RTA 408 Lotion in Patients at Risk for Radiation Dermatitis - PRIMROSE

A Randomized, Double-blind, Vehicle-controlled, Parallel-group Phase 2 Study of the Efficacy, Safety, and Pharmacokinetics of RTA 408 Lotion in the Treatment of Patients at Risk for Radiation Dermatitis

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.

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.