within 30 days prior to the screening visit and/or during the study
  • Patients unwilling to participate in the biological investigations
  • Individually deprived of liberty or placed under the authority of a tutor
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01415674

Contacts
Contact: Christine Orsini +33.1.71.93.67.77 c-orsini@unicancer.fr

Locations
France
CHU d'Angers Recruiting
Angers, France
Principal Investigator: Laurent LACCOURREYE         
Institut de cancérologie de l'Ouest - Site Paul Papin Recruiting
Angers, France
Principal Investigator: Olivier CAPITAIN         
Centre François Baclesse Recruiting
Caen, France, 14000
Principal Investigator: Dominique De Raucourt         
Centre Léon Bérard Recruiting
Lyon, France, 69373
Principal Investigator: Jérôme Fayette         
Chu de Nantes Recruiting
Nantes, France
Principal Investigator: Olivier MALARD         
Institut de cancérologie de l'Ouest - Site René Gauducheau Recruiting
Nantes Saint-herblain, France
Principal Investigator: Frédéric ROLLAND         
Centre Antoine Lacassagne Recruiting
Nice, France, 06189
Principal Investigator: Frédéric PEYRADE         
Institut Curie Recruiting
Paris, France, 75248
Principal Investigator: Christophe Le Tourneau         
Institut Claudius Regaud Recruiting
Toulouse, France, 31052
Principal Investigator: Jean-Pierre Delord         
Centre Alexis Vautrin Recruiting
Vandoeuvre les Nancy, France, 54511
Principal Investigator: Gilles Dollivet         
Institut Gustave Roussy Recruiting
Villejuif, France, 94800
Principal Investigator: Stéphane TEMAM         
Sponsors and Collaborators
UNICANCER
Investigators
Principal Investigator: Christophe Le Tourneau Institut Curie, Paris
  More Information

No publications provided

Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT01415674     History of Changes
Other Study ID Numbers: GEP11/1010
Study First Received: August 10, 2011
Last Updated: September 2, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by UNICANCER:
Squamous cell carcinoma of the head and neck
pre operative treatment
Afatinib
BIBW2992
Biological markers

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell

ClinicalTrials.gov processed this record on November 24, 2014