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

A Two-Part, Phase II Randomized Trial to Explore Topical Spironolactone to Prevent/Attenuate Rash From Epidermal Growth Factor Receptor Inhibitors (Panitumumab and Cetuximab) in Advanced Cancer Patients

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.

Study Overview

• Status: Completed
• Conditions: Advanced Malignant Neoplasm; Dermatologic Complication
• Intervention / Treatment: Other: Questionnaire Administration; Drug: Spironolactone; Other: Placebo; Drug: Doxycycline; Procedure: Management of Therapy Complications; Drug: Sunscreen; Drug: Therapeutic Hydrocortisone

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Iowa-Wide Oncology Research Coalition NCORP
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
  • Minnesota
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center at Saint Cloud Hospital
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (Study I); Patients apply spironolactone topically to face BID for 4 weeks.	Other: Questionnaire Administration; Ancillary studies; Drug: Spironolactone; Given topically; Other Names: Aldactone; 17-Hydroxy-7alpha-mercapto-3-oxo-17alpha-pregn-4-ene-21-carboxylic Acid, gamma Lactone, Acetate; SC 9420; SPL
Experimental: Arm I (Study II); Patients apply spironolactone topically to face and body BID for 4 weeks.	Other: Questionnaire Administration; Ancillary studies; Drug: Spironolactone; Given topically; Other Names: Aldactone; 17-Hydroxy-7alpha-mercapto-3-oxo-17alpha-pregn-4-ene-21-carboxylic Acid, gamma Lactone, Acetate; SC 9420; SPL
Placebo Comparator: Arm II (Study I); Patients apply placebo topically to face BID for 4 weeks.	Other: Questionnaire Administration; Ancillary studies; Other: Placebo; Given topically; Other Names: placebo therapy; PLCB; sham therapy
Active Comparator: Arm II (Study II); 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.	Other: Questionnaire Administration; Ancillary studies; Drug: Doxycycline; Given PO; Other Names: Doxycycline Monohydrate; Procedure: Management of Therapy Complications; Moisturizer given topically; Drug: Sunscreen; Given topically; Other Names: Sunblock; Drug: Therapeutic Hydrocortisone; Given topically; Other Names: Aeroseb-HC; Barseb HC; Barseb-HC; Cetacort; Cort-Dome; Cortef; Cortenema; Cortifan; Cortisol; Cortispray; Cortril; Dermacort; Domolene; Eldecort; Hautosone; Heb-Cort; Hydrocortone; Hytone; Komed-HC; Nutracort; Proctocort; Rectoid; hydrocortisone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	At 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	At 4 weeks

Collaborators and Investigators

• Sponsor: Academic and Community Cancer Research United
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Aminah Jatoi, Academic and Community Cancer Research United

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2012
• Primary Completion (Actual): May 9, 2014
• Study Completion (Actual): June 13, 2014

Study Registration Dates

• First Submitted: August 27, 2012
• First Submitted That Met QC Criteria: May 29, 2013
• First Posted (Estimate): June 4, 2013

Study Record Updates

• Last Update Posted (Actual): January 9, 2020
• Last Update Submitted That Met QC Criteria: January 6, 2020
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Anti-Infective Agents; Anti-Inflammatory Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Natriuretic Agents; Dermatologic Agents; Anti-Bacterial Agents; Diuretics; Hormone Antagonists; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Radiation-Protective Agents; Doxycycline; Spironolactone; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Sunscreening Agents
• Other Study ID Numbers: RC09C8 (Other Identifier: Academic and Community Cancer Research United); P30CA015083 (U.S. NIH Grant/Contract); NCI-2012-01275 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No