Breast Cancer, Drug/Agent Toxicity by Tissue/Organ, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
drug/agent toxicity by tissue/organ, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, unspecified adult solid tumor, protocol specific
Brief summary
RATIONALE: Pyridoxine (vitamin B6) and topical urea/lactic acid-based cream may prevent or lessen hand-foot syndrome caused by chemotherapy. It is not yet known whether giving pyridoxine with or without topical urea/lactic acid-based cream is more effective than topical urea/lactic acid-based cream alone or a placebo in preventing hand-foot syndrome. PURPOSE: This randomized phase III trial is studying pyridoxine and topical urea/lactic acid-based cream to see how well they work compared with giving pyridoxine together with a placebo, giving topical urea/lactic acid-based cream together with a placebo, or giving two placebos in preventing hand-foot syndrome in patients who are receiving capecitabine for breast cancer or other cancer.
Detailed description
OBJECTIVES: * Determine whether the prophylactic use of a topical urea/lactic acid cream can decrease the incidence/severity of capecitabine-caused palmar-plantar erythrodysesthesia in patients receiving capecitabine for breast and/or other cancer. * Evaluate the potential toxicity of this cream. * Determine whether the prophylactic use of vitamin B6 can decrease the incidence and/or severity of capecitabine-caused palmar-plantar erythrodysesthesia. * Evaluate the potential toxicity of vitamin B6. * Determine whether the prophylactic use of a topical urea/lactic acid cream in combination with vitamin B6 can decrease the incidence and/or severity of capecitabine caused palmar-plantar erythrodysesthesia. OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to age (\< 50 years old vs 50-60 years old vs \> 60 years old), sex, capecitabine dose level (2000 mg/day vs 2500 mg/day), cancer type (breast vs other), and mode of therapy (adjuvant \[including neo-adjuvant\] therapy vs metastatic disease). Patients are randomized to 1 of 6 treatment arms (treatment arms I-IV closed to accrual as of 10/24/007). * Arm I (closed to accrual as of 10/24/2007): 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 (closed to accrual as of 10/24/2007): 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 (closed to accrual as of 10/24/2007): Patients receive placebo cream applied to palms and soles twice daily and pyridoxine as in arm I (closed to accrual as of 10/24/2007). * Arm IV (closed to accrual as of 10/24/2007):Patients receive placebo cream as in arm III and oral placebo as in arm II (closed to accrual as of 10/24/2007). * Arm V: Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21. * Arm VI: Patients receive placebo cream applied to palms and soles twice daily on days 1-21. In all arms, treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Interventions
DIETARY_SUPPLEMENTpyridoxine hydrochloride
Given orally
DRUGurea/lactic acid-based topical cream
Applied topically
OTHERplacebo
Given orally or applied topically
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed breast and/or other cancer * Undergoing first treatment with capecitabine as adjuvant (including neo-adjuvant) therapy OR for metastatic disease * Receiving a dose of capecitabine either 2,000 mg/day (1,000 mg twice daily) OR 2,500 mg/day for 14 days with 4 courses of therapy at 3 week (+/- 3 days) intervals * Hormone-receptor status not specified PATIENT CHARACTERISTICS: * Male or female * Menopausal status not specified * No history of allergy to urea-containing cream * No pre-existing neuropathy ≥ grade 2 * No other dermatologic condition, that, in the opinion of the physician, may affect the hands or feet or may complicate evaluation during study treatment PRIOR CONCURRENT THERAPY: * No other concurrent agents that function to prevent palmar-plantar erythrodysesthesia caused by capecitabine or topical agents in the hands or feet for other indications (e.g., dryness) * No concurrent vitamin B6 \> 50 mg/day * No concurrent or planned use of over-the-counter products that contain urea or lactic acid, including any of the following: * Aqua Care® * Medicated Calamine\^® lotion (0.3%) * Coppertone\^® Waterproof Ultra Protection Sunblock * Dr. Scholl's\^® Smooth Touch deep moisturizing cream * Depicure\^® So Smooth Cream * Dove\^® Moisturizing Cream Wash * Cetaphil\^ ®Moisturizing Cream * Vaseline Intensive Care \^ ® lotion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Determine Whether the Prophylactic Use of a Topical Urea/Lactic Acid Cream Can Decrease the Incidence/Severity of Capecitabine-caused Palmar-plantar Erythrodysesthesia | First 3 weeks of treatment | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Potential Toxicity of Urea/Lactic Acid Cream | Up to 4, 21-day cycles | 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. |
| Determine Whether the Prophylactic Use of Vitamin B6 Can Decrease the Incidence and/or Severity of Capecitabine-caused Palmar-plantar Erythrodysesthesia (HFSD). | First 3 weeks of treatment | 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. |
| Evaluate the Potential Toxicity of Vitamin B6. | up to 4, 21-day cycles | 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. |
| Determine Whether the Prophylactic Use of a Topical Urea/Lactic Acid Cream in Combination With Vitamin B6 Can Decrease the Incidence and/or Severity of Capecitabine Caused Palmar-plantar Erythrodysesthesia. | First 3 weeks of treatment | 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. |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Urea/Lactic Acid Cream Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21. | 67 |
| Placebo Cream Patients receive placebo cream applied to palms and soles twice daily on days 1-21. | 60 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 2 | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | Urea/Lactic Acid Cream | Placebo Cream | Total |
|---|---|---|---|
| Age, Customized <50 | 11 participants | 9 participants | 20 participants |
| Age, Customized 50-60 | 19 participants | 17 participants | 36 participants |
| Age, Customized > 60 | 37 participants | 34 participants | 71 participants |
| Region of Enrollment United States | 67 participants | 60 participants | 127 participants |
| Sex: Female, Male Female | 52 Participants | 49 Participants | 101 Participants |
| Sex: Female, Male Male | 15 Participants | 11 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 56 / 67 | 50 / 63 |
| serious Total, serious adverse events | 0 / 67 | 0 / 63 |
Outcome results
Primary
To Determine Whether the Prophylactic Use of a Topical Urea/Lactic Acid Cream Can Decrease the Incidence/Severity of Capecitabine-caused Palmar-plantar Erythrodysesthesia
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.
Time frame: First 3 weeks of treatment
Population: 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).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Urea/Lactic Acid Cream | 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 |
| Placebo Cream | To Determine Whether the Prophylactic Use of a Topical Urea/Lactic Acid Cream Can Decrease the Incidence/Severity of Capecitabine-caused Palmar-plantar Erythrodysesthesia | 10.2 percentage of participants |
p-value: 0.768Fisher Exact
Secondary
Determine Whether the Prophylactic Use of a Topical Urea/Lactic Acid Cream in Combination With Vitamin B6 Can Decrease the Incidence and/or Severity of Capecitabine Caused Palmar-plantar Erythrodysesthesia.
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.
Time frame: First 3 weeks of treatment
Population: 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.
Secondary
Determine Whether the Prophylactic Use of Vitamin B6 Can Decrease the Incidence and/or Severity of Capecitabine-caused Palmar-plantar Erythrodysesthesia (HFSD).
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.
Time frame: First 3 weeks of treatment
Population: 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.
Secondary
Evaluate the Potential Toxicity of Vitamin B6.
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.
Time frame: up to 4, 21-day cycles
Population: 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.
Secondary
To Evaluate the Potential Toxicity of Urea/Lactic Acid Cream
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.
Time frame: Up to 4, 21-day cycles
Population: All patients that were evaluated for adverse events were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Urea/Lactic Acid Cream | To Evaluate the Potential Toxicity of Urea/Lactic Acid Cream | Grade 3+ Adverse Event | 21 participants |
| Urea/Lactic Acid Cream | To Evaluate the Potential Toxicity of Urea/Lactic Acid Cream | Grade 4+ Adverse Event | 3 participants |
| Placebo Cream | To Evaluate the Potential Toxicity of Urea/Lactic Acid Cream | Grade 3+ Adverse Event | 18 participants |
| Placebo Cream | To Evaluate the Potential Toxicity of Urea/Lactic Acid Cream | Grade 4+ Adverse Event | 3 participants |