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

Advanced Malignant Neoplasm Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01867294
• Other study ID #: RC09C8
• Secondary ID: NCI-2012-01275RC
• Status: Completed
• Phase: Phase 2
• Start date: August 31, 2012
• Est. completion date: June 13, 2014

Study information

• Verified date: January 2018
• Source: Academic and Community Cancer Research United
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT02257086

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: June 13, 2014
• Est. primary completion date: May 9, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Advanced Malignant Neoplasm
• Dermatologic Complication
• Neoplasms

Intervention

Drug:
• Doxycycline
Given PO

Procedure:
• Management of Therapy Complications
Moisturizer given topically

Other:
• Placebo
Given topically
• Questionnaire Administration
Ancillary studies

Drug:
• Spironolactone
Given topically
• Sunscreen
Given topically
• Therapeutic Hydrocortisone
Given topically

Locations

Country	Name	City	State
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota
United States	Carle Cancer Center	Urbana	Illinois
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Academic and Community Cancer Research United	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	At 8 weeks
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.	At 4 weeks
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.	At 4 weeks
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.	At 4 weeks
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.	At 4 weeks
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.	At 4 weeks
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.	At 8 weeks
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.	At 8 weeks
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.	At 4 weeks