Topical MTS-01 for Dermatitis During Radiation and Chemotherapy for Anal Cancer
Condition: Anal Cancer
MeSH terms: Anus Neoplasms; Dermatitis
Intervention: Tempol; 5-Fluorouracil; Mitomycin-C; Radiation Therapy
Intervention description: 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 radiation therapy (RT).; 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29.; Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29; Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Intervention MeSH terms: Fluorouracil; Mitomycins; Mitomycin; Tempol
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: Anal Cancer; Radioprotector; Topical; Radiation; Dermatitis

Summary:

      Background:

      - Radiation and chemotherapy treatments for anal cancer can cause irritation of the skin that
      can lead to redness and tenderness, and in some cases can be so severe that it results in
      blistering or peeling of the skin during treatment. These conditions cause discomfort and may
      require breaks from radiation treatment. Researchers are interested in determining whether
      MTS-01, a drug that protects cells and tissues from the effects of radiation, can be given
      before radiation treatment to prevent these side effects and reduce the irritation of the
      skin during chemotherapy and radiation for anal cancer.

      Objectives:

      - To determine the safety and effectiveness of topical MTS-01 given before radiation in the
      groin and gluteal cleft of patients receiving combined radiation and chemotherapy for anal
      cancer.

      Eligibility:

      - Individuals at least 18 years of age who have been diagnosed with cancer of the anal canal
      and are eligible to receive radiation and chemotherapy treatments.

      Design:

        -  Participants will be screened with a physical examination, medical history, blood tests,
           imaging studies and physical examination of the anal canal, and biopsies as needed to
           evaluate eligibility for treatment.

        -  Participants will be scheduled for radiation and chemotherapy treatments on the
           following schedule:

        -  Radiation given 5 days per week for 6 weeks, with topical MTS-01 treatment on the skin
           in the groin areas and between the buttocks before each treatment

        -  Mitomycin C given intravenously on days 1 and 29 of treatment

        -  5-Fluorouracil given intravenously over 4 days (first week and fifth week) during
           radiation treatment

        -  Participants will be monitored throughout the treatment for side effects, with
           photographs of the treatment area and frequent blood tests.

        -  Following the end of radiation, participants will have followup visits for 1 year with
           blood tests and imaging studies to evaluate the response to treatment.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Histologically proven, invasive primary squamous, basaloid, or cloacogenic carcinoma
             of the anal canal, stage T1-4, N0-3

          -  No previous therapy for anal cancer.

          -  Age greater than or equal to 18 years

          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2

          -  Adequate bone marrow, renal, and hepatic function defined as

               -  Absolute neutrophil count greater than or equal to 1,000 cells/mm(3)

               -  Platelet count greater than or equal to 100,000/mm(3)

               -  Hemoglobin greater than or equal to 8mg/dL

               -  Creatinine clearance > 60 mL/min using Cockcroft-Gault formula

               -  Bilirubin less than or equal to 1.5 times upper limit of normal (ULN) unless,
                  during screening, the patient is receiving protease inhibitor therapy (i.e.
                  indinavir, ritonavir, nelfinavir, and atazanavir) known to be associated with
                  increased bilirubin: in this case total bilirubin less than or equal to 7.5 mg/dl
                  and the direct fraction is less than or equal to 0.7 mg/dl.

               -  White blood cell (WBC) greater than or equal to 3,000/microL

               -  Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than or
                  equal to 3 times the upper limit of normal

               -  International normalized ratio (INR) less than or equal to 1.5

          -  Patients of childbearing potential must be willing to use a medically effective means
             of birth control for the duration of treatment and six weeks after treatment.

          -  Patients must be willing and able to provide informed consent

        EXCLUSION CRITERIA:

          -  Contraindications to radiotherapy such as a history of prior radiotherapy to the
             pelvis or a history of inflammatory bowel disease

          -  Prior malignancy except:

               -  non-melanoma skin cancer

               -  controlled Kaposi's Sarcoma (no chemotherapy for KS for 3 months, and no expected
                  need for chemotherapy for the 12-month period of the study)

               -  other malignancies with disease free period of at least 3 years

          -  Presence of metastatic disease (M1)

          -  Co-morbidity that in the estimation of the principal investigator would make the
             patient unable to tolerate treatment

          -  Pregnant or lactating females

          -  Human immunodeficiency virus (HIV) positive patients with cluster of differentiation 4
             (CD4) < 100 cells/mL AND ECOG performance status (PS) greater than 2.

          -  Dermatitis in the anticipated radiation treatment portal.