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.

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.

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)