Trial Outcomes & Findings for Spironolactone in Preventing Rash in Patients With Advanced Cancer Receiving Panitumumab and Cetuximab (NCT NCT01867294)

Last Updated: 2020-01-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

At 8 weeks

Results posted on

2020-01-09

Participant Flow

Study II was never opened due to the accrual rate in Study I.

Participant milestones

Participant milestones
Measure	Study I: Spironolactone Patients apply spironolactone topically to face BID for 4 weeks.	Study I: Placebo Patients apply placebo topically to face BID for 4 weeks.
Overall Study STARTED	9	10
Overall Study COMPLETED	8	9
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Study I: Spironolactone Patients apply spironolactone topically to face BID for 4 weeks.	Study I: Placebo Patients apply placebo topically to face BID for 4 weeks.	Study II: Spironolactone Patients apply spironolactone topically to face and body BID for 4 weeks.	Study II: Modified Therapy 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.
Overall Study Withdrawal by Subject	1	1	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study I: Spironolactone n=8 Participants Patients apply spironolactone topically to face BID for 4 weeks.	Study I: Placebo n=9 Participants Patients apply placebo topically to face BID for 4 weeks.	Study II: Spironolactone Patients apply spironolactone topically to face and body BID for 4 weeks.	Study II: Modified Therapy 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.	Total n=17 Participants Total of all reporting groups
Age, Continuous	65.0 years n=5 Participants	60.6 years n=7 Participants	—	—	62.6 years n=21 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	—	—	4 Participants n=21 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	7 Participants n=7 Participants	—	—	13 Participants n=21 Participants
Region of Enrollment United States	8 participants n=5 Participants	9 participants n=7 Participants	—	—	17 participants n=21 Participants

PRIMARY outcome

Timeframe: At 8 weeks

Population: All patients that began study treatment were included in this analysis.

Outcome measures

Outcome measures
Measure	Study I: Spironolactone n=8 Participants Patients apply spironolactone topically to face BID for 4 weeks.	Study I: Placebo n=9 Participants Patients apply placebo topically to face BID for 4 weeks.	Study II: Spironolactone Patients apply spironolactone topically to face and body BID for 4 weeks.	Study II: Modified Therapy 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.
Number of Patients Reporting a Grade 2+ Adverse Event Attributed to Spironolactone (Study I)	0 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: At 4 weeks

Population: All patients that began protocol treatment are included in this endpoint.

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.

Outcome measures

Outcome measures
Measure	Study I: Spironolactone n=8 Participants Patients apply spironolactone topically to face BID for 4 weeks.	Study I: Placebo n=9 Participants Patients apply placebo topically to face BID for 4 weeks.	Study II: Spironolactone Patients apply spironolactone topically to face and body BID for 4 weeks.	Study II: Modified Therapy 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.
Incidence of Truncal/Extremity Rash of Any Grade in Patients in the Spironolactone Arm (Study I)	6 Participants	6 Participants	—	—

PRIMARY outcome

Timeframe: At 4 weeks

Population: All patients that began Study I treatment were included in this endpoint.

The number of patients able to complete the 4-week study intervention and the 4-week observation period are reported.

Outcome measures

Outcome measures
Measure	Study I: Spironolactone n=8 Participants Patients apply spironolactone topically to face BID for 4 weeks.	Study I: Placebo Patients apply placebo topically to face BID for 4 weeks.	Study II: Spironolactone Patients apply spironolactone topically to face and body BID for 4 weeks.	Study II: Modified Therapy 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.
Percentage of Patients in the Spironolactone Arm Who Complete the 4-week Study Intervention (Study I)	4 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: At 4 weeks

Population: Study II was not conducted.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 4 weeks

Population: All patients that began study treatment are included in this analysis.

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.

Outcome measures

Outcome measures
Measure	Study I: Spironolactone n=8 Participants Patients apply spironolactone topically to face BID for 4 weeks.	Study I: Placebo n=9 Participants Patients apply placebo topically to face BID for 4 weeks.	Study II: Spironolactone Patients apply spironolactone topically to face and body BID for 4 weeks.	Study II: Modified Therapy 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.
Efficacy of Spironolactone and Placebo Measured by the Use of the Brief Pictorial Rash Incidence Questionnaire (Study I)	1 participants	2 participants	—	—

SECONDARY outcome

Timeframe: At 4 weeks

Population: Study II was not conducted.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 8 weeks

Population: Study II was not conducted.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 8 weeks

Population: Study II was not conducted.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 4 weeks

Population: Study II was not conducted.

Total scores from the SKINDEX-16 will be compared from baseline to week 4. Comparisons between treatment arms will be made by t-tests.

Outcome measures

Outcome data not reported

Adverse Events

Study I: Placebo

Serious events: 2 serious events

Other events: 8 other events

Deaths: 2 deaths

Study I: Spironolactone

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Aminah Jatoi, M.D.

Mayo Clinic

Phone: 507.284.1623

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Study I: Placebo n=9 participants at risk Patients apply placebo topically to face BID for 4 weeks.	Study I: Spironolactone n=8 participants at risk .Patients apply spironolactone topically to face BID for 4 weeks.
Blood and lymphatic system disorders Anemia	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Gastrointestinal disorders Abdominal distension	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Gastrointestinal disorders Abdominal pain	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Gastrointestinal disorders Ascites	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Gastrointestinal disorders Ileus	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Gastrointestinal disorders Mucositis oral	0.00% 0/9 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	12.5% 1/8 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
General disorders Death NOS	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
General disorders Fatigue	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
General disorders Multi-organ failure	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Infections and infestations Sepsis	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Injury, poisoning and procedural complications Gastrointestinal stoma necrosis	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Injury, poisoning and procedural complications Intraoperative hemorrhage	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Investigations Blood bilirubin increased	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Investigations Creatinine increased	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Investigations INR increased	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Investigations Lymphocyte count decreased	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Metabolism and nutrition disorders Dehydration	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Metabolism and nutrition disorders Hyperglycemia	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Metabolism and nutrition disorders Hypoalbuminemia	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Metabolism and nutrition disorders Hypocalcemia	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Metabolism and nutrition disorders Hypokalemia	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Renal and urinary disorders Acute kidney injury	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Respiratory, thoracic and mediastinal disorders Hypoxia	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Respiratory, thoracic and mediastinal disorders Respiratory failure	11.1% 1/9 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	0.00% 0/8 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/9 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	12.5% 1/8 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/9 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.	12.5% 1/8 • Number of events 1 • Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks. Adverse events were assessed after one 4 week cycle, and after one 4-week observation prior for a maximum of up to 8 weeks.