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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Omaveloxolone Lotion 0.5%; Radiation: 3D conformal radiation therapy; Drug: Omaveloxolone Lotion 3%; Drug: Vehicle Lotion

Detailed Description

Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.

• Study Type: Interventional
• Enrollment (Actual): 187
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Ironwood Cancer and Research Centers
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center
    • Scottsdale, Arizona, United States, 85258
      • Arizona Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital, Dept. of Radiation Oncology
  • Connecticut
    • Norwalk, Connecticut, United States, 06856
      • Norwalk Hospital
  • Florida
    • Lakeland, Florida, United States, 33805
      • Lakeland Regional Cancer Center
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B. Amos Cancer Center
  • Indiana
    • Anderson, Indiana, United States, 46016
      • St. Vincent Anderson Regional Hospital Cancer Center
    • Fort Wayne, Indiana, United States, 46845
      • Parkview Research Center
    • Fort Wayne, Indiana, United States, 46845
      • Radiation Oncology Associates - Parkview Research Center
    • South Bend, Indiana, United States, 46628
      • Northern Indiana Cancer Research Consortium
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Willis-Knighton Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center - Eppley Cancer Center
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • CaroMont Health Comprehensive Cancer Center
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Health
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • St. John Health System
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • East Stroudsburg, Pennsylvania, United States, 18301
      • Hughes Cancer Center
    • State College, Pennsylvania, United States, 16803
      • Mount Nittany Medical Center
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Cancer Center
    • Myrtle Beach, South Carolina, United States, 29577
      • 21st Century Oncology - Carolina Regional Cancer Center
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Regional Medical Center - Gibbs Cancer Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Research/USD
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
  • Washington
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Mayo Clinic - LaCrosse
    • Milwaukee, Wisconsin, United States, 53211
      • Columbia St. Mary's

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: omaveloxolone (RTA 408) Lotion 0.5%; Omaveloxolone Lotion at a fixed dose of 0.5% administered topically to the radiation area, twice daily for approximately 9 weeks (up to a maximum of 16 weeks)	Drug: Omaveloxolone Lotion 0.5%; Omaveloxolone lotion 0.5% will be applied topically twice-daily, for up to 13 weeks, during the course of radiation therapy; Other Names: RTA 408 Lotion 0.5%; Radiation: 3D conformal 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
Experimental: omaveloxolone (RTA 408) Lotion 3%; Omaveloxolone Lotion at a fixed dose of 3% administered topically to the radiation area, twice daily for approximately 9 weeks (up to a maximum of 19 weeks)	Radiation: 3D conformal 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; Drug: Omaveloxolone Lotion 3%; Omaveloxolone lotion 3% will be applied topically twice-daily, for up to 13 weeks, during the course of radiation therapy; Other Names: RTA 408 Lotion 3%
Placebo Comparator: Vehicle Lotion; Vehicle Lotion administered topically to the radiation area, twice daily for approximately 9 weeks (up to a maximum of 16 weeks)	Radiation: 3D conformal 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; Drug: Vehicle Lotion; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-averaged Effect on Radiation Dermatitis Grade Measured With Common Terminology Criteria for Adverse Events (CTCAE, v 4.03) Following 3D Conformal Radiation Therapy to the Breast Following Topical Application of Omaveloxolone Lotion or Lotion Vehicle	CTCAE Radiation dermatitis scoring: Grade 0 = No radiation dermatitis; Grade 1 = Faint erythema or dry desquamation; Grade 2 = Moderate to brisk erythema, patchy moist desquamation, mostly confined to skin folds and creases, moderate edema; Grade 3 = Moist desquamation in areas other than skin folds and creases, bleeding induced by minor trauma or abrasion; Grade 4 = Life-threatening consequences, skin necrosis or ulceration of full thickness dermis, spontaneous bleeding from involved site, skin graft indicated; Grade 5 = Death	Day 1 of radiation treatment through the last day of radiation treatment (maximum of 19 weeks), time averaged effect on radiation dermatitis reported

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Count of patients who experience a maximum radiation dermatitis grade of less than 2	Count the number of patients who experience a maximum radiation dermatitis grade of less than 2 (based on CTCAE grading scale) due to treatment with radiation therapy, following topical application of RTA 408 lotion or lotion vehicle	9 weeks (maximum of 13 weeks)
Grading of radiation dermatitis following radiation therapy	Calculate the mean maximum radiation dermatitis grade measured with CTCAE of RTA 408 Lotion (0.5% and 3%) compared with lotion vehicle.	9 weeks (max of 13 weeks)
Grading the duration of radiation dermatitis following radiation therapy	Calculate the mean duration of grade greater than or equal to 2 radiation dermatitis using the CTCAE criteria following administration of RTA 408 Lotion compared with lotion vehicle.	9 weeks (max of 13 weeks)

Collaborators and Investigators

• Sponsor: Reata, a wholly owned subsidiary of Biogen
• Collaborators: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2014
• Primary Completion (Actual): April 30, 2015
• Study Completion (Actual): April 30, 2015

Study Registration Dates

• First Submitted: May 16, 2014
• First Submitted That Met QC Criteria: May 16, 2014
• First Posted (Estimated): May 20, 2014

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Oxidative stress; Inflammation; Breast cancer; Radiation therapy; RTA 408; omaveloxolone; Radiation dermatitis; RTA 408 Lotion
• Additional Relevant MeSH Terms: Skin Diseases; Wounds and Injuries; Radiation Injuries; Dermatitis; Radiodermatitis
• Other Study ID Numbers: RTA 408-C-1306

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/