Clinical trial NCT00314262: Phase I/II Study of Chemoprevention With EGFR and COX-2 Inhibitor
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Precancerous Conditions
Keywords: Skin Lesions
Premalignant Lesion
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2006-04-13
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Evaluate effect on cells and patient response to study medications, assess side effects of these medications, and evaluate chemicals in cells that may tell how the drug works, before, and after receiving the study medications.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
timeFrame: 12 months from time of enrollment
measure: Clinical Outcome: Documented Progression
timeFrame: 12 months from time of enrollment
measure: Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma
timeFrame: Up to 55 months from initiation of therapy. Median duration of follow-up was 36 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
Study officials:
affiliation: Emory University Winship Cancer Institute
name: Dong Shin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.