RTA 408 Lotion in Patients at Risk for Radiation Dermatitis - PRIMROSE
Condition: Breast Cancer
MeSH terms: Dermatitis; Radiodermatitis
Intervention: Omaveloxolone Lotion 0.5%; Omaveloxolone Lotion 3%; Vehicle Lotion; 3D conformal radiation therapy
Intervention description: Omaveloxolone lotion 0.5% will be applied topically twice-daily, for up to 13 weeks, during the course of radiation therapy; Omaveloxolone lotion 3% will be applied topically twice-daily, for up to 13 weeks, during the course of radiation therapy; Lotion vehicle manufactured to mimic RTA 408 lotion will be applied topically twice-daily, for up to 13 weeks, during the course of radiation therapy; 45 50.4 Gy in 1.8 Gy per day, in addition to 10 - 16 Gy boost or 46 - 50 Gy in 2 Gy per day, in addition to 10 - 16 Gy boost, at the physician's discretion
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 187.0
Sex: Female
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: RTA 408; RTA 408 Lotion; Breast cancer; Radiation therapy; Radiation dermatitis; Oxidative stress; Inflammation; omaveloxolone

Summary:

      Radiation dermatitis is experienced by almost all patients (up to 95%) receiving radiation
      therapy for cancer. Radiation dermatitis can be a serious condition because, in addition to
      its direct physical complications and the resulting impact on overall quality of life, it can
      also be a dose-limiting toxicity requiring changes to the prescribed course of radiation
      therapy. The most common strategy employed in an attempt to prevent or minimize radiation
      dermatitis involves moisturization of the irradiated area, use of a mild soap to keep the
      area clean, and minimizing exposure to potential mechanical irritants, such as scratching and
      rough clothing. However, this strategy has been shown to lack clinically significant
      efficacy. Consequently, there is a clinical need for new treatments that are effective in
      protecting against radiotherapy-induced oxidative stress and the subsequent development of
      radiation dermatitis.

      Based on data from previous studies in animals and humans, Reata believes that omaveloxolone
      (RTA 408) Lotion may effectively prevent and mitigate radiation dermatitis in oncology
      patients undergoing radiation therapy.

      This randomized, double-blind, vehicle-controlled, parallel-group trial will study the
      efficacy, tolerability and safety of two concentrations of omaveloxolone (RTA 408) Lotion (3%
      and 0.5%) versus vehicle in patients with breast cancer for whom radiation therapy is
      recommended.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adult female patients (18 to 75 years of age, inclusive);

          2. Patients diagnosed with ductal carcinoma in situ or non-inflammatory breast
             adenocarcinoma who have been referred for post-operative radiotherapy and have had no
             prior radiation treatment to that breast;

          3. Patients planning to undergo 3D conformal radiation therapy to the whole breast (as
             part of breast-conservation therapy / lumpectomy) or chest wall (as part of
             post-mastectomy irradiation), with or without treatment of regional lymph nodes (i.e.,
             axillary, supraclavicular, or internal mammary), using one of the following treatment
             schedules:

               1. 45 - 50.4 Gy in 1.8 Gy per day, in addition to 10-16 Gy boost

               2. 46 - 50 Gy in 2 Gy per day, in addition to 10-16 Gy boost;

          4. Patients who received breast-conservation therapy / lumpectomy must be receiving ≥
             107% of the total radiation dose (calculated from the total radiation dose including
             boost) to any portion of the breast, based on radiation inhomogeneity, and/or have a
             breast volume ≥ 1200 cc;

        Exclusion Criteria:

          1. Patients with Stage T4 or Stage IV breast cancer;

          2. Patients with prior radiation therapy to the breast treated in this study;

          3. Patients with type V or VI skin according to the Fitzpatrick scale;

          4. Patients with bilateral breast cancer;

          5. Patients receiving partial breast irradiation therapy;

          6. Patients with uncontrolled diabetes (HbA1c > 11.0%, historical values within 6 months
             of screening are acceptable);

          7. Patients with collagen vascular disease or vasculitis;

          8. Patients with concurrent active malignancy other than adequately treated basal cell
             carcinoma of the skin or carcinoma in situ of the cervix;

          9. Patients with active bacterial, fungal or viral skin infections;

         10. Patients with known active hepatitis B or hepatitis C infection;

         11. Patients who intend to use any other topical cream, lotion or preparation applied to
             the radiation treatment area;

         12. Patients receiving concomitant chemotherapy during the course of the planned radiation
             treatment regimen. Patients are eligible if they are receiving sequential, neoadjuvant
             or adjuvant chemotherapy that is not anticipated to be delivered during the time
             course of the radiation treatment regimen.