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

NCT00314262 | Completed Phase 1 Results DMC

• 1 other identifier: IRB00024922
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Precancerous Conditions

Keywords

Skin Lesions; Premalignant Lesion

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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.

Study Arms (1)

Erlotinib & Celecoxib

EXPERIMENTAL

Drug: Erlotinib & Celecoxib

Interventions

Erlotinib & Celecoxib DRUG

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.

Also known as: OSI-774, Tarceva

Erlotinib & Celecoxib

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (2)

• 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.

  PMID: 23422093 BACKGROUND

• 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.

  PMID: 24085777 RESULT

MeSH Terms

Conditions

Precancerous Conditions

Interventions

Erlotinib Hydrochloride; Celecoxib

Condition Hierarchy (Ancestors)

Neoplasms

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

One limitation is the small number of patients who were evaluable for response.

Results Point of Contact

• Title: Dong Shin, MD
• Organization: Emory University School of Medicine

dmshin@emory.edu

404-778-2980

Study Officials

• Dong Shin, MD

  Emory University Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 11, 2006
• First Posted: April 13, 2006
• Study Start: October 1, 2006
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: October 24, 2014
• Results First Posted: October 24, 2014

Record last verified: 2014-10

Locations

US (1)