Trial Information

A Pilot Trial Assessing the Feasibility of Delivering Topical MTS-01 to Reduce Dermatitis in Patients Receiving Intensity Modulated Radiation With Concurrent 5-Fluorouracil and Mitomycin-C for Stage I-III Carcinoma of the Anal Canal

Background:

- Patients with non-metastatic carcinoma of the anal canal are treated with concurrent
mitomycin C (MMC), 5-fluorouracil (5-FU), and radiotherapy (RT) in the curative setting
in an attempt to preserve the anal sphincter.

- Radiation dermatitis is a uniform complication of this therapy which frequently results
in treatment delay due to pain and discomfort. High grade dermatitis may also become
superinfected in the setting of decreased blood counts from chemotherapy and diarrhea
from radiation proctitis, further delaying therapy. Approaches that decrease toxicity
may be particularly important in patients infected with HIV.

- MTS-01 (tempol, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is a piperidine
nitroxide known to act as a chemical radioprotector with selective protection of normal
versus tumor tissue.

- Tempol gel (tempol 70 mg/mL plus water, ethanol, and hydroxypropyl cellulose) has been
evaluated as a topical radioprotector in pilot trials that included a variety of sites.

Objectives:

- Primary Objective: To determine the safety and tolerability of topical MTS-01 on a
daily basis prior to irradiation in the groin and gluteal cleft of patients receiving
combined therapy with MMC, 5-FU, and RT for carcinoma of the anal canal.

- Secondary Objectives will include evaluation of the following endpoints in a
preliminary fashion:

- To describe the rates and severity of skin toxicity in patients treated with this
regimen

- To describe the need for toxicity related treatment breaks with this regimen

- To describe the opiate requirements in patients treated with this regimen

- To describe 12-month progression-free survival, disease-free survival, and overall
survival in patients treated with concurrent chemotherapy, radiation therapy, and
MTS-01

- Evaluate the effects of antiretroviral therapy, 5-fluorouracil, mitomycin C, and
radiation on low level persistent HIV viremia and HIV genetic diversity during
therapy and recovery

- To evaluate the feasibility of collecting HIV RNA and mononuclear cells from
rectal associated lymphoid tissue for correlative studies

- Collect and store anal cytology and core needle biopsies of tumor for future HPV
and tumor based analyses

Eligibility:

- Age greater than or equal to 18 years.

- ECOG performance status less than or equal to 2.

- Histologically confirmed carcinoma of the anal canal without evidence of distant
metastases

- No contraindications to definitive chemoradiotherapy for carcinoma of the anal canal

Design:

This is a pilot trial of topical MTS-01 in patients receiving MMC, 5-FU, and IMRT for
definitive management of carcinoma of the anal canal. Fifteen patients will be enrolled. MMC
will be delivered at a dose of 10mg/m(2) on days 1 and 29. 5-FU will be delivered as
1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. RT will be
delivered to a total dose of 50-54 Gy based on tumor characteristics. Tempol gel will be
applied to the bilateral groins and the gluteal cleft, avoiding a 3 cm radius from the anal
verge, immediately prior to each fraction of RT. RTOG grading will be used to evaluate skin
toxicity in both the groin and gluteal cleft weekly during treatment and at 4 weeks, 3
months and 6 months after completion of treatment. The duration of treatment, number of
treatment breaks, opiate requirements, and level of pain will be evaluated weekly during
treatment and at 4 weeks and 3 months after the completion of treatment. Disease control
will be assessed at 4 weeks, 3 months, 6 months, 9 months, and 12 months of follow-up.