Trial Outcomes & Findings for Phase I/II Study of Chemoprevention With EGFR and COX-2 Inhibitor (NCT NCT00314262)
NCT ID: NCT00314262
Last Updated: 2014-10-24
Results Overview
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.
COMPLETED
PHASE1/PHASE2
17 participants
12 months from time of enrollment
2014-10-24
Participant Flow
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.
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.
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
7
|
|
Overall Study
NOT COMPLETED
|
5
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Overall Study
Adverse Event
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
Phase I/II Study of Chemoprevention With EGFR and COX-2 Inhibitor
Baseline characteristics by cohort
| Measure |
Erlotinib & Celecoxib
n=12 Participants
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.
|
|---|---|
|
Age, Customized
40-49 years old
|
4 participants
n=5 Participants
|
|
Age, Customized
50-59 years old
|
2 participants
n=5 Participants
|
|
Age, Customized
60-69 years old
|
4 participants
n=5 Participants
|
|
Age, Customized
70-79 years old
|
1 participants
n=5 Participants
|
|
Age, Customized
80-89 years old
|
1 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 months from time of enrollmentParticipants 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.
Outcome measures
| Measure |
Erlotinib & Celecoxib
n=7 Participants
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.
|
|---|---|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Fatigue, Grade 1
|
6 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Hyperbilirubinemia, Grade 1
|
2 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Strep throat, Grade 2
|
1 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Abdominal cramping, Grade 1
|
2 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Alopecia, Grade 1
|
2 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Anemia, Grade 1
|
2 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Anemia, Grade 2
|
1 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Anxiety, Grade 1
|
2 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Decreased protein, Grade 1
|
2 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Leukopenia, Grade 1
|
1 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Leukopenia, Grade 2
|
1 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Depression, Grade 1
|
3 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Diarrhea, Grade 1
|
5 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Dry eyes, Grade 1
|
4 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Dry skin, Grade 1
|
6 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Elevated LDH, Grade 1
|
3 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Elevated serum creatinine, Grade 1
|
4 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Elevated serum creatinine, Grade 2
|
1 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Elevated alkaline phosphatase, Grade 1
|
3 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Elevated ALT, Grade 1
|
5 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Elevated AST, Grade 4
|
4 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Hypercholesterolemia, Grade 1
|
2 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Hyperglycemia, Grade 1
|
7 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Hyperglycemia, Grade 2
|
2 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Hypoalbuminemia, Grade 1
|
3 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Hypoalbuminemia, Grade 2
|
1 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Hypocalcemia, Grade 1
|
4 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Hypoglycemia, Grade 1
|
1 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Hypoglycemia, Grade 2
|
1 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Hypokalemia, Grade 1
|
2 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Hyponatremia, Grade 1
|
3 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Mouth sores, Grade 1
|
9 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Mouth sores, Grade 2
|
3 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Mucositis, Grade 1
|
3 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Mucositis, Grade 3
|
1 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Nausea, Grade 1
|
4 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Neuropathy, Grade 1
|
3 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Pruritis, Grade 1
|
2 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Rash, Grade 1
|
8 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Rash, Grade 3
|
2 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Shortness of breath, Grade 1
|
3 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Urosepsis, Grade 3
|
1 participants
|
|
Dose Escalation and Toxicity: Toxicities Including Grades 1 to 4
Vomiting, Grade 1
|
2 participants
|
PRIMARY outcome
Timeframe: 12 months from time of enrollmentResponse 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.
Outcome measures
| Measure |
Erlotinib & Celecoxib
n=7 Participants
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.
|
|---|---|
|
Clinical Outcome: Documented Progression
Complete remission (CR)
|
3 participants
|
|
Clinical Outcome: Documented Progression
Partial remission (PR)
|
1 participants
|
|
Clinical Outcome: Documented Progression
Progressive disease (PD)
|
1 participants
|
|
Clinical Outcome: Documented Progression
Stable disease (SDi)
|
2 participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Erlotinib & Celecoxib
n=7 Participants
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.
|
|---|---|
|
Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma
Stage I invasive carcinoma
|
1 participants
|
|
Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma
Stage II oral cavity carcinoma
|
1 participants
|
|
Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma
Invasive squamous cell carcinoma
|
1 participants
|
|
Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma
Recurrent moderate dysplasia
|
1 participants
|
|
Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma
Recurrent severe dysplasia
|
1 participants
|
|
Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma
Recurrent high-grade dysplasia
|
1 participants
|
|
Clinical Outcome: Progression to a Higher-grade Dysplasia or Carcinoma
Complete remission
|
1 participants
|
Adverse Events
Erlotinib & Celecoxib
Serious adverse events
| Measure |
Erlotinib & Celecoxib
n=12 participants at risk
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.
|
|---|---|
|
Skin and subcutaneous tissue disorders
Rash (Grade 3)
|
8.3%
1/12
|
|
Gastrointestinal disorders
Mucositis (Grade 3)
|
8.3%
1/12
|
|
Infections and infestations
Urosepsis (Grade 3)
|
8.3%
1/12
|
Other adverse events
| Measure |
Erlotinib & Celecoxib
n=12 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Abdominal cramping (Grade 1)
|
16.7%
2/12
|
|
Renal and urinary disorders
Alopecia (Grade 1)
|
16.7%
2/12
|
|
Blood and lymphatic system disorders
Anemia (Grade 1)
|
16.7%
2/12
|
|
Blood and lymphatic system disorders
Anemia (Grade 2)
|
8.3%
1/12
|
|
Psychiatric disorders
Anxiety (Grade 1)
|
16.7%
2/12
|
|
Blood and lymphatic system disorders
Decreased protein (Grade 1)
|
16.7%
2/12
|
|
Immune system disorders
Leukopenia (Grade 1)
|
8.3%
1/12
|
|
Immune system disorders
Leukopenia (Grade 2)
|
8.3%
1/12
|
|
Psychiatric disorders
Depression (Grade 1)
|
25.0%
3/12
|
|
Gastrointestinal disorders
Diarrhea (Grade 1)
|
41.7%
5/12
|
|
Eye disorders
Dry Eyes (Grade 1)
|
33.3%
4/12
|
|
Skin and subcutaneous tissue disorders
Dry Skin (Grade 1)
|
50.0%
6/12
|
|
Blood and lymphatic system disorders
Elevated Lactate Dehydrogenase (Grade 1)
|
25.0%
3/12
|
|
Renal and urinary disorders
Elevated Serum Creatinine (Grade 1)
|
33.3%
4/12
|
|
Blood and lymphatic system disorders
Elevated Alkaline Phosphatase (Grade 1)
|
25.0%
3/12
|
|
Blood and lymphatic system disorders
Elevated Alanine Aminotransferase (Grade 1)
|
41.7%
5/12
|
|
Blood and lymphatic system disorders
Elevated Aspartate Aminotransferase (Grade 1)
|
33.3%
4/12
|
|
General disorders
Fatigue (Grade 1)
|
50.0%
6/12
|
|
Blood and lymphatic system disorders
Hyperbilirubinemia (Grade 1)
|
16.7%
2/12
|
|
Blood and lymphatic system disorders
Hypercholesterolemia (Grade 2)
|
16.7%
2/12
|
|
Blood and lymphatic system disorders
Hyperglycemia (Grade 1)
|
58.3%
7/12
|
|
Blood and lymphatic system disorders
Hyperglycemia (Grade 2)
|
16.7%
2/12
|
|
Blood and lymphatic system disorders
Hypoalbuminemia (Grade 1)
|
25.0%
3/12
|
|
Blood and lymphatic system disorders
Hypoalbuminemia (Grade 2)
|
8.3%
1/12
|
|
Blood and lymphatic system disorders
Hypocalcemia (Grade 1)
|
33.3%
4/12
|
|
Blood and lymphatic system disorders
Hypoglycemia (Grade 1)
|
8.3%
1/12
|
|
Blood and lymphatic system disorders
Hypoglycemia (Grade 2)
|
8.3%
1/12
|
|
Blood and lymphatic system disorders
Hypokalemia (Grade 1)
|
16.7%
2/12
|
|
Blood and lymphatic system disorders
Hyponatremia (Grade 1)
|
25.0%
3/12
|
|
Skin and subcutaneous tissue disorders
Mouth Sores (Grade 1)
|
75.0%
9/12
|
|
Skin and subcutaneous tissue disorders
Mouth Sores (Grade 2)
|
25.0%
3/12
|
|
Gastrointestinal disorders
Mucositis (Grade 1)
|
25.0%
3/12
|
|
General disorders
Nausea (Grade 1)
|
33.3%
4/12
|
|
Nervous system disorders
Neuropathy (Grade 1)
|
25.0%
3/12
|
|
Skin and subcutaneous tissue disorders
Pruritis (Grade 1)
|
16.7%
2/12
|
|
Skin and subcutaneous tissue disorders
Rash (Grade 1)
|
66.7%
8/12
|
|
General disorders
Shortness of Breath (Grade 1)
|
25.0%
3/12
|
|
Infections and infestations
Strep Throat (Grade 2)
|
8.3%
1/12
|
|
Gastrointestinal disorders
Vomiting (Grade 1)
|
16.7%
2/12
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place