Breast Cancer
Conditions
Keywords
RTA 408, RTA 408 Lotion, Breast cancer, Radiation therapy, Radiation dermatitis, Oxidative stress, Inflammation, omaveloxolone
Brief 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.
Interventions
DRUGOmaveloxolone Lotion 0.5%
Omaveloxolone lotion 0.5% will be applied topically twice-daily, for up to 13 weeks, during the course of radiation therapy
DRUGOmaveloxolone Lotion 3%
Omaveloxolone lotion 3% will be applied topically twice-daily, for up to 13 weeks, during the course of radiation therapy
DRUGVehicle 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
RADIATION3D 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
Sponsors
AbbVie
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Day 1 of radiation treatment through the last day of radiation treatment (maximum of 19 weeks), time averaged effect on radiation dermatitis reported | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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) | 64 |
| 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) | 62 |
| Vehicle Lotion Vehicle Lotion administered topically to the radiation area, twice daily for approximately 9 weeks (up to a maximum of 16 weeks) | 61 |
| Total | 187 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative Reasons | 1 | 0 | 1 |
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Missing | 0 | 1 | 0 |
| Overall Study | Patient didn't complete end of study visit | 0 | 0 | 1 |
| Overall Study | Treatment changed from radiation treatment to chemo | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 3 |
Baseline characteristics
| Characteristic | Omaveloxolone (RTA 408) Lotion 0.5% | Total | Vehicle Lotion | Omaveloxolone (RTA 408) Lotion 3% |
|---|---|---|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 8.8 | 56.8 years STANDARD_DEVIATION 9.8 | 56.6 years STANDARD_DEVIATION 10.3 | 56 years STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 11 Participants | 5 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 175 Participants | 56 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 24 Participants | 5 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 5 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 50 Participants | 155 Participants | 51 Participants | 54 Participants |
| Region of Enrollment United States | 64 participants | 187 participants | 61 participants | 62 participants |
| Sex: Female, Male Female | 64 Participants | 187 Participants | 61 Participants | 62 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 1 / 62 | 0 / 61 |
| other Total, other adverse events | 49 / 64 | 54 / 62 | 50 / 61 |
| serious Total, serious adverse events | 4 / 64 | 3 / 62 | 0 / 61 |
Outcome results
Primary
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
Time frame: Day 1 of radiation treatment through the last day of radiation treatment (maximum of 19 weeks), time averaged effect on radiation dermatitis reported
Population: Intent-to-treat population (all randomized patients whether or not they received study drug)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Omaveloxolone (RTA 408) Lotion 0.5% | 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 | 1.1 Grade |
| Omaveloxolone (RTA 408) Lotion 3% | 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 | 1.2 Grade |
| Vehicle Lotion | 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 | 1.2 Grade |
Comparison: Comparison of omaveloxolone lotion pooled (0.5% and 3%) versus vehicle lotionp-value: 0.23765% CI: [-0.2, 0]Mixed Models Analysis
Comparison: Comparison of Omaveloxolone Lotion 0.5% versus Vehicle Lotionp-value: >0.0595% CI: [-0.2, 0]Mixed Models Analysis
Comparison: Comparison of Omaveloxolone Lotion 3% versus Vehicle Lotionp-value: >0.0595% CI: [-0.1, 0.1]Mixed Models Analysis