Phase I/II Study of Chemoprevention With EGFR and COX-2 Inhibitor

Precancerous Conditions Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00314262
• Other study ID #: IRB00024922
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 11, 2006
• Last updated: October 21, 2014
• Start date: October 2006
• Est. completion date: November 2012

Study information

• Verified date: October 2014
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Precancerous Conditions

Intervention

Drug:
• Erlotinib & Celecoxib
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.

Locations

Country	Name	City	State
United States	Emory University Winship Cancer Institute	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Saba NF, Hurwitz SJ, Kono SA, Yang CS, Zhao Y, Chen Z, Sica G, Müller 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 hea — View Citation

Shin DM, Zhang H, Saba NF, Chen AY, Nannapaneni S, Amin AR, Müller 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4	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.	12 months from time of enrollment	Yes
Primary	Clinical Outcome: Documented Progression	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.	12 months from time of enrollment	No
Primary	Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma	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.	Up to 55 months from initiation of therapy. Median duration of follow-up was 36 months.	No