Celecoxib in Preventing Skin Cancer in Patients With Actinic Keratoses

Study Overview
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Brief Summary
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RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of celecoxib may be an effective way to prevent actinic keratoses. PURPOSE: Randomized phase II/III trial to determine the effectiveness of celecoxib in preventing skin cancer in patients who have actinic keratoses.

Detailed Description
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OBJECTIVES: Compare celecoxib vs placebo in terms of preventing the development of new actinic keratoses in patients with actinic keratoses. Compare these treatment regimens in terms of inducing regression of actinic keratoses in these patients. Determine the safety of this drug in these patients. Compare the effect of these treatment regimens on potential surrogate end-point biomarkers in areas of actinic keratosis, sun-exposed skin, and non-sun-exposed skin and correlate these biomarkers with clinical outcome in these patients. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral celecoxib twice daily for 9 months in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive oral placebo as in arm I. Patients are followed at 2 months after completing treatment. PROJECTED ACCRUAL: A total of 240 patients (120 per treatment arm) will be accrued for this study.

Official Title
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A Phase II/III Randomized, Double-Blind, Placebo-Controlled Clinical Trial Of Celecoxib In Subjects With Actinic Keratoses

Conditions
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Precancerous Condition

Intervention / Treatment
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* Drug: celecoxib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of Fitzpatrick skin types I, II, or III Sun-damaged skin with 10-40 actinic keratoses on the upper extremities (upper arms, forearms, and hands), neck, face, and scalp combined PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Not specified Life expectancy: Not specified Hematopoietic: WBC at least 3,000/mm^3 Platelet count at least 125,000/mm^3 Hemoglobin at least lower limit of normal No significant bleeding disorder Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST and ALT no greater than 1.5 times ULN No chronic or acute hepatic disorder Renal: Creatinine no greater than 1.5 times ULN BUN no greater than 1.5 times ULN No chronic or acute renal disorder Gastrointestinal: No history of or active inflammatory bowel disease No active pancreatitis Not diagnosed with esophageal, gastric, pyloric channel, or duodenal ulceration within the past 30 days Other: No history of keloid formation No known photosensitivity disorder No history of hypersensitivity or adverse reaction to sulfonamides, COX-2 inhibitors, salicylates, or other NSAIDs No other condition that would preclude study No other medical or psychosocial condition that would preclude study No other malignancy within the past 5 years except: Carcinoma in situ of the cervix Curatively excised nonmelanoma skin cancer Stage 0 chronic lymphocytic leukemia Any cancer for which the patient is currently without evidence of disease, has not been treated for tumor within the past 6 months, has no current or planned therapy, and has an expected disease-free survival of at least 5 years Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: At least 30 days since prior systemic immunotherapy No concurrent immunotherapy Chemotherapy: At least 3 months since prior topical fluorouracil (5-FU) At least 6 months since other prior topical chemotherapy No concurrent topical chemotherapy, including 5-FU No other concurrent chemotherapy Endocrine therapy: At least 6 months since prior oral or IV corticosteroids for more than 2 consecutive weeks At least 6 months since prior inhaled or nasal corticosteroids for more than 4 weeks duration At least 14 days since prior topical corticosteroids At least 30 days since prior nasal corticosteroids (except mometasone) No concurrent oral or IV corticosteroids for more than 2 consecutive weeks during any 6 month period during study No concurrent inhaled or nasal steroids (except mometasone) for more than 4 weeks during any 6 month period during study No concurrent hormonal or steroidal therapy, including topical corticosteroids Concurrent hormone replacement therapy (e.g., estrogen or thyroid hormone replacement) allowed Radiotherapy: At least 6 months since prior local radiotherapy to areas being studied At least 30 days since other prior radiotherapy No concurrent radiotherapy, including local radiotherapy to areas being studied Surgery: Not specified Other: At least 30 days since prior cryotherapy to target lesions At least 60 days since prior laser resurfacing, dermabrasion, or chemical peels At least 30 days since prior investigational medication At least 14 days since prior topical alphahydroxyacids (e.g., glycolic acid or lactic acid) or retinoids At least 30 days since prior systemic psoralens or retinoids At least 30 days since prior treatment for esophageal, gastric, pyloric channel, or duodenal ulcers At least 30 days since prior aspirin (more than 100 mg/day), other nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors at a frequency of at least 3 times per week for more than 2 weeks (except cardioprotective doses of aspirin (no more than 100 mg/day) No concurrent systemic psoralens or retinoids No concurrent prescription or over-the-counter topical medications to areas being studied (e.g., vitamin A derivatives) No concurrent cryotherapy to target lesions No concurrent laser resurfacing, dermabrasion, or chemical peels No other concurrent investigational medications No concurrent fluconazole or lithium No concurrent chronic NSAIDs or COX-2 inhibitors (at least 3 times per week for more than 2 consecutive weeks per year) Concurrent cardioprotective doses of oral aspirin (100 mg per day or less) allowed Concurrent moisturizer/emollient or sunscreen allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 active arm<br>receipt of active drug | Drug: celecoxib<br> <br> |
| Experimental: Group 2 active arm<br>receipt of active drug | Drug: celecoxib<br> <br> |
| Experimental: group 2 placebo arm<br>receipt of placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare celecoxib vs placebo in terms of preventing the development of new actinic keratoses in patients with actinic keratoses. |  | baseline to 2 months after last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare these treatment regimens in terms of inducing regression of actinic keratoses in these patients. |  | baseline to 2 months after last dose | 
| Compare the effect of these treatment regimens on potential surrogate end-point biomarkers in areas of actinic keratosis, sun-exposed skin, and non-sun-exposed skin and correlate these biomarkers with clinical outcome in these patients. |  | baseline to 2 months after last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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actinic keratosis