- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00314262
Phase I/II Study of Chemoprevention With EGFR and COX-2 Inhibitor
Phase I/II Study of Chemoprevention With Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor Erlotinib (OSI-774, Tarceva) and Cyclooxygenase-2 (COX-2) Inhibitor (Celecoxib) in Premalignant Lesions of Head and Neck of Former Smokers
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
The purpose of this study is to evaluate the effect on cells and patient response to study medications, assess the side effects of these medications, and to evaluate chemicals in the cells that may tell how the drug works, before, and after receiving the study medications.
Approximately 61 patients will participate at Emory Winship Cancer Institute and Emory Crawford W. Long Hospital in Atlanta, Georgia.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
- La phase 1
Contacts et emplacements
Lieux d'étude
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Georgia
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Atlanta, Georgia, États-Unis, 30322
- Emory University Winship Cancer Institute
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Participants must have premalignant lesions.
- Lesion sites include oral cavity, oropharynx, and larynx.
- Must have at least a >20 pack-year history of smoking.
- Must have a Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0-1.
- Participants must be 18 years of age or older.
- No contraindications for laryngoscopy and biopsy.
- Adequate liver function.
- Must have hemoglobin and hematocrit levels at or above the lower limit of the normal range.
- Participants must have prothrombin time (PT)/partial thromboplastin time (PTT) levels at or above the lower limit of the normal range.
- Women of child-bearing potential must have a negative serum pregnancy test within 72 hours of receiving treatment.
- Must be able to swallow the oral dose of erlotinib and celecoxib.
- Participants must be disease free.
- Final eligibility will be determined by the health professionals conducting the trial.
Exclusion Criteria:
- Participants with acute intercurrent illness or those who had surgery within the preceding 4 weeks unless they have fully recovered.
- History of previous malignancies unless the cancer was stage I or II and rendered free of disease more than 1 year.
- Pregnant or breast feeding.
- Not practicing adequate contraception if the participants are of child bearing potential.
- Female patients who have a positive pregnancy test.
- History or recent myocardial infarction.
- Hypertension not adequately controlled by medication.
- Documented history of coagulopathy.
- Documented history of congestive heart failure (CHF) greater than New York Heart Association (NYHA) Grade II.
- Participants who were taking COX-2 inhibitors or EGFR tyrosine kinase inhibitors within 3 months of study entry.
- Documented history or interstitial lung disease.
- Known connective tissue disease.
- History of nonsteroidal antiinflammatory drug (NSAID)-induced ulcers or those who are at risk for a GI ulcer.
- Participated in a clinical trial of an investigational drug within 12 months prior to enrollment.
- Final eligibility will be determined by the health professionals conducting the trial.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Diagnostique
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: Erlotinib & Celecoxib
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Erlotinib given orally, once daily (dose escalation from 50 mg, 75 mg, or 100 mg) continuously for 6 months in the phase I portion. Celecoxib given 400 mg orally BID continuously for 6 months.
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Délai: 12 months from time of enrollment
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Participants received a fixed dose of celecoxib 400 mg orally BID continuously for 6 months.
Erlotinib was dose escalated at 3 dose levels of 50, 75, and 100 mg orally every day for 6 months.
Dose escalation followed a standard 3+3 escalation design.
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12 months from time of enrollment
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Clinical Outcome: Documented Progression
Délai: 12 months from time of enrollment
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Response evaluation was based on pathologic examination of the degree of dysplasia observed and recorded by an expert head and neck pathologist.
Pathologic complete response was defined as complete disappearance of dysplasia from the epithelium.
Pathologic partial response was defined as improvement of dysplasia by at least one degree (i.e., severe dysplasia becomes moderate dysplasia).
Pathologic minor response or stable disease was defined as minor focal improvement without change of degree of dysplasia (i.e., focal improvement from moderate to mild dysplasia with still moderate dysplasia overall) or no pathologic changes after treatment.
Pathologic progressive disease was defined as worsening by at least one degree of dysplasia (i.e., mild to moderate dysplasia) or development of invasive cancer on or following treatment.
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12 months from time of enrollment
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Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma
Délai: Up to 55 months from initiation of therapy. Median duration of follow-up was 36 months.
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Response evaluation was based on pathologic examination of the degree of dysplasia observed and recorded by an expert head and neck pathologist.
Pathologic complete response was defined as complete disappearance of dysplasia from the epithelium.
Pathologic partial response was defined as improvement of dysplasia by at least one degree (i.e., severe dysplasia becomes moderate dysplasia).
Pathologic minor response or stable disease was defined as minor focal improvement without change of degree of dysplasia (i.e., focal improvement from moderate to mild dysplasia with still moderate dysplasia overall) or no pathologic changes after treatment.
Pathologic progressive disease was defined as worsening by at least one degree of dysplasia (i.e., mild to moderate dysplasia) or development of invasive cancer on or following treatment.
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Up to 55 months from initiation of therapy. Median duration of follow-up was 36 months.
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Dong Shin, MD, Emory University Winship Cancer Institute
Publications et liens utiles
Publications générales
- Shin DM, Zhang H, Saba NF, Chen AY, Nannapaneni S, Amin AR, Muller S, Lewis M, Sica G, Kono S, Brandes JC, Grist WJ, Moreno-Williams R, Beitler JJ, Thomas SM, Chen Z, Shin HJ, Grandis JR, Khuri FR, Chen ZG. Chemoprevention of head and neck cancer by simultaneous blocking of epidermal growth factor receptor and cyclooxygenase-2 signaling pathways: preclinical and clinical studies. Clin Cancer Res. 2013 Mar 1;19(5):1244-56. doi: 10.1158/1078-0432.CCR-12-3149. Epub 2013 Feb 19.
- Saba NF, Hurwitz SJ, Kono SA, Yang CS, Zhao Y, Chen Z, Sica G, Muller S, Moreno-Williams R, Lewis M, Grist W, Chen AY, Moore CE, Owonikoko TK, Ramalingam S, Beitler JJ, Nannapaneni S, Shin HJ, Grandis JR, Khuri FR, Chen ZG, Shin DM. Chemoprevention of head and neck cancer with celecoxib and erlotinib: results of a phase ib and pharmacokinetic study. Cancer Prev Res (Phila). 2014 Mar;7(3):283-91. doi: 10.1158/1940-6207.CAPR-13-0215. Epub 2013 Oct 3.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Tumeurs
- Conditions précancéreuses
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents du système nerveux périphérique
- Inhibiteurs d'enzymes
- Analgésiques
- Agents du système sensoriel
- Agents anti-inflammatoires non stéroïdiens
- Analgésiques, non narcotiques
- Agents anti-inflammatoires
- Agents antirhumatismaux
- Inhibiteurs de la cyclooxygénase
- Agents antinéoplasiques
- Inhibiteurs de protéine kinase
- Inhibiteurs de la cyclooxygénase 2
- Chlorhydrate d'erlotinib
- Célécoxib
Autres numéros d'identification d'étude
- IRB00024922
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