Pyridoxine and Topical Urea/Lactic Acid-Based Cream in Preventing Hand-Foot Syndrome in Patients Receiving Capecitabine for Breast Cancer or Other Cancer

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00296036
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 137
• Locations: 231
• Arms: 6
• Patients Per Site: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Drug/Agent Toxicity by Tissue/Organ; Unspecified Adult Solid Tumor, Protocol Specific	Dietary Supplement: pyridoxine hydrochloride; Drug: urea/lactic acid-based topical cream; Other: placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 137 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: A Phase III Randomized, Placebo-controlled, Double-blind Trial to Determine the Effectiveness of a Urea/Lactic Acid-Based Topical Keratolytic Agent and Vitamin B-6 for Prevention of Capecitabine-Induced Hand and Foot Syndrome
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Dietary Supplement: pyridoxine hydrochloride; Given orally; Drug: urea/lactic acid-based topical cream; Applied topically
Experimental: 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.	Drug: urea/lactic acid-based topical cream; Applied topically; Other: placebo; Given orally or applied topically
Experimental: 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).	Dietary Supplement: pyridoxine hydrochloride; Given orally; Other: placebo; Given orally or applied topically
Placebo Comparator: 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).	Other: placebo; Given orally or applied topically
Experimental: Arm V Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21.	Drug: urea/lactic acid-based topical cream; Applied topically
Placebo Comparator: Arm VI Patients receive placebo cream applied to palms and soles twice daily on days 1-21.	Other: placebo; Given orally or applied topically

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Aurora Presbyterian Hospital	Aurora	Colorado	United States	80012
3	Boulder Community Hospital	Boulder	Colorado	United States	80301-9019
4	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado	United States	80933
5	St. Anthony Central Hospital	Denver	Colorado	United States	80204
6	Porter Adventist Hospital	Denver	Colorado	United States	80210
7	Presbyterian - St. Luke's Medical Center	Denver	Colorado	United States	80218
8	St. Joseph Hospital	Denver	Colorado	United States	80218
9	Rose Medical Center	Denver	Colorado	United States	80220
10	CCOP - Colorado Cancer Research Program	Denver	Colorado	United States	80224-2522
11	Swedish Medical Center	Englewood	Colorado	United States	80110
12	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado	United States	81502
13	North Colorado Medical Center	Greeley	Colorado	United States	80631
14	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
15	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado	United States	80502
16	McKee Medical Center	Loveland	Colorado	United States	80539
17	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado	United States	81004
18	North Suburban Medical Center	Thornton	Colorado	United States	80229
19	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
20	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida	United States	33021
21	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
22	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60504
23	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
24	Graham Hospital	Canton	Illinois	United States	61520
25	Memorial Hospital	Carthage	Illinois	United States	62321
26	Eureka Community Hospital	Eureka	Illinois	United States	61530
27	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
28	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
29	Mason District Hospital	Havana	Illinois	United States	62644
30	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
31	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
32	McDonough District Hospital	Macomb	Illinois	United States	61455
33	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois	United States	61265
34		Moline	Illinois	United States	61265
35	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
36	Community Cancer Center	Normal	Illinois	United States	61761
37	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
38	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
39	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
40	Proctor Hospital	Peoria	Illinois	United States	61614
41	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
42	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
43	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
44	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
45	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
46	Perry Memorial Hospital	Princeton	Illinois	United States	61356
47	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
48	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
49	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
50	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
51	Elkhart General Hospital	Elkhart	Indiana	United States	46515
52	Howard Community Hospital	Kokomo	Indiana	United States	46904
53	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
54	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
55	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
56	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
57	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
58	South Bend Clinic	South Bend	Indiana	United States	46617
59	McFarland Clinic, PC	Ames	Iowa	United States	50010
60		Bettendorf	Iowa	United States	52722
61	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
62	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
63	Mercy Capitol Hospital	Des Moines	Iowa	United States	50307
64	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
65	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
66	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
67	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
68	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
69	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
70	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
71	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
72	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
73	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
74	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
75	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
76	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
77	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
78	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
79	Southwest Medical Center	Liberal	Kansas	United States	67901
80	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
81	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
82	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
83	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
84	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
85	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
86	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
87	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
88	CCOP - Wichita	Wichita	Kansas	United States	67214
89	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
90	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
91	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
92	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
93	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
94	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
95	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
96	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
97	Hurley Medical Center	Flint	Michigan	United States	48503
98	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
99	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
100	Foote Memorial Hospital	Jackson	Michigan	United States	49201
101	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan	United States	48144
102	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
103	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
104	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
105	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
106	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
107	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
108	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
109	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan	United States	49085
110	St. John Macomb Hospital	Warren	Michigan	United States	48093
111	Albert Lea Cancer Center at Albert Lea Medical Center	Albert Lea	Minnesota	United States	56007
112		Alexandria	Minnesota	United States	56308
113	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
114	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
115	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
116	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
117	CCOP - Duluth	Duluth	Minnesota	United States	55805
118	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
119	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
120		Fergus Falls	Minnesota	United States	56537
121	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
122	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
123	Meeker County Memorial Hospital	Lichfield	Minnesota	United States	55355
124	Immanuel St. Joseph's	Mankato	Minnesota	United States	56002
125	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
126	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
127	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
128	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
129	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
130	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
131	CentraCare Clinic - River Campus	Saint Cloud	Minnesota	United States	56303
132	Coborn Cancer Center	Saint Cloud	Minnesota	United States	56303
133	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
134	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
135	HealthEast Cancer Care at St. Joseph's Hospital	Saint Paul	Minnesota	United States	55102
136	United Hospital	Saint Paul	Minnesota	United States	55102
137	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
138	Regions Hospital Cancer Care Center	St. Paul	Minnesota	United States	55101
139	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
140	HealthEast Cancer Care at Woodwinds Health Campus	Woodbury	Minnesota	United States	55125
141	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
142	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
143	Arch Medical Services, Incorporated at Center for Cancer Care and Research	Saint Louis	Missouri	United States	63141
144	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
145	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
146	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
147	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
148	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
149	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
150	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
151	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
152	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
153		Great Falls	Montana	United States	59405
154	Northern Montana Hospital	Havre	Montana	United States	59501
155	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
156	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
157	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
158	Community Medical Center	Missoula	Montana	United States	59801
159	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
160	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
161	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
162	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
163	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
164	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
165	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
166	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
167	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
168	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
169	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
170	MeritCare Broadway	Fargo	North Dakota	United States	58122
171	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota	United States	58201
172	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
173	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
174	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
175	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
176	CCOP - Columbus	Columbus	Ohio	United States	43215
177	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
178	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
179	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
180	Grandview Hospital	Dayton	Ohio	United States	45405
181	Good Samaritan Hospital	Dayton	Ohio	United States	45406
182	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
183	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
184	CCOP - Dayton	Dayton	Ohio	United States	45429
185	Grady Memorial Hospital	Delaware	Ohio	United States	43015
186	Hematology Oncology Center	Elyria	Ohio	United States	44035
187	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
188	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
189	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
190	Fairfield Medical Center	Lancaster	Ohio	United States	43130
191	Lima Memorial Hospital	Lima	Ohio	United States	45804
192	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
193	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537
194	St. Luke's Hospital	Maumee	Ohio	United States	43537
195	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
196	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
197	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
198	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
199	Mercy Medical Center	Springfield	Ohio	United States	45504
200	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
201	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
202	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
203	Toledo Hospital	Toledo	Ohio	United States	43606
204	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
205	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
206	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
207	St. Anne Mercy Hospital	Toledo	Ohio	United States	43623
208	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
209	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
210	Fulton County Health Center	Wauseon	Ohio	United States	43567
211	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
212	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
213	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
214	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
215	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma	United States	74136
216	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania	United States	18105
217	AnMed Cancer Center	Anderson	South Carolina	United States	29621
218	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
219	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
220	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
221	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
222	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
223	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
224	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
225	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
226	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
227	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
228	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
229	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
230	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
231	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Charles L. Loprinzi, MD, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00296036
• Other Study ID Numbers: NCCTG-N05C5; NCI-2009-00655; ROCHE-NCCTG-N05C5; CDR0000464246
• First Posted: Feb 24, 2006
• Last Update Posted: Mar 16, 2017
• Last Verified: Jan 1, 2017

• Keywords provided by Alliance for Clinical Trials in Oncology: 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
• Additional relevant MeSH terms: Breast Neoplasms; Drug-Related Side Effects and Adverse Reactions; Pyridoxine; Vitamin B 6

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Arm I: (Urea/Lactic Acid +Vit B6)	Arm II: (Urea/Lactic Acid + Placebo)	Arm III: (Placebo +Vit B6)	Arm IV: (Placebo + Placebo)	Arm V: Urea/Lactic Acid	Arm VI: (Placebo)
Arm/Group Description	Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily and oral pyridoxine once daily on days 1-21.	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.	Patients receive placebo cream applied to palms and soles twice daily and pyridoxine as in Arm I	Patients receive placebo cream and oral placebo.	Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21.	Patients receive placebo cream applied to palms and soles twice daily on days 1-21.
Period Title: Overall Study
STARTED	19	18	18	17	33	32
COMPLETED	18	18	16	16	31	28
NOT COMPLETED	1	0	2	1	2	4

Baseline Characteristics

Arm/Group Title	Urea/Lactic Acid Cream	Placebo Cream	Total
Arm/Group Description	Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21.	Patients receive placebo cream applied to palms and soles twice daily on days 1-21.	Total of all reporting groups
Overall Participants	67	60	127
Age, Customized (participants) [Number]
<50	11 16.4%	9 15%	20 15.7%
50-60	19 28.4%	17 28.3%	36 28.3%
> 60	37 55.2%	34 56.7%	71 55.9%
Sex: Female, Male (Count of Participants)
Female	52 77.6%	49 81.7%	101 79.5%
Male	15 22.4%	11 18.3%	26 20.5%
Region of Enrollment (participants) [Number]
United States	67 100%	60 100%	127 100%

Outcome Measures

1. Primary Outcome

Title	To Determine Whether the Prophylactic Use of a Topical Urea/Lactic Acid Cream Can Decrease the Incidence/Severity of Capecitabine-caused Palmar-plantar Erythrodysesthesia
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Urea/Lactic Acid Cream	Placebo Cream
Arm/Group Description	Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily.	Patients receive placebo cream applied to palms and soles twice daily.
Measure Participants	59	49
Number [percentage of participants]	13.6 20.3%	10.2 17%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Urea/Lactic Acid Cream, Placebo Cream
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.768
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	To Evaluate the Potential Toxicity of Urea/Lactic Acid Cream
Description	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

Outcome Measure Data

Analysis Population Description

All patients that were evaluated for adverse events were included in this analysis.

Arm/Group Title	Urea/Lactic Acid Cream	Placebo Cream
Arm/Group Description	Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily.	Patients receive placebo cream applied to palms and soles twice daily.
Measure Participants	67	63
Grade 3+ Adverse Event	21 31.3%	18 30%
Grade 4+ Adverse Event	3 4.5%	3 5%

3. Secondary Outcome

Title	Determine Whether the Prophylactic Use of Vitamin B6 Can Decrease the Incidence and/or Severity of Capecitabine-caused Palmar-plantar Erythrodysesthesia (HFSD).
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm I: (Urea/Lactic Acid +Vit B6)	Arm II: (Urea/Lactic Acid + Placebo)	Arm III: (Placebo +Vit B6)	Arm IV: (Placebo + Placebo)	Arm V: Urea/Lactic Acid	Arm VI: (Placebo)
Arm/Group Description	Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily and oral pyridoxine once daily on days 1-21.	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.	Patients receive placebo cream applied to palms and soles twice daily and pyridoxine as in Arm I	Patients receive placebo cream and oral placebo.	Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21.	Patients receive placebo cream applied to palms and soles twice daily on days 1-21.
Measure Participants	0	0	0	0	0	0

4. Secondary Outcome

Title	Evaluate the Potential Toxicity of Vitamin B6.
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm I: (Urea/Lactic Acid +Vit B6)	Arm II: (Urea/Lactic Acid + Placebo)	Arm III: (Placebo +Vit B6)	Arm IV: (Placebo + Placebo)	Arm V: Urea/Lactic Acid	Arm VI: (Placebo)
Arm/Group Description	Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily and oral pyridoxine once daily on days 1-21.	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.	Patients receive placebo cream applied to palms and soles twice daily and pyridoxine as in arm I.	Patients receive placebo cream as in arm III and oral placebo as in arm II.	Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21.	Patients receive placebo cream applied to palms and soles twice daily on days 1-21.
Measure Participants	0	0	0	0	0	0

5. Secondary Outcome

Title	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.
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm I: (Urea/Lactic Acid +Vit B6)	Arm II: (Urea/Lactic Acid + Placebo)	Arm III: (Placebo +Vit B6)	Arm IV: (Placebo + Placebo)	Arm V: Urea/Lactic Acid	Arm VI: (Placebo)
Arm/Group Description	Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily and oral pyridoxine once daily on days 1-21.	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. urea/lactic acid-based topical cream: Applied topically placebo: Given orally or applied topically	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).	Patients receive placebo cream as in arm III and oral placebo as in arm II (closed to accrual as of 10/24/2007).	Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21.	Patients receive placebo cream applied to palms and soles twice daily on days 1-21.
Measure Participants	0	0	0	0	0	0

Adverse Events

Arm/Group Title	Urea/Lactic Acid Cream		Placebo Cream
Arm/Group Description	Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily on days 1-21.		Patients receive placebo cream applied to palms and soles twice daily on days 1-21.
All Cause Mortality
	Urea/Lactic Acid Cream		Placebo Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Urea/Lactic Acid Cream		Placebo Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/67 (0%)		0/63 (0%)
Other (Not Including Serious) Adverse Events
	Urea/Lactic Acid Cream		Placebo Cream
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	56/67 (83.6%)		50/63 (79.4%)
Blood and lymphatic system disorders
Febrile neutropenia	0/67 (0%)	0	1/63 (1.6%)	1
Hemoglobin decreased	0/67 (0%)	0	1/63 (1.6%)	1
Cardiac disorders
Arrhythmia supraventricular	1/67 (1.5%)	1	0/63 (0%)	0
Atrial fibrillation	1/67 (1.5%)	1	0/63 (0%)	0
Gastrointestinal disorders
Abdominal distension	0/67 (0%)	0	2/63 (3.2%)	2
Ascites	0/67 (0%)	0	2/63 (3.2%)	2
Constipation	1/67 (1.5%)	1	1/63 (1.6%)	1
Diarrhea	26/67 (38.8%)	39	27/63 (42.9%)	44
Ear, nose and throat examination abnormal	0/67 (0%)	0	1/63 (1.6%)	1
Lower gastrointestinal hemorrhage	0/67 (0%)	0	1/63 (1.6%)	1
Mucositis oral	1/67 (1.5%)	1	3/63 (4.8%)	3
Nausea	4/67 (6%)	4	2/63 (3.2%)	2
Vomiting	1/67 (1.5%)	1	4/63 (6.3%)	4
General disorders
Chest pain	0/67 (0%)	0	1/63 (1.6%)	1
Death NOS	1/67 (1.5%)	1	1/63 (1.6%)	1
Disease progression	1/67 (1.5%)	1	1/63 (1.6%)	1
Fatigue	4/67 (6%)	7	5/63 (7.9%)	6
Multi-organ failure	1/67 (1.5%)	1	0/63 (0%)	0
Infections and infestations
Pharyngitis	0/67 (0%)	0	1/63 (1.6%)	1
Investigations
Alanine aminotransferase increased	0/67 (0%)	0	1/63 (1.6%)	1
Aspartate aminotransferase increased	0/67 (0%)	0	2/63 (3.2%)	2
Coagulopathy	0/67 (0%)	0	1/63 (1.6%)	1
Electrocardiogram QTc interval prolonged	0/67 (0%)	0	1/63 (1.6%)	1
Leukocyte count decreased	1/67 (1.5%)	1	0/63 (0%)	0
Neutrophil count decreased	1/67 (1.5%)	1	1/63 (1.6%)	1
Platelet count decreased	1/67 (1.5%)	1	1/63 (1.6%)	1
Metabolism and nutrition disorders
Anorexia	0/67 (0%)	0	1/63 (1.6%)	1
Dehydration	6/67 (9%)	6	5/63 (7.9%)	6
Serum albumin decreased	0/67 (0%)	0	1/63 (1.6%)	1
Serum calcium decreased	0/67 (0%)	0	1/63 (1.6%)	1
Serum potassium decreased	0/67 (0%)	0	1/63 (1.6%)	1
Serum sodium decreased	1/67 (1.5%)	2	1/63 (1.6%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/67 (1.5%)	3	1/63 (1.6%)	3
Bone pain	2/67 (3%)	2	0/63 (0%)	0
Muscle weakness	1/67 (1.5%)	1	0/63 (0%)	0
Muscle weakness lower limb	1/67 (1.5%)	1	0/63 (0%)	0
Muscle weakness upper limb	1/67 (1.5%)	1	0/63 (0%)	0
Nervous system disorders
Peripheral motor neuropathy	1/67 (1.5%)	1	1/63 (1.6%)	1
Peripheral sensory neuropathy	0/67 (0%)	0	2/63 (3.2%)	2
Psychiatric disorders
Confusion	2/67 (3%)	2	0/63 (0%)	0
Renal and urinary disorders
Urinary incontinence	0/67 (0%)	0	1/63 (1.6%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/67 (1.5%)	1	1/63 (1.6%)	2
Pleural effusion	1/67 (1.5%)	1	1/63 (1.6%)	1
Skin and subcutaneous tissue disorders
Alopecia	0/67 (0%)	0	1/63 (1.6%)	1
Hand-and-foot syndrome	43/67 (64.2%)	91	34/63 (54%)	60

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.