Advanced Malignant Neoplasm, Dermatologic Complication
Conditions
Brief summary
This randomized phase II trial studies how well giving spironolactone works in preventing rash in patients with cancer that has spread to other places in the body and are receiving panitumumab and cetuximab. Spironolactone may prevent endothelial growth factor receptor (EGFR) inhibitor-induced skin rash.
Detailed description
PRIMARY OBJECTIVES: I. To determine feasibility of the administration of topical spironolactone versus placebo in this patient population. (Study I) II. To further explore the efficacy of the topical spironolactone to prevent/attenuate rash from EGFR inhibitors. (Study II) SECONDARY OBJECTIVES: I. To explore efficacy of the spironolactone versus placebo. (Study I) II. To describe the efficacy of a Modified Preemptive Therapy Regimen intervention. (Study II) III. To explore the adverse event profile of spironolactone and the Modified Preemptive Therapy Regimen intervention. (Study II) IV. To explore patient reported outcomes of patients using spironolactone and a Modified Preemptive Therapy Regimen intervention. (Study II) V. To explore long term (8 week) effect of the 4 week treatment of spironolactone and a Modified Preemptive Therapy Regimen intervention on EFGR induced rash. (Study II) OUTLINE: STUDY I: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients apply spironolactone topically to face twice daily (BID) for 4 weeks. ARM II: Patients apply placebo topically to face BID for 4 weeks. STUDY II: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients apply spironolactone topically to face and body BID for 4 weeks ARM II: Patients undergo modified preemptive therapy regimen consisting of skin moisturizer topically BID, sunscreen topically before going outside, hydrocortisone topically once daily (QD), and doxycycline orally (PO) BID for 4 weeks. After completion of study, patients are followed up for 4 weeks.
Interventions
DRUGDoxycycline
Given PO
PROCEDUREManagement of Therapy Complications
Moisturizer given topically
OTHERPlacebo
Given topically
OTHERQuestionnaire Administration
Ancillary studies
DRUGSpironolactone
Given topically
DRUGSunscreen
Given topically
DRUGTherapeutic Hydrocortisone
Given topically
Sponsors
National Cancer Institute (NCI)
Academic and Community Cancer Research United
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Scheduled to start panitumumab or cetuximab; patients must not have been on the EGFR agent prior to randomization * Ability to reliably apply topical spironolactone/placebo twice a day to the face * Ability to complete questionnaire(s) by themselves or with assistance * For study 2 only, patients must be willing to avoid sun exposure for one month from registration * Creatinine =\< 1.5 x upper limit of normal (UNL) * For Study 2 only, ability to apply topical creams to the entire face and body
Exclusion criteria
* Prior allergic reaction or severe intolerance to spironolactone * Any rash at the time of randomization * Cutaneous metastases * Any other disorder that may predispose to hyperkalemia in the opinion of the treating oncologist * Use of topical corticosteroids at the time of study or their anticipated use in the next 8 weeks; (it is acknowledged that patients may be starting these agents pre-emptively as part of this protocol) * For study 2 only, previous intolerance of sunscreen or any of the other components of the Modified Preemptive Therapy Regimen (a moisturizer or oral doxycycline)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Reporting a Grade 2+ Adverse Event Attributed to Spironolactone (Study I) | At 8 weeks | Adverse events were collected at the end of one 4-week cycle and one 4-week observation period according to the Common Terminology Criteria for Adverse Events (CTCAE) CTEP Version 4.0. The number of patients reporting a grade 2+ adverse event attributed to spironolactone is reported here. |
| Incidence of Truncal/Extremity Rash of Any Grade in Patients in the Spironolactone Arm (Study I) | At 4 weeks | Adverse events were collected at the end of each 4-week cycle according to the Common Terminology Criteria for Adverse Events (CTCAE) CTEP Version 4.0. The number of patients reporting a truncal/extremity adverse event is reported here. The treatment will be considered feasible if at least 50% of patients in the spironolactone arm develop a truncal/extremity rash of any grade at the end of 4 weeks. |
| Percentage of Patients in the Spironolactone Arm Who Complete the 4-week Study Intervention (Study I) | At 4 weeks | The number of patients able to complete the 4-week study intervention and the 4-week observation period are reported. |
| Efficacy of the Spironolactone Treatment to Prevent/Attenuate Rash From EGFR Inhibitors in This Patient Population Defined as Absence of Any Grade 2 or Worse Rash (Study II) | At 4 weeks | The primary analysis will be descriptive in nature, and will involve an intent-to-treat analysis at the end of week 4. Patients will be categorized dichotomously according to healthcare provider reported grade 2 or worse rash. The absence of any grade 2 or worse rash will be a success and the existence of any such rash will be a failure. Patients who do not complete the 4 week treatment will be considered a failure. Point estimates and 95% confidence limits will be calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Spironolactone and Placebo Measured by the Use of the Brief Pictorial Rash Incidence Questionnaire (Study I) | At 4 weeks | Patients will be dichotomously categorized as a success if no rash is reported and a failure if rash exists at the end of 4 weeks. The number of patients that successfully completed 4 weeks of treatment and reported no rash on the Brief Pictorial Rash Incidence Questionnaire are reported. |
| Patient Reported Outcomes as Measured by the Change From Baseline in the SKINDEX-16 Total Score (Study II) | At 4 weeks | Total scores from the SKINDEX-16 will be compared from baseline to week 4. Comparisons between treatment arms will be made by t-tests. |
| Efficacy of the Modified Preemptive Therapy Regimen, Calculated and Analyzed Analogously to the Efficacy of the Spironolactone (Study II) | At 4 weeks | All secondary endpoints will be reported descriptively using frequency statistics and single sample t-tests. Outcomes with respect to baseline covariates will also be explored. |
| Efficacy of the Spironolactone Treatment to Prevent/Attenuate Rash From EGFR Inhibitors in This Patient Population Defined as Absence of Any Grade 2 or Worse Rash (Study II) | At 8 weeks | This analysis will be descriptive in nature, and will involve an intent-to-treat analysis at the end of week 8. Patients will be categorized dichotomously according to healthcare provider reported grade 2 or worse rash. The absence of any grade 2 or worse rash will be a success and the existence of any such rash will be a failure. Patients who do not complete the 8 week treatment will be considered a failure. Point estimates and 95% confidence limits will be calculated. |
| Incidence of Healthcare Provider Reported Adverse Events (Study II) | At 8 weeks | All secondary endpoints will be reported descriptively using frequency statistics and single sample t-tests. Outcomes with respect to baseline covariates will also be explored. |
Countries
United States
Participant flow
Recruitment details
Study II was never opened due to the accrual rate in Study I.
Participants by arm
| Arm | Count |
|---|---|
| Study I: Spironolactone Patients apply spironolactone topically to face BID for 4 weeks. | 8 |
| Study I: Placebo Patients apply placebo topically to face BID for 4 weeks. | 9 |
| Study II: Spironolactone Patients apply spironolactone topically to face and body BID for 4 weeks. | 0 |
| Study II: Modified Therapy Patients receive modified preemptive therapy regimen consisting of skin moisturizer topically BID, sunscreen topically as needed, hydrocortisone topically QD, and doxycycline PO BID for 4 weeks. | 0 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Study I: Spironolactone | Study I: Placebo | Total |
|---|---|---|---|
| Age, Continuous | 65.0 years | 60.6 years | 62.6 years |
| Region of Enrollment United States | 8 participants | 9 participants | 17 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 9 | 0 / 8 |
| other Total, other adverse events | 8 / 9 | 6 / 8 |
| serious Total, serious adverse events | 2 / 9 | 2 / 8 |
Outcome results
Primary
Efficacy of the Spironolactone Treatment to Prevent/Attenuate Rash From EGFR Inhibitors in This Patient Population Defined as Absence of Any Grade 2 or Worse Rash (Study II)
The primary analysis will be descriptive in nature, and will involve an intent-to-treat analysis at the end of week 4. Patients will be categorized dichotomously according to healthcare provider reported grade 2 or worse rash. The absence of any grade 2 or worse rash will be a success and the existence of any such rash will be a failure. Patients who do not complete the 4 week treatment will be considered a failure. Point estimates and 95% confidence limits will be calculated.
Time frame: At 4 weeks
Population: Study II was not conducted.
Primary
Incidence of Truncal/Extremity Rash of Any Grade in Patients in the Spironolactone Arm (Study I)
Adverse events were collected at the end of each 4-week cycle according to the Common Terminology Criteria for Adverse Events (CTCAE) CTEP Version 4.0. The number of patients reporting a truncal/extremity adverse event is reported here. The treatment will be considered feasible if at least 50% of patients in the spironolactone arm develop a truncal/extremity rash of any grade at the end of 4 weeks.
Time frame: At 4 weeks
Population: All patients that began protocol treatment are included in this endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study I: Spironolactone | Incidence of Truncal/Extremity Rash of Any Grade in Patients in the Spironolactone Arm (Study I) | 6 Participants |
| Study I: Placebo | Incidence of Truncal/Extremity Rash of Any Grade in Patients in the Spironolactone Arm (Study I) | 6 Participants |
Primary
Number of Patients Reporting a Grade 2+ Adverse Event Attributed to Spironolactone (Study I)
Adverse events were collected at the end of one 4-week cycle and one 4-week observation period according to the Common Terminology Criteria for Adverse Events (CTCAE) CTEP Version 4.0. The number of patients reporting a grade 2+ adverse event attributed to spironolactone is reported here.
Time frame: At 8 weeks
Population: All patients that began study treatment were included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study I: Spironolactone | Number of Patients Reporting a Grade 2+ Adverse Event Attributed to Spironolactone (Study I) | 0 Participants |
| Study I: Placebo | Number of Patients Reporting a Grade 2+ Adverse Event Attributed to Spironolactone (Study I) | 0 Participants |
Primary
Percentage of Patients in the Spironolactone Arm Who Complete the 4-week Study Intervention (Study I)
The number of patients able to complete the 4-week study intervention and the 4-week observation period are reported.
Time frame: At 4 weeks
Population: All patients that began Study I treatment were included in this endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study I: Spironolactone | Percentage of Patients in the Spironolactone Arm Who Complete the 4-week Study Intervention (Study I) | 4 Participants |
| Study I: Placebo | Percentage of Patients in the Spironolactone Arm Who Complete the 4-week Study Intervention (Study I) | 0 Participants |
Secondary
Efficacy of Spironolactone and Placebo Measured by the Use of the Brief Pictorial Rash Incidence Questionnaire (Study I)
Patients will be dichotomously categorized as a success if no rash is reported and a failure if rash exists at the end of 4 weeks. The number of patients that successfully completed 4 weeks of treatment and reported no rash on the Brief Pictorial Rash Incidence Questionnaire are reported.
Time frame: At 4 weeks
Population: All patients that began study treatment are included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study I: Spironolactone | Efficacy of Spironolactone and Placebo Measured by the Use of the Brief Pictorial Rash Incidence Questionnaire (Study I) | 1 participants |
| Study I: Placebo | Efficacy of Spironolactone and Placebo Measured by the Use of the Brief Pictorial Rash Incidence Questionnaire (Study I) | 2 participants |
Secondary
Efficacy of the Modified Preemptive Therapy Regimen, Calculated and Analyzed Analogously to the Efficacy of the Spironolactone (Study II)
All secondary endpoints will be reported descriptively using frequency statistics and single sample t-tests. Outcomes with respect to baseline covariates will also be explored.
Time frame: At 4 weeks
Population: Study II was not conducted.
Secondary
Efficacy of the Spironolactone Treatment to Prevent/Attenuate Rash From EGFR Inhibitors in This Patient Population Defined as Absence of Any Grade 2 or Worse Rash (Study II)
This analysis will be descriptive in nature, and will involve an intent-to-treat analysis at the end of week 8. Patients will be categorized dichotomously according to healthcare provider reported grade 2 or worse rash. The absence of any grade 2 or worse rash will be a success and the existence of any such rash will be a failure. Patients who do not complete the 8 week treatment will be considered a failure. Point estimates and 95% confidence limits will be calculated.
Time frame: At 8 weeks
Population: Study II was not conducted.
Secondary
Incidence of Healthcare Provider Reported Adverse Events (Study II)
All secondary endpoints will be reported descriptively using frequency statistics and single sample t-tests. Outcomes with respect to baseline covariates will also be explored.
Time frame: At 8 weeks
Population: Study II was not conducted.
Secondary
Patient Reported Outcomes as Measured by the Change From Baseline in the SKINDEX-16 Total Score (Study II)
Total scores from the SKINDEX-16 will be compared from baseline to week 4. Comparisons between treatment arms will be made by t-tests.
Time frame: At 4 weeks
Population: Study II was not conducted.