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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Erlotinib & Celecoxib

About this trial

This is an interventional diagnostic trial for Precancerous Conditions focused on measuring Skin Lesions, Premalignant Lesion

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Emory University Winship Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Erlotinib & Celecoxib

Arm Description

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT00314262

First Posted

April 11, 2006

Last Updated

October 21, 2014

Sponsor

Emory University

Collaborators

National Institutes of Health (NIH)

1. Study Identification

Unique Protocol Identification Number

NCT00314262

Brief Title

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

2. Study Status

Record Verification Date

October 2014

Overall Recruitment Status

Completed

Study Start Date

October 2006 (undefined)

Primary Completion Date

November 2012 (Actual)

Study Completion Date

November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Emory University

Collaborators

National Institutes of Health (NIH)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Precancerous Conditions

Keywords

Skin Lesions, Premalignant Lesion

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

17 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Erlotinib & Celecoxib

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Erlotinib & Celecoxib

Other Intervention Name(s)

OSI-774, Tarceva

Intervention Description

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.

Primary Outcome Measure Information:

Title

Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4

Description

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.

Time Frame

12 months from time of enrollment

Title

Clinical Outcome: Documented Progression

Description

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.

Time Frame

12 months from time of enrollment

Title

Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma

Description

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.

Time Frame

Up to 55 months from initiation of therapy. Median duration of follow-up was 36 months.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

No

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dong Shin, MD

Organizational Affiliation

Emory University Winship Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Emory University Winship Cancer Institute

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

23422093

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.

Results Reference

background

PubMed Identifier

24085777

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.

Results Reference

result

Precancerous Conditions

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial