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

NCT01867294 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: RC09C8NCI-2012-01275P30CA015083
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 5

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.

Conditions

Advanced Malignant Neoplasm; Dermatologic Complication

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (5)

• Efficacy of Spironolactone and Placebo Measured by the Use of the Brief Pictorial Rash Incidence Questionnaire (Study I)

  At 4 weeks

• Efficacy of the Modified Preemptive Therapy Regimen, Calculated and Analyzed Analogously to the Efficacy of the Spironolactone (Study II)

  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)

  At 8 weeks

• Incidence of Healthcare Provider Reported Adverse Events (Study II)

  At 8 weeks

• Patient Reported Outcomes as Measured by the Change From Baseline in the SKINDEX-16 Total Score (Study II)

  At 4 weeks

Study Arms (4)

Arm I (Study I)

EXPERIMENTAL

Patients apply spironolactone topically to face BID for 4 weeks.

Other: Questionnaire Administration; Drug: Spironolactone

Arm I (Study II)

EXPERIMENTAL

Patients apply spironolactone topically to face and body BID for 4 weeks.

Other: Questionnaire Administration; Drug: Spironolactone

Arm II (Study I)

PLACEBO COMPARATOR

Patients apply placebo topically to face BID for 4 weeks.

Other: Placebo; Other: Questionnaire Administration

Arm II (Study II)

ACTIVE COMPARATOR

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

Interventions

Doxycycline DRUG

Given PO

Also known as: Doxycycline Monohydrate

Arm II (Study II)

Management of Therapy Complications PROCEDURE

Moisturizer given topically

Arm II (Study II)

Placebo OTHER

Given topically

Also known as: placebo therapy, PLCB, sham therapy

Arm II (Study I)

Questionnaire Administration OTHER

Ancillary studies

Arm I (Study I); Arm I (Study II); Arm II (Study I); Arm II (Study II)

Spironolactone DRUG

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

Arm I (Study I); Arm I (Study II)

Sunscreen DRUG

Given topically

Also known as: Sunblock

Arm II (Study II)

Therapeutic Hydrocortisone DRUG

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

Arm II (Study II)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Iowa-Wide Oncology Research Coalition NCORP

Des Moines, Iowa, 50309, United States

Location

Cancer Center of Kansas - Wichita

Wichita, Kansas, 67214, United States

Location

Coborn Cancer Center at Saint Cloud Hospital

Saint Cloud, Minnesota, 56303, United States

Location

Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

MeSH Terms

Interventions

Doxycycline; Spironolactone; Acetates; Sunscreening Agents; Hydrocortisone

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Lactones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Acids, Acyclic; Carboxylic Acids; Fatty Acids, Volatile; Fatty Acids; Lipids; Radiation-Protective Agents; Protective Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Dermatologic Agents; Therapeutic Uses; Cosmetics; Specialty Uses of Chemicals; Pregnenediones; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Results Point of Contact

• Title: Aminah Jatoi, M.D.
• Organization: Mayo Clinic

jatoi.aminah@mayo.edu

507.284.1623

Study Officials

• Aminah Jatoi

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 27, 2012
• First Posted: June 4, 2013
• Study Start: August 31, 2012
• Primary Completion: May 9, 2014
• Study Completion: June 13, 2014
• Last Updated: January 9, 2020
• Results First Posted: January 9, 2020

Record last verified: 2018-01

Locations

US (5)