Spironolactone in Preventing Rash in Patients With Advanced Cancer Receiving Panitumumab and Cetuximab

Phase 2

Completed

Conditions: Advanced Malignant Neoplasm
Dermatologic Complication

Interventions: Other: Placebo
Other: Questionnaire Administration
Drug: Doxycycline
Drug: Spironolactone
Procedure: Management of Therapy Complications
Drug: Sunscreen
Drug: Therapeutic Hydrocortisone

Registration Number: NCT01867294

Lead Sponsor: Academic and Community Cancer Research United

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (Study II)	Therapeutic Hydrocortisone	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.
Arm I (Study I)	Spironolactone	Patients apply spironolactone topically to face BID for 4 weeks.
Arm II (Study I)	Placebo	Patients apply placebo topically to face BID for 4 weeks.
Arm I (Study I)	Questionnaire Administration	Patients apply spironolactone topically to face BID for 4 weeks.
Arm I (Study II)	Questionnaire Administration	Patients apply spironolactone topically to face and body BID for 4 weeks.
Arm II (Study I)	Questionnaire Administration	Patients apply placebo topically to face BID for 4 weeks.
Arm II (Study II)	Sunscreen	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.
Arm II (Study II)	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.
Arm II (Study II)	Management of Therapy Complications	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.
Arm II (Study II)	Doxycycline	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.
Arm I (Study II)	Spironolactone	Patients apply spironolactone topically to face and body BID for 4 weeks.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.

Trial Locations

Locations (5): Carle Cancer Center
🇺🇸
Urbana, Illinois, United States
Iowa-Wide Oncology Research Coalition NCORP
🇺🇸
Des Moines, Iowa, United States
Cancer Center of Kansas - Wichita
🇺🇸
Wichita, Kansas, United States
Coborn Cancer Center at Saint Cloud Hospital
🇺🇸
Saint Cloud, Minnesota, United States
Marshfield Clinic
🇺🇸
Marshfield, Wisconsin, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States