A Phase 2 interventional study of Doxycycline and Management of Therapy Complications in Advanced Malignant Neoplasm and Dermatologic Complication, sponsored by Academic and Community Cancer Research United. Completed at 5 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-01-09.
Sponsored by Academic and Community Cancer Research United · Phase 2, Interventional, and Supportive care
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.
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.
9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.
This study's enrollment of 19 is below the median of 50 across 7,253 interventional studies indexed under Neoplasms.
Browse Neoplasms studies →Academic and Community Cancer Research United is the lead sponsor of 49 studies on the registry; 5 are open to participants now.
Of its 13 completed or terminated interventional studies of FDA-regulated products, 12 (92%) have results posted.
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Exclusion Criteria:
Patients apply spironolactone topically to face BID for 4 weeks.
Other: Questionnaire Administration · Drug: Spironolactone
Patients apply spironolactone topically to face and body BID for 4 weeks.
Other: Questionnaire Administration · Drug: Spironolactone
Patients apply placebo topically to face BID for 4 weeks.
Other: Placebo · Other: Questionnaire Administration
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.
Drug: Doxycycline · Procedure: Management of Therapy Complications · Other: Questionnaire Administration · Drug: Sunscreen · Drug: Therapeutic Hydrocortisone
Given PO
Also known as: Doxycycline Monohydrate
Moisturizer given topically
Given topically
Also known as: placebo therapy, PLCB, sham therapy
Ancillary studies
Given topically
Also known as: 17-Hydroxy-7alpha-mercapto-3-oxo-17alpha-pregn-4-ene-21-carboxylic Acid, gamma Lactone, Acetate, Aldactone, SC 9420, SPL
Given topically
Also known as: Sunblock
Given topically
Also known as: Aeroseb-HC, Barseb HC, Barseb-HC, Cetacort, Cort-Dome, Cortef, Cortenema, Cortifan, Cortisol, Cortispray, Cortril, Dermacort, Domolene, Eldecort, Hautosone, Heb-Cort, hydrocortisone, Hydrocortone, Hytone, Komed-HC, Nutracort, Proctocort, Rectoid
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
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
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
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
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
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
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
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
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
Study II was never opened due to the accrual rate in Study I.
| Milestone | Study I: Spironolactone | Study I: Placebo | Study II: Spironolactone | Study II: Modified Therapy |
|---|---|---|---|---|
| Started | 9 | 10 | 0 | 0 |
| Completed | 8 | 9 | 0 | 0 |
| Not completed | 1 | 1 | 0 | 0 |
| Withdrew: Withdrawal by subject | 1 | 1 | 0 | 0 |
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.
| Participants | Study I: Spironolactone | Study I: Placebo | Study II: Spironolactone | Study II: Modified Therapy |
|---|---|---|---|---|
| Number of Patients Reporting a Grade 2+ Adverse Event Attributed to Spironolactone (Study I) | 0 | 0 | — | — |
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.
| Participants | Study I: Spironolactone | Study I: Placebo | Study II: Spironolactone | Study II: Modified Therapy |
|---|---|---|---|---|
| Incidence of Truncal/Extremity Rash of Any Grade in Patients in the Spironolactone Arm (Study I) | 6 | 6 | — | — |
The number of patients able to complete the 4-week study intervention and the 4-week observation period are reported.
| Participants | Study I: Spironolactone | Study I: Placebo | Study II: Spironolactone | Study II: Modified Therapy |
|---|---|---|---|---|
| Percentage of Patients in the Spironolactone Arm Who Complete the 4-week Study Intervention (Study I) | 4 | 0 | — | — |
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.
No measurements were reported for this outcome.
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.
| participants | Study I: Spironolactone | Study I: Placebo | Study II: Spironolactone | Study II: Modified Therapy |
|---|---|---|---|---|
| Efficacy of Spironolactone and Placebo Measured by the Use of the Brief Pictorial Rash Incidence Questionnaire (Study I) | 1 | 2 | — | — |
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
Total scores from the SKINDEX-16 will be compared from baseline to week 4. Comparisons between treatment arms will be made by t-tests.
No measurements were reported for this outcome.
Collected over Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Study I: Placebo | 2/9 (22.2%) | 2/9 (22.2%) | 8/9 (88.9%) |
| Study I: Spironolactone | 0/8 (0%) | 2/8 (25%) | 6/8 (75%) |
| Event | Study I: Placebo | Study I: Spironolactone |
|---|---|---|
| Mucositis oralGastrointestinal disorders | 0/9 | 1/8 |
| PruritusSkin and subcutaneous tissue disorders | 0/9 | 1/8 |
| Rash maculo-papularSkin and subcutaneous tissue disorders | 0/9 | 1/8 |
| AnemiaBlood and lymphatic system disorders | 1/9 | 0/8 |
| Abdominal distensionGastrointestinal disorders | 1/9 | 0/8 |
| Abdominal painGastrointestinal disorders | 1/9 | 0/8 |
| AscitesGastrointestinal disorders | 1/9 | 0/8 |
| IleusGastrointestinal disorders | 1/9 | 0/8 |
| Death NOSGeneral disorders | 1/9 | 0/8 |
| FatigueGeneral disorders | 1/9 | 0/8 |
| Event | Study I: Placebo | Study I: Spironolactone |
|---|---|---|
| Rash maculo-papularSkin and subcutaneous tissue disorders | 6/9 | 6/8 |
| PruritusSkin and subcutaneous tissue disorders | 6/9 | 5/8 |
| Lymphocyte count decreasedInvestigations | 2/9 | 0/8 |
| Neutrophil count decreasedInvestigations | 0/9 | 1/8 |
| White blood cell decreasedInvestigations | 0/9 | 1/8 |
| HypokalemiaMetabolism and nutrition disorders | 0/9 | 1/8 |
| AnemiaBlood and lymphatic system disorders | 1/9 | 0/8 |
| Hearing impairedEar and labyrinth disorders | 1/9 | 0/8 |
| Abdominal painGastrointestinal disorders | 1/9 | 0/8 |
| CholecystitisHepatobiliary disorders | 1/9 | 0/8 |
All patients that were treated and eligible for endpoint analysis were include in baseline characteristics. One patient from Study I: Spironolactone and one from Study I: Placebo withdrew from study participation prior to receiving any study treatment.
| Age, Continuous(years) | Study I: Spironolactone | Study I: Placebo | Study II: Spironolactone | Study II: Modified Therapy | Total |
|---|---|---|---|---|---|
| Median | 65.0 (55.0 to 77.0) | 60.6 (39.0 to 82.0) | — | — | 62.6 (39 to 82) |
| Sex: Female, Male(Participants) | Study I: Spironolactone | Study I: Placebo | Study II: Spironolactone | Study II: Modified Therapy | Total |
|---|---|---|---|---|---|
| Female | 2 | 2 | — | — | 4 |
| Male | 6 | 7 | — | — | 13 |
| Region of Enrollment(participants) | Study I: Spironolactone | Study I: Placebo | Study II: Spironolactone | Study II: Modified Therapy | Total |
|---|---|---|---|---|---|
| United States | 8 | 9 | — | — | 17 |
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