Precancerous Conditions
Conditions
Keywords
Skin Lesions, Premalignant Lesion
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.
Interventions
DRUGErlotinib & 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.
Sponsors
National Institutes of Health (NIH)
Emory University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | 12 months from time of enrollment | 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 | 12 months from time of enrollment | 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 | Up to 55 months from initiation of therapy. Median duration of follow-up was 36 months. | 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. |
Countries
United States
Participant flow
Recruitment details
Between October 24, 2006, and June 28, 2012, 36 subjects with documented premalignant lesions, including mild (mild-D), moderate, or severe oral leukoplakia, and carcinoma in situ (CIS) were screened. Lesion sites included oral cavity oropharynx, and the larynx.
Pre-assignment details
Seventeen subjects were enrolled on the study, 3 of whom withdrew consent (one male of 69 years of age, and two females of 43 and 42 years of age). Two patients who signed informed consent were deemed to be screen failures, one secondary to prior history of oral squamous cell carcinoma and the other secondary to a history of cardiac arrhythmias.
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib & Celecoxib 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. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Erlotinib & Celecoxib |
|---|---|
| Age, Customized 40-49 years old | 4 participants |
| Age, Customized 50-59 years old | 2 participants |
| Age, Customized 60-69 years old | 4 participants |
| Age, Customized 70-79 years old | 1 participants |
| Age, Customized 80-89 years old | 1 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 2 / 12 |
Outcome results
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.
Time frame: 12 months from time of enrollment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib & Celecoxib | Clinical Outcome: Documented Progression | Complete remission (CR) | 3 participants |
| Erlotinib & Celecoxib | Clinical Outcome: Documented Progression | Partial remission (PR) | 1 participants |
| Erlotinib & Celecoxib | Clinical Outcome: Documented Progression | Progressive disease (PD) | 1 participants |
| Erlotinib & Celecoxib | Clinical Outcome: Documented Progression | Stable disease (SDi) | 2 participants |
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.
Time frame: Up to 55 months from initiation of therapy. Median duration of follow-up was 36 months.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib & Celecoxib | Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma | Recurrent severe dysplasia | 1 participants |
| Erlotinib & Celecoxib | Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma | Stage I invasive carcinoma | 1 participants |
| Erlotinib & Celecoxib | Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma | Stage II oral cavity carcinoma | 1 participants |
| Erlotinib & Celecoxib | Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma | Invasive squamous cell carcinoma | 1 participants |
| Erlotinib & Celecoxib | Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma | Recurrent moderate dysplasia | 1 participants |
| Erlotinib & Celecoxib | Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma | Recurrent high-grade dysplasia | 1 participants |
| Erlotinib & Celecoxib | Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma | Complete remission | 1 participants |
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.
Time frame: 12 months from time of enrollment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Hypoalbuminemia, Grade 2 | 1 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Hypocalcemia, Grade 1 | 4 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Mouth sores, Grade 1 | 9 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Mouth sores, Grade 2 | 3 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Shortness of breath, Grade 1 | 3 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Strep throat, Grade 2 | 1 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Abdominal cramping, Grade 1 | 2 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Alopecia, Grade 1 | 2 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Anemia, Grade 1 | 2 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Anemia, Grade 2 | 1 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Anxiety, Grade 1 | 2 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Decreased protein, Grade 1 | 2 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Leukopenia, Grade 1 | 1 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Leukopenia, Grade 2 | 1 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Depression, Grade 1 | 3 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Diarrhea, Grade 1 | 5 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Dry eyes, Grade 1 | 4 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Dry skin, Grade 1 | 6 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Elevated LDH, Grade 1 | 3 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Elevated serum creatinine, Grade 1 | 4 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Elevated serum creatinine, Grade 2 | 1 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Elevated alkaline phosphatase, Grade 1 | 3 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Elevated ALT, Grade 1 | 5 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Elevated AST, Grade 4 | 4 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Fatigue, Grade 1 | 6 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Hyperbilirubinemia, Grade 1 | 2 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Hypercholesterolemia, Grade 1 | 2 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Hyperglycemia, Grade 1 | 7 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Hyperglycemia, Grade 2 | 2 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Hypoalbuminemia, Grade 1 | 3 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Hypoglycemia, Grade 1 | 1 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Hypoglycemia, Grade 2 | 1 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Hypokalemia, Grade 1 | 2 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Hyponatremia, Grade 1 | 3 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Mucositis, Grade 1 | 3 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Mucositis, Grade 3 | 1 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Nausea, Grade 1 | 4 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Neuropathy, Grade 1 | 3 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Pruritis, Grade 1 | 2 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Rash, Grade 1 | 8 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Rash, Grade 3 | 2 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Urosepsis, Grade 3 | 1 participants |
| Erlotinib & Celecoxib | Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4 | Vomiting, Grade 1 | 2 participants |