T4N5 Liposomal Lotion in Preventing The Recurrence of Nonmelanoma Skin Cancer in Patients Who Have Undergone a Kidney Transplant

PRIMARY OBJECTIVES:

I. Compare the incidence of nonmelanoma skin cancer (NMSC) (average per patient) on the
sun-exposed skin of renal transplant recipients with a history of NMSC treated with T4N5
liposomal lotion vs placebo.

SECONDARY OBJECTIVES:

I. Compare the proportion of these patients who develop NMSC on sun-exposed skin during
treatment and after cessation of treatment with these regimens.

II. Compare the incidence of NMSC on the sun-exposed skin of these patients after cessation
of treatment with these regimens.

III. Compare the incidence of recurrent and de novo actinic keratoses (AKs) in patients
treated with these regimens.

IV. Determine whether either of these regimens induces regression of AKs left untreated on
the sun-exposed skin of these patients.

V. Compare the proportion of these patients who develop melanoma, in both treated and
untreated sites, during and after cessation of treatment with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to study center. Patients are randomized to 1 of 2 arms.

Six months before randomization, lesions suspicious for nonmelanoma skin cancer (NMSC) are
surgically removed and histologically analyzed. All but 10 randomly selected non-suspicious
lesions are removed. Of these 10 lesions, 5 are shave biopsied immediately pre-treatment for
histologic and surrogate endpoint biomarker (SEB) analysis and to determine a baseline
actinic keratosis: wart ratio. Patients also undergo a pre-treatment biopsy of normal
appearing sun-exposed and non-sun-exposed skin (buttocks).

Arm I: Patients apply T4N5 liposomal lotion topically to non-occluded, sun-exposed areas of
the head, neck, face, and upper extremities once daily for 12 months.

Arm II: Patients apply placebo topically to non-occluded, sun-exposed areas of the head,
neck, face, and upper extremities once daily for 12 months.

Treatment in both arms continues in the absence of the development of metastatic cutaneous
squamous cell cancer or melanoma. Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this
study within 6 months.

Inclusion Criteria:

- History of histologically confirmed nonmelanoma skin cancer

- Renal transplant recipient ≥ 4 years ago

- Currently receiving standard multi-agent pharmacologic immunosuppression

- Fitzpatrick skin type I, II, or III

- Sun-damaged skin with ≥ 10 lesions consistent with actinic keratoses OR wart on the
upper extremities (arms, forearms, hands), neck, face, and exposed scalp combined

- No history of keloid formation

- No known photosensitivity disorder

- No history of malignant melanoma

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No diagnosis of acute allograft rejection within the past 30 days requiring an
increase in immunosuppression

- No invasive malignancy within the past 4 years except curatively excised NMSC, cured
polyclonal posttransplantation lymphoproliferative disease, carcinoma in situ of the
cervix, stage 0 chronic lymphocytic leukemia, unless all of the following criteria
are met:

- No current evidence of disease

- No treatment for the invasive malignancy within the past 6 months

- No concurrent or planned therapy for the invasive malignancy

- Has an expected disease-free survival of at least 5 years

- No diagnosis of melanoma or melanoma in situ

- No other medical or psychosocial condition that would preclude study participation

- No likelihood, in the opinion of the transplant surgeon/nephrologist, to experience
graft loss and/or discontinue standard immunosuppressive therapy during study
treatment

- More than 30 days since prior and no concurrent topical chemotherapy (including
topical fluorouracil) to areas being studied

- No concurrent topical preparations containing corticosteroids

- More than 30 days since prior and no concurrent local radiotherapy to a study area

- More than 30 days since prior and no concurrent cryotherapy to target lesions

- No prior or concurrent experimental immunosuppressive agents

- More than 30 days since prior investigational medication

- More than 30 days since prior and no concurrent systemic psoralens or retinoids

- More than 60 days since prior and no concurrent laser resurfacing, dermabrasion, or
chemical peels to a study area

- No other concurrent investigational agents

- No other concurrent topical medications, including prescription and over the counter
preparations, to the areas being studied (e.g., upper arms, forearms, neck, face, and
scalp)

- Concurrent moisturizer, emollient, and sunscreen allowed

- No concurrent topical preparations containing vitamin A derivatives

- No concurrent nonsteroidal anti-inflammatory drugs

- Concurrent cardioprotective doses of aspirin (< 100 mg/day) allowed