Breast Carcinoma, Pain, Radiation-Induced Dermatitis, Stage 0 Breast Cancer
Conditions
Brief summary
This randomized pilot phase II trial studies and compares prophylactic topical agents in reducing radiation-induced dermatitis in patients with non-inflammatory breast cancer or breast cancer in situ. The prophylactic topical agents, such as curcumin-based gel or HPR Plus, may reduce the severity of the radiation-induced dermatitis by minimizing water loss and inflammation during radiation therapy.
Detailed description
PRIMARY OBJECTIVE: I. To investigate the effectiveness of Curcumin gel (curcumin-based gel) or HPR Plus™ in reducing radiation dermatitis in breast cancer patients.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGCurcumin-based Gel
Applied topically
PROCEDUREDermatologic Complications Management
Apply HPR Plus topically
OTHERPlacebo
Apply placebo gel topically
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Gary Morrow
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with a diagnosis of non-inflammatory breast cancer or carcinoma in situ * Subjects must be prescribed and scheduled for conventional fractionated RT without concurrent chemotherapy; bolus and intensity modulated radiation therapy (IMRT) are permitted; lymph node irradiation (i.e., internal mammary nodes, supraclavicular nodes, axillary nodes, etc) as part of their prescribed radiation therapy are permitted; conventional fractionated radiation therapy regimens eligible for study are described below: * Minimal (min) total dose: whole breast: 44 gray (Gy); breast boost: 10 Gy; tumor bed = whole breast +/- boost: 50.0 Gy; lymph nodes: 45 Gy * Maximal (max) total dose: whole breast: 50.4 Gy; breast boost: 20 Gy; tumor bed = whole breast +/- boost: 66.0 Gy; lymph nodes: 50.4 Gy * Min dose per fraction: whole breast: 1.8 Gy; breast boost: 2.0 Gy; tumor bed = whole breast +/- boost: 1.8 Gy; lymph nodes: 1.8 Gy * Max dose per fraction: whole breast: 2.0 Gy; breast boost: 2.0 Gy; tumor bed = whole breast +/- boost: 2.0 Gy; lymph nodes: 2.0 Gy * Min # of fractions: whole breast: 22 Gy; breast boost: 5 Gy; tumor bed = whole breast +/- boost: 25 Gy; lymph nodes: 25 Gy * Max # of fractions: whole breast: 28 Gy; breast boost: 10 Gy; tumor bed = whole breast +/- boost: 36 Gy; lymph nodes: 28 Gy * Min # of sessions: whole breast: 22 Gy; breast boost: 5 Gy; tumor bed = whole breast +/- boost: 25 Gy; lymph nodes: 25 Gy * Max # of sessions: whole breast: 28 Gy; breast boost: 10 Gy; tumor bed = whole breast +/- boost: 36 Gy; lymph nodes: 28 Gy * Subjects may or may not have had surgery (lumpectomy or mastectomy) prior to RT; (NOTE: surgery is not required for eligibility) * Subjects may have had chemotherapy prior to radiation; a minimum of two weeks is required between end of chemotherapy and start of RT * Subjects may be currently prescribed hormone treatment or Herceptin therapy * Subjects must be able to read, speak, and understand English * Subjects must have the ability to understand and the willingness to sign a written informed consent document * Subjects must agree to not use any other topical agents on skin in the radiation treatment area during the course of this trial; subjects should only use topical agents for the study (i.e., topical intervention or standard care agents) supplied by the study personnel and/or treating physician
Exclusion criteria
* Pregnant females are ineligible; all subjects of childbearing potential will be asked if they are pregnant or could be pregnant; the patient must respond no to continue with radiation and to participate in this clinical study * Subjects with bilateral breast cancer are not eligible * Subjects receiving the short-course fractionation radiation therapy (i.e., 16 sessions or 20 sessions at 2.4 to 2.6 Gy fractions per session, with or without boost) * Subject is currently on anti-EGFR (human epidermal growth factor receptor) therapy, such as Iressa (gefitinib) or Erbitux (cetuximab, C225) * Previous radiation to the chest or breast * Subjects with breast reconstruction prior to RT * Previous diagnosis of radiosensitivity disorder (i.e., ataxia telangiectasia) * Previous diagnosis of collagen vascular disorder or vasculitis * Presence of unhealed surgical wounds in chest or breast region and/or breast infection * Current daily application of a prescribed topical product to the skin within the RT area for an unrelated skin condition that cannot be discontinued during the participation in this clinical trial * Presence of any active dermatological issues in radiation treatment area (i.e., fungal skin infection, dermatitis, psoriasis plaques, etc)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Radiation Dermatitis Severity (RDS) Score. Range: 0 (no Dermatitis) - 4 (Violaceous Erythema With Diffuse Desquamation Occurring in Sheets; Patchy Crusting; Superficial Ulceration) | Baseline up to 1 week post radiation therapy | The mean 1 week post-RT RDS score for each arm will be compared using ANOVA to determine if the topical interventions reduce the severity of skin reactions at the end of RT. The RDS score ranges from 0-4 with higher scores indicating worse outcome. |
| Incidence of Moist Desquamation (Present vs. Absent) | Baseline up to completion of radiation therapy | The degree to which each topical intervention decreases the incidence of moist desquamation will be examined using Fisher's exact test. Each agent's potential as a preventative intervention will be determined through comparison of the proportion of subjects with no to minimal radiation dermatitis within each arm using Fisher's exact test. |
| Change in the Severity of Skin Reactions Using the Radiation Dermatitis Scale (RDS). Range: 0 (no Dermatitis) - 4 (Violaceous Erythema With Diffuse Desquamation Occurring in Sheets; Patchy Crusting; Superficial Ulceration) | Baseline to up to 1 week after completion of radiation therapy | The mean 1 week post-RT RDS score for each arm will be compared using ANOVA to determine if the topical interventions reduce the severity of skin reactions after completion of RT. The RDS score ranges from 0-4 with higher scores indicating worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Curcumin-based Gel) Patients apply curcumin-based gel topically TID approximately every 4-6 hours beginning on the first day of radiation therapy and continuing until 1 week after completion of radiation therapy.
Curcumin-based Gel: Applied topically
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies | 64 |
| Arm II (HPR Plus) Patients apply HPR Plus™ topically TID approximately every 4-6 hours beginning on the first day of radiation therapy and continuing until 1 week after completion of radiation therapy.
Dermatologic Complications Management: Apply HPR Plus topically
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies | 65 |
| Arm III (Placebo Gel) Patients apply placebo gel topically TID approximately every 4-6 hours beginning on the first day of radiation therapy and continuing until 1 week after completion of radiation therapy.
Laboratory Biomarker Analysis: Correlative studies
Placebo: Apply placebo gel topically
Questionnaire Administration: Ancillary studies | 62 |
| Total | 191 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Changed Mind | 0 | 1 | 0 |
| Overall Study | Did Not Start RT | 0 | 1 | 0 |
| Overall Study | Disliked Intervention | 1 | 1 | 1 |
| Overall Study | Disliked Study Procedures | 0 | 0 | 1 |
| Overall Study | Ineligible | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | No Reason | 1 | 0 | 1 |
| Overall Study | Personal Issues | 0 | 1 | 1 |
| Overall Study | Possibly Related Adverse Event | 0 | 0 | 1 |
| Overall Study | Related Adverse Event | 0 | 1 | 0 |
| Overall Study | Treatment or Change Delay | 0 | 0 | 1 |
| Overall Study | Unrelated Adverse Event | 1 | 0 | 3 |
| Overall Study | Withdrew (Unrelated Medical) | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Arm I (Curcumin-based Gel) | Arm II (HPR Plus) | Arm III (Placebo Gel) |
|---|---|---|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 10.3 | 59.0 years STANDARD_DEVIATION 11.2 | 60.7 years STANDARD_DEVIATION 10.5 | 59.8 years STANDARD_DEVIATION 9.3 |
| Breast Field Separation | 23.1 centimeters STANDARD_DEVIATION 4.6 | 22.6 centimeters STANDARD_DEVIATION 4 | 23.8 centimeters STANDARD_DEVIATION 4.2 | 22.8 centimeters STANDARD_DEVIATION 5.5 |
| Currently on Herceptin Treatment No | 170 Participants | 56 Participants | 56 Participants | 58 Participants |
| Currently on Herceptin Treatment Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Currently on Herceptin Treatment Yes | 19 Participants | 8 Participants | 8 Participants | 3 Participants |
| Currently on Hormone Therapy No | 148 Participants | 52 Participants | 48 Participants | 48 Participants |
| Currently on Hormone Therapy Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Currently on Hormone Therapy Yes | 41 Participants | 12 Participants | 16 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 186 Participants | 62 Participants | 63 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Location of Breast Cancer Left | 86 Participants | 29 Participants | 27 Participants | 30 Participants |
| Location of Breast Cancer Right | 103 Participants | 35 Participants | 37 Participants | 31 Participants |
| Location of Breast Cancer Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Marital Status Divorced | 30 Participants | 5 Participants | 9 Participants | 16 Participants |
| Marital Status Domestic Partner | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Marital Status Married | 119 Participants | 45 Participants | 37 Participants | 37 Participants |
| Marital Status Separated | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Marital Status Single | 18 Participants | 8 Participants | 8 Participants | 2 Participants |
| Marital Status Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Marital Status Widowed | 19 Participants | 5 Participants | 10 Participants | 4 Participants |
| Prior Chemotherapy No | 99 Participants | 30 Participants | 35 Participants | 34 Participants |
| Prior Chemotherapy Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Prior Chemotherapy Yes | 90 Participants | 34 Participants | 29 Participants | 27 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 21 Participants | 8 Participants | 9 Participants | 4 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 167 Participants | 55 Participants | 55 Participants | 57 Participants |
| Radiation Boost Planned No | 9 Participants | 4 Participants | 3 Participants | 2 Participants |
| Radiation Boost Planned Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Radiation Boost Planned Yes | 180 Participants | 60 Participants | 61 Participants | 59 Participants |
| Sex: Female, Male Female | 191 Participants | 64 Participants | 65 Participants | 62 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Stage of Disease DCIS | 28 Participants | 5 Participants | 12 Participants | 11 Participants |
| Stage of Disease Stage I | 85 Participants | 34 Participants | 29 Participants | 22 Participants |
| Stage of Disease Stage II | 54 Participants | 16 Participants | 18 Participants | 20 Participants |
| Stage of Disease Stage III | 20 Participants | 7 Participants | 5 Participants | 8 Participants |
| Stage of Disease Stage IV | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Stage of Disease Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Total Radiation Dose Prescribed | 59.0 Gray units STANDARD_DEVIATION 5.1 | 58.4 Gray units STANDARD_DEVIATION 5.6 | 59.5 Gray units STANDARD_DEVIATION 4.5 | 59.1 Gray units STANDARD_DEVIATION 5.2 |
| Type of Radiation 3D Conformal Whole Breast | 184 Participants | 63 Participants | 62 Participants | 59 Participants |
| Type of Radiation IMRT | 5 Participants | 1 Participants | 2 Participants | 2 Participants |
| Type of Radiation Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 1 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 / 65 | 0 / 62 |
| other Total, other adverse events | 8 / 64 | 3 / 65 | 5 / 62 |
| serious Total, serious adverse events | 3 / 64 | 2 / 65 | 6 / 62 |
Outcome results
Primary
Change in the Severity of Skin Reactions Using the Radiation Dermatitis Scale (RDS). Range: 0 (no Dermatitis) - 4 (Violaceous Erythema With Diffuse Desquamation Occurring in Sheets; Patchy Crusting; Superficial Ulceration)
The mean 1 week post-RT RDS score for each arm will be compared using ANOVA to determine if the topical interventions reduce the severity of skin reactions after completion of RT. The RDS score ranges from 0-4 with higher scores indicating worse outcome.
Time frame: Baseline to up to 1 week after completion of radiation therapy
Population: Note: Of the 64 who were randomized to Arm 1, 60 completed 1-week post; of the 65 who were randomized to Arm II, 58 completed 1-week post; of the 62 who were randomized to Arm III, 52 completed 1-week post.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Curcumin-based Gel) | Change in the Severity of Skin Reactions Using the Radiation Dermatitis Scale (RDS). Range: 0 (no Dermatitis) - 4 (Violaceous Erythema With Diffuse Desquamation Occurring in Sheets; Patchy Crusting; Superficial Ulceration) | 2.25 units on a scale | Standard Deviation 0.99 |
| Arm II (HPR Plus) | Change in the Severity of Skin Reactions Using the Radiation Dermatitis Scale (RDS). Range: 0 (no Dermatitis) - 4 (Violaceous Erythema With Diffuse Desquamation Occurring in Sheets; Patchy Crusting; Superficial Ulceration) | 2.16 units on a scale | Standard Deviation 0.92 |
| Arm III (Placebo Gel) | Change in the Severity of Skin Reactions Using the Radiation Dermatitis Scale (RDS). Range: 0 (no Dermatitis) - 4 (Violaceous Erythema With Diffuse Desquamation Occurring in Sheets; Patchy Crusting; Superficial Ulceration) | 2.15 units on a scale | Standard Deviation 0.96 |
p-value: 0.8591ANOVA
Primary
Incidence of Moist Desquamation (Present vs. Absent)
The degree to which each topical intervention decreases the incidence of moist desquamation will be examined using Fisher's exact test. Each agent's potential as a preventative intervention will be determined through comparison of the proportion of subjects with no to minimal radiation dermatitis within each arm using Fisher's exact test.
Time frame: Baseline up to completion of radiation therapy
Population: Note: Of the 64 who were randomized to Arm 1, 59 completed the study; of the 65 who were randomized to Arm II, 59 completed the study; of the 62 who were randomized to Arm III, 53 completed the study
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I (Curcumin-based Gel) | Incidence of Moist Desquamation (Present vs. Absent) | No Moist Desquamation | 44 Participants |
| Arm I (Curcumin-based Gel) | Incidence of Moist Desquamation (Present vs. Absent) | Moist Desquamation | 15 Participants |
| Arm II (HPR Plus) | Incidence of Moist Desquamation (Present vs. Absent) | No Moist Desquamation | 47 Participants |
| Arm II (HPR Plus) | Incidence of Moist Desquamation (Present vs. Absent) | Moist Desquamation | 12 Participants |
| Arm III (Placebo Gel) | Incidence of Moist Desquamation (Present vs. Absent) | No Moist Desquamation | 41 Participants |
| Arm III (Placebo Gel) | Incidence of Moist Desquamation (Present vs. Absent) | Moist Desquamation | 12 Participants |
p-value: 0.8048Fisher Exact
Primary
Mean Radiation Dermatitis Severity (RDS) Score. Range: 0 (no Dermatitis) - 4 (Violaceous Erythema With Diffuse Desquamation Occurring in Sheets; Patchy Crusting; Superficial Ulceration)
The mean 1 week post-RT RDS score for each arm will be compared using ANOVA to determine if the topical interventions reduce the severity of skin reactions at the end of RT. The RDS score ranges from 0-4 with higher scores indicating worse outcome.
Time frame: Baseline up to 1 week post radiation therapy
Population: Note: Of the 64 who were randomized to Arm 1, 59 completed the study; of the 65 who were randomized to Arm II, 59 completed the study; of the 62 who were randomized to Arm III, 53 completed the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Curcumin-based Gel) | Mean Radiation Dermatitis Severity (RDS) Score. Range: 0 (no Dermatitis) - 4 (Violaceous Erythema With Diffuse Desquamation Occurring in Sheets; Patchy Crusting; Superficial Ulceration) | 2.68 units on a scale | Standard Deviation 0.74 |
| Arm II (HPR Plus) | Mean Radiation Dermatitis Severity (RDS) Score. Range: 0 (no Dermatitis) - 4 (Violaceous Erythema With Diffuse Desquamation Occurring in Sheets; Patchy Crusting; Superficial Ulceration) | 2.64 units on a scale | Standard Deviation 0.74 |
| Arm III (Placebo Gel) | Mean Radiation Dermatitis Severity (RDS) Score. Range: 0 (no Dermatitis) - 4 (Violaceous Erythema With Diffuse Desquamation Occurring in Sheets; Patchy Crusting; Superficial Ulceration) | 2.63 units on a scale | Standard Deviation 0.69 |
p-value: 0.9306ANOVA