Trial Outcomes & Findings for Pyridoxine and Topical Urea/Lactic Acid-Based Cream in Preventing Hand-Foot Syndrome in Patients Receiving Capecitabine for Breast Cancer or Other Cancer (NCT NCT00296036)
NCT ID: NCT00296036
Last Updated: 2017-03-16
Results Overview
A patient self-reported hand-foot syndrome (HFSD), also known as palmar-plantar erythrodysesthesia, was completed daily while applying the cream. Patients rated skin severity symptoms individually in their hands and in their feet. Definitions of symptoms, which were based on Common Terminology Criteria for Adverse Events (CTCAE) v3.0, were provided to patients. The number of patients reporting moderate to severe symptoms in either hands or feet were tabulated and percentages are reported.
COMPLETED
PHASE3
137 participants
First 3 weeks of treatment
2017-03-16
Participant Flow
This trial was originally designed as a two-by-two factorial trial to test if urea/lactic acid-based cream and/or oral pyridoxine (B6) could decrease capecitabine-caused HFS. After results from another study found B6 and capecitabine combination ineffective in preventing HFS, the study was amended to a two-arm, randomized clinical trial.
Participant milestones
| Measure |
Arm I: (Urea/Lactic Acid +Vit B6)
Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily and oral pyridoxine once daily on days 1-21.
|
Arm II: (Urea/Lactic Acid + Placebo)
Patients receive topical urea/lactic acid-based cream as in arm I (closed to accrual as of 10/24/2007) and oral placebo once daily on days 1-21.
|
Arm III: (Placebo +Vit B6)
Patients receive placebo cream applied to palms and soles twice daily and pyridoxine as in Arm I
|
Arm IV: (Placebo + Placebo)
Patients receive placebo cream and oral placebo.
|
Arm V: Urea/Lactic Acid
Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21.
|
Arm VI: (Placebo)
Patients receive placebo cream applied to palms and soles twice daily on days 1-21.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
19
|
18
|
18
|
17
|
33
|
32
|
|
Overall Study
COMPLETED
|
18
|
18
|
16
|
16
|
31
|
28
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
2
|
1
|
2
|
4
|
Reasons for withdrawal
| Measure |
Arm I: (Urea/Lactic Acid +Vit B6)
Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily and oral pyridoxine once daily on days 1-21.
|
Arm II: (Urea/Lactic Acid + Placebo)
Patients receive topical urea/lactic acid-based cream as in arm I (closed to accrual as of 10/24/2007) and oral placebo once daily on days 1-21.
|
Arm III: (Placebo +Vit B6)
Patients receive placebo cream applied to palms and soles twice daily and pyridoxine as in Arm I
|
Arm IV: (Placebo + Placebo)
Patients receive placebo cream and oral placebo.
|
Arm V: Urea/Lactic Acid
Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21.
|
Arm VI: (Placebo)
Patients receive placebo cream applied to palms and soles twice daily on days 1-21.
|
|---|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
2
|
1
|
2
|
1
|
|
Overall Study
Protocol Violation
|
0
|
0
|
0
|
0
|
0
|
3
|
Baseline Characteristics
Pyridoxine and Topical Urea/Lactic Acid-Based Cream in Preventing Hand-Foot Syndrome in Patients Receiving Capecitabine for Breast Cancer or Other Cancer
Baseline characteristics by cohort
| Measure |
Urea/Lactic Acid Cream
n=67 Participants
Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21.
|
Placebo Cream
n=60 Participants
Patients receive placebo cream applied to palms and soles twice daily on days 1-21.
|
Total
n=127 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
<50
|
11 participants
n=5 Participants
|
9 participants
n=7 Participants
|
20 participants
n=5 Participants
|
|
Age, Customized
50-60
|
19 participants
n=5 Participants
|
17 participants
n=7 Participants
|
36 participants
n=5 Participants
|
|
Age, Customized
> 60
|
37 participants
n=5 Participants
|
34 participants
n=7 Participants
|
71 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
52 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
101 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
67 participants
n=5 Participants
|
60 participants
n=7 Participants
|
127 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: First 3 weeks of treatmentPopulation: Eight patients from the Urea/Lactic Acid group were not included in the primary analysis (1 did not fill out the diary, 1 refused treatment, 3 had adverse events before completing the diary, and 3 for other reasons). For the placebo arm, 11 were excluded (2 refused further treatment, 2 had adverse events, and 7 went off for other reasons).
A patient self-reported hand-foot syndrome (HFSD), also known as palmar-plantar erythrodysesthesia, was completed daily while applying the cream. Patients rated skin severity symptoms individually in their hands and in their feet. Definitions of symptoms, which were based on Common Terminology Criteria for Adverse Events (CTCAE) v3.0, were provided to patients. The number of patients reporting moderate to severe symptoms in either hands or feet were tabulated and percentages are reported.
Outcome measures
| Measure |
Urea/Lactic Acid Cream
n=59 Participants
Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily.
|
Placebo Cream
n=49 Participants
Patients receive placebo cream applied to palms and soles twice daily.
|
Arm III: (Placebo +Vit B6)
Patients receive placebo cream applied to palms and soles twice daily and pyridoxine as in Arm I
|
Arm IV: (Placebo + Placebo)
Patients receive placebo cream and oral placebo.
|
Arm V: Urea/Lactic Acid
Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21.
|
Arm VI: (Placebo)
Patients receive placebo cream applied to palms and soles twice daily on days 1-21.
|
|---|---|---|---|---|---|---|
|
To Determine Whether the Prophylactic Use of a Topical Urea/Lactic Acid Cream Can Decrease the Incidence/Severity of Capecitabine-caused Palmar-plantar Erythrodysesthesia
|
13.6 percentage of participants
|
10.2 percentage of participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 4, 21-day cyclesPopulation: All patients that were evaluated for adverse events were included in this analysis.
Frequency and severity of adverse events reported by patients in weekly diary and evaluated through clinical assessment by NCI CTCAE v3.0. The number of patients reporting grade 3 or higher events are reported in this outcome measure. For a full list of all events, please refer to the Adverse Events section of this report.
Outcome measures
| Measure |
Urea/Lactic Acid Cream
n=67 Participants
Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily.
|
Placebo Cream
n=63 Participants
Patients receive placebo cream applied to palms and soles twice daily.
|
Arm III: (Placebo +Vit B6)
Patients receive placebo cream applied to palms and soles twice daily and pyridoxine as in Arm I
|
Arm IV: (Placebo + Placebo)
Patients receive placebo cream and oral placebo.
|
Arm V: Urea/Lactic Acid
Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21.
|
Arm VI: (Placebo)
Patients receive placebo cream applied to palms and soles twice daily on days 1-21.
|
|---|---|---|---|---|---|---|
|
To Evaluate the Potential Toxicity of Urea/Lactic Acid Cream
Grade 3+ Adverse Event
|
21 participants
|
18 participants
|
—
|
—
|
—
|
—
|
|
To Evaluate the Potential Toxicity of Urea/Lactic Acid Cream
Grade 4+ Adverse Event
|
3 participants
|
3 participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: First 3 weeks of treatmentPopulation: This endpoint is not analyzed due to the fact that Vitamin B6 had already been shown to be ineffective. Additionally, any insignificance may be due to lack of power from the smaller (Arms I, II, III and IV) than target sample size.
A patient self-reported hand-foot syndrome diary (HFSD) was completed daily while applying the cream. Patients rated skin severity symptoms individually in their hands and in their feet. Definitions of symptoms, which were based on Common Terminology Criteria for Adverse Events (CTCAE) v3.0, were provided to patients. The number of patients reporting moderate to severe symptoms were tabulated and percentages are reported.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: up to 4, 21-day cyclesPopulation: This endpoint is not analyzed due to the fact that Vitamin B6 had already been shown to be ineffective. Additionally, any insignificance may be due to lack of power from the smaller (Arms I, II, III and IV) than target sample size.
Frequency and severity of adverse events reported by patients in weekly diary and evaluated through clinical assessment by NCI CTCAE v3.0. The number of patients reporting grade 3 or higher events are reported in this outcome measure. For a full list of all events, please refer to the Adverse Events section of this report.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: First 3 weeks of treatmentPopulation: This endpoint is not analyzed due to the fact that Vitamin B6 had already been shown to be ineffective. Additionally, any insignificance may be due to lack of power from the smaller (Arms I, II, III and IV) than target sample size.
A patient self-reported hand-foot syndrome diary (HFSD) was completed daily while applying the cream. Patients rated skin severity symptoms individually in their hands and in their feet. Definitions of symptoms, which were based on Common Terminology Criteria for Adverse Events (CTCAE) v3.0, were provided to patients. The number of patients reporting moderate to severe symptoms were tabulated.
Outcome measures
Outcome data not reported
Adverse Events
Urea/Lactic Acid Cream
Placebo Cream
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Urea/Lactic Acid Cream
n=67 participants at risk
Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21.
|
Placebo Cream
n=63 participants at risk
Patients receive placebo cream applied to palms and soles twice daily on days 1-21.
|
|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/67
|
1.6%
1/63 • Number of events 1
|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
0.00%
0/67
|
1.6%
1/63 • Number of events 1
|
|
Cardiac disorders
Arrhythmia supraventricular
|
1.5%
1/67 • Number of events 1
|
0.00%
0/63
|
|
Cardiac disorders
Atrial fibrillation
|
1.5%
1/67 • Number of events 1
|
0.00%
0/63
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/67
|
3.2%
2/63 • Number of events 2
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/67
|
3.2%
2/63 • Number of events 2
|
|
Gastrointestinal disorders
Constipation
|
1.5%
1/67 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
38.8%
26/67 • Number of events 39
|
42.9%
27/63 • Number of events 44
|
|
Gastrointestinal disorders
Ear, nose and throat examination abnormal
|
0.00%
0/67
|
1.6%
1/63 • Number of events 1
|
|
Gastrointestinal disorders
Lower gastrointestinal hemorrhage
|
0.00%
0/67
|
1.6%
1/63 • Number of events 1
|
|
Gastrointestinal disorders
Mucositis oral
|
1.5%
1/67 • Number of events 1
|
4.8%
3/63 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
6.0%
4/67 • Number of events 4
|
3.2%
2/63 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
1.5%
1/67 • Number of events 1
|
6.3%
4/63 • Number of events 4
|
|
General disorders
Chest pain
|
0.00%
0/67
|
1.6%
1/63 • Number of events 1
|
|
General disorders
Death NOS
|
1.5%
1/67 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
General disorders
Disease progression
|
1.5%
1/67 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
General disorders
Fatigue
|
6.0%
4/67 • Number of events 7
|
7.9%
5/63 • Number of events 6
|
|
General disorders
Multi-organ failure
|
1.5%
1/67 • Number of events 1
|
0.00%
0/63
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/67
|
1.6%
1/63 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/67
|
1.6%
1/63 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/67
|
3.2%
2/63 • Number of events 2
|
|
Investigations
Coagulopathy
|
0.00%
0/67
|
1.6%
1/63 • Number of events 1
|
|
Investigations
Electrocardiogram QTc interval prolonged
|
0.00%
0/67
|
1.6%
1/63 • Number of events 1
|
|
Investigations
Leukocyte count decreased
|
1.5%
1/67 • Number of events 1
|
0.00%
0/63
|
|
Investigations
Neutrophil count decreased
|
1.5%
1/67 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
Investigations
Platelet count decreased
|
1.5%
1/67 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/67
|
1.6%
1/63 • Number of events 1
|
|
Metabolism and nutrition disorders
Dehydration
|
9.0%
6/67 • Number of events 6
|
7.9%
5/63 • Number of events 6
|
|
Metabolism and nutrition disorders
Serum albumin decreased
|
0.00%
0/67
|
1.6%
1/63 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum calcium decreased
|
0.00%
0/67
|
1.6%
1/63 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum potassium decreased
|
0.00%
0/67
|
1.6%
1/63 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
1.5%
1/67 • Number of events 2
|
1.6%
1/63 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.5%
1/67 • Number of events 3
|
1.6%
1/63 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
3.0%
2/67 • Number of events 2
|
0.00%
0/63
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
1.5%
1/67 • Number of events 1
|
0.00%
0/63
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
1.5%
1/67 • Number of events 1
|
0.00%
0/63
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness upper limb
|
1.5%
1/67 • Number of events 1
|
0.00%
0/63
|
|
Nervous system disorders
Peripheral motor neuropathy
|
1.5%
1/67 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/67
|
3.2%
2/63 • Number of events 2
|
|
Psychiatric disorders
Confusion
|
3.0%
2/67 • Number of events 2
|
0.00%
0/63
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/67
|
1.6%
1/63 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
1.5%
1/67 • Number of events 1
|
1.6%
1/63 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.5%
1/67 • Number of events 1
|
1.6%
1/63 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/67
|
1.6%
1/63 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Hand-and-foot syndrome
|
64.2%
43/67 • Number of events 91
|
54.0%
34/63 • Number of events 60
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60