Baclofen-Amitriptyline Hydrochloride-Ketamine Gel in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00516503
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 208
• Locations: 165
• Arms: 2
• Duration (Months): 23
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Baclofen-amitriptyline-ketamine (BAK) gel may lessen peripheral neuropathy caused by chemotherapy. It is not yet known whether BAK gel is more effective than a placebo in treating peripheral neuropathy caused by chemotherapy .

PURPOSE: This randomized phase III trial is studying BAK gel to see how well it works compared with a placebo in treating peripheral neuropathy caused by chemotherapy in patients with cancer.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neurotoxicity; Pain; Unspecified Adult Solid Tumor, Protocol Specific	Drug: baclofen/amitriptyline/ketamine gel; Other: placebo	Phase 3

Detailed Description

OBJECTIVES Primary

• Compare the effectiveness of baclofen-amitriptyline hydrochloride-ketamine (BAK) gel versus placebo, in terms of improving sensory neuropathy, in cancer patients with chemotherapy-induced peripheral neuropathy> Secondary>

• Compare motor and autonomic symptoms and functioning, mood states, pain, and peripheral neuropathy in these patients.

• Assess the adverse event profile of topical BAK gel.

• Explore whether topical BAK gel is absorbed systemically. OUTLINE: Patients are stratified according to neurotoxic chemotherapy (active vs non-active), current use of opioids or oral pain medications (yes vs no), pain rating (4-7 vs 8-10), and prior ineffective pharmacologic treatment for peripheral neuropathy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks.

• Arm II: Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks.

Some patients in both arms may choose to continue on the active gel or, if on placebo, begin the active gel for an additional 8 weeks off study. Patients complete health, pain, mood, and quality of life questionnaires at baseline and periodically during study. Patients also record adverse symptoms weekly in a Symptom Experience Diary.

Study Design

• Study Type: Interventional
• Actual Enrollment: 208 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: The Use of Topical Baclofen, Amitriptyline HCI, and Ketamine (BAK) in a PLO Gel vs. Placebo for the Treatment of Chemotherapy Induced Peripheral Neuropathy: A Phase III Randomized Double-Blind Placebo Controlled Study
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel> topically to each> area of pain,> numbness,> and/or tingling> on the> feet and/or hands twice daily> for> 4 weeks.	Drug: baclofen/amitriptyline/ketamine gel; Applied topically
Placebo Comparator: Arm II Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks.	Other: placebo; Applied topically

Outcome Measures

Primary Outcome Measures

1. Total Sensory Neuropathy as Measured by the European Organization for Research and Treatment of Cancer [EORTC] Quality of Life [QLQ] - Chemo-induced Peripheral Neuropathy [CIPN20] [From baseline to 4 weeks]

   The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The primary analysis was the change in sensory neuropathy subscale of the CIPN-20 from baseline to week 4. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's sensory neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.

Secondary Outcome Measures

1. Motor Neuropathy as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4 [From Baseline to week 4]

   The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The secondary analysis was to compare changes from baseline at 4 weeks for the motor neuropathy subscale of the CIPN-20. To analyze this endpoint, the area under the curve (AUC) from baseline to week 4 was calculated for each patient's motor neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.

2. Autonomic Symptoms and Functioning as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4 [Up to 4 weeks]

   The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The secondary analysis was to compare changes from baseline at 4 weeks for the autonomic neuropathy subscale of the CIPN-20. To analyze this endpoint, the area under the curve (AUC) from baseline to week 4 was calculated for each patient's motor neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.

3. Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS) [At 4 weeks]

   Each mood scale (0 - 100, higher is better mood) will be analyzed as an endpoint along with the total mood disturbance score.

4. Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4 [Up to 4 weeks]

   Pain severity, defined by the four items addressing worst, least, and average pain and pain right now as measured by the BPI will be analyzed identical to the primary endpoint. Additionally, total pain interference as measured by the BPI will be transformed onto a 0-100 ( higher is less pain) point scale. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's score. The average AUC for the placebo arm and the topical amitriptyline HCl/ baclofen/ ketamine arm are reported.

5. Numbness, Tingling, and Pain as Measured by the Peripheral Neuropathy Questionnaire at Baseline and Weekly for 4 Weeks [Up to 4 weeks]

   The Peripheral Neuropathy Questionnaire was used to analyze this endpoint. Patient neuropathy symptoms were scored on a 0 - 100 scale (higher score represents less symptomatic). The area under the curve (AUC) from baseline to week 4 was calculated for each patient's score. The average AUC for the placebo arm and the topical amitriptyline HCl/ baclofen/ ketamine arm are reported.

6. Adverse Event Profile of Topical Amitriptyline HCl/ Baclofen/Ketamine > Frequency and Severity of Adverse Events Reported by the Patient in the > Symptom Experience Diary and Evaluated Through Clinical Assessment by NCI CTCAE v3.0 [Up to 4 weeks]

   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.

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:>

• Diagnosis of cancer>

• Received or currently receiving neurotoxic chemotherapy including, but not limited to, taxanes (e.g., paclitaxel or docetaxel); platinum-based compounds (e.g., carboplatin, cisplatin, or oxaliplatin); vinca alkaloids (e.g., vincristine or vinblastine); or other neurotoxic chemotherapy agents (e.g., bortezomib, lenalidomide, or thalidomide)>

• Must have pain or symptoms of peripheral neuropathy attributable to chemotherapy for ≥ 1 month>

• Neuropathy is limited to either hands and/or feet where gel can be applied>

• Neuropathic pain score of ≥ 4 out of 10 on the numbness/tingling/pain numeric analogue scale>

• No pre-existing or history of peripheral neuropathy due to any cause other than chemotherapy (e.g., diabetes, alcohol, toxin, heredity)> PATIENT CHARACTERISTICS:>

• ECOG performance status 0-2>

• Life expectancy ≥ 4 months>

• Creatinine ≤ 1.5 times upper limit of normal>

• Not pregnant or nursing>

• No ability to bear children defined by 1 of the criteria:>

• Menopausal (12 months and no menstrual period if natural menopause)>

• Underwent a hysterectomy and/or oophorectomy>

• Permanent surgical sterilization (tubal ligation)>

• Fertile patients must use effective contraception>

• Able to complete questionnaires independently or with assistance>

• Able to sign informed consent and understand the nature of a placebo-controlled trial>

• No history of an allergic reaction to baclofen, amitriptyline hydrochloride, and/or ketamine>

• No diagnosis of any New York Heart Association class I-IV congestive heart failure>

• No diagnosis of coronary artery disease including, but not limited to, myocardial infarction, within the past 5 years>

• No other medical condition that, in the opinion of the treating physician or allied health professional, would make this clinical trial unreasonably hazardous for the patient>

• No skin abnormalities at the intended application sites (hands and feet) of study gel (i.e., skin breakdown)> PRIOR CONCURRENT THERAPY:>

• See Disease Characteristics>

• More than 30 days since prior anticonvulsants, tricyclic antidepressants, monoamine oxidase inhibitor, or other neuropathic pain medication (e.g., carbamazepine, phenytoin, valproic acid, gabapentin, lamotrigine, topical lidocaine patch or gel, capsaicin cream, or amifostine)>

• Patients treated with any of these agents for peripheral neuropathy for ≤ 1 week during the past 30 days are eligible provided they are no longer taking the agent>

• More than 5 years since prior percutaneous transluminal coronary angioplasty or coronary artery bypass graft>

• Prior heart valve replacement surgery allowed provided patient has fully recovered from the surgery>

• No concurrent use of study agents other than as specified in the trial>

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Scottsdale	Scottsdale	Arizona	United States	85259-5499
2	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
3	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60504
4	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
5	Graham Hospital	Canton	Illinois	United States	61520
6	Memorial Hospital	Carthage	Illinois	United States	62321
7	Eureka Community Hospital	Eureka	Illinois	United States	61530
8	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
9	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
10	Mason District Hospital	Havana	Illinois	United States	62644
11	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
12	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
13	McDonough District Hospital	Macomb	Illinois	United States	61455
14		Moline	Illinois	United States	61265
15	Community Cancer Center	Normal	Illinois	United States	61761
16	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
17	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
18	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
19	Proctor Hospital	Peoria	Illinois	United States	61614
20	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
21	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
22	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
23	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
24	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
25	Perry Memorial Hospital	Princeton	Illinois	United States	61356
26	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
27	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
28	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
29	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
30	Elkhart General Hospital	Elkhart	Indiana	United States	46515
31	Howard Community Hospital	Kokomo	Indiana	United States	46904
32	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
33	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
34	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
35	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
36	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
37	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
38	McFarland Clinic, PC	Ames	Iowa	United States	50010
39		Bettendorf	Iowa	United States	52722
40	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
41	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
42	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
43	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
44	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
45	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan	United States	48144
46	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
47	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
48	Lakeland Regional Cancer Care Center - St. Joseph	Saint Joseph	Michigan	United States	49085
49	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
50	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
51	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
52	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
53	CCOP - Duluth	Duluth	Minnesota	United States	55805
54	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
55	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
56	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
57	Immanuel St. Joseph's	Mankato	Minnesota	United States	56002
58	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
59	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
60	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
61	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
62	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
63	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
64	United Hospital	Saint Paul	Minnesota	United States	55102
65	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
66	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota	United States	56201
67	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
68	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
69	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
70	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
71	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
72	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
73	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
74	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
75	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
76	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
77		Great Falls	Montana	United States	59405
78	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
79	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
80	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
81	Community Medical Center	Missoula	Montana	United States	59801
82	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
83	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
84	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
85	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
86	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
87	Immanuel Medical Center	Omaha	Nebraska	United States	68122
88	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
89	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
90	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
91	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
92	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
93	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
94	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
95	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
96	MeritCare Broadway	Fargo	North Dakota	United States	58122
97	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota	United States	58201
98	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
99	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
100	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
101	North Coast Cancer Care - Clyde	Clyde	Ohio	United States	43410
102	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
103	CCOP - Columbus	Columbus	Ohio	United States	43215
104	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
105	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
106	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
107	Grandview Hospital	Dayton	Ohio	United States	45405
108	Good Samaritan Hospital	Dayton	Ohio	United States	45406
109	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
110	CCOP - Dayton	Dayton	Ohio	United States	45429
111	Grady Memorial Hospital	Delaware	Ohio	United States	43015
112	Hematology Oncology Center	Elyria	Ohio	United States	44035
113	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
114	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
115	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
116	Fairfield Medical Center	Lancaster	Ohio	United States	43130
117	Lima Memorial Hospital	Lima	Ohio	United States	45804
118	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
119	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537
120	St. Luke's Hospital	Maumee	Ohio	United States	43537
121	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
122	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
123	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
124	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
125	Mercy Medical Center	Springfield	Ohio	United States	45504
126	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
127	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
128	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
129	Toledo Hospital	Toledo	Ohio	United States	43606
130	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
131	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
132	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
133	St. Anne Mercy Hospital	Toledo	Ohio	United States	43623
134	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
135	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
136	Fulton County Health Center	Wauseon	Ohio	United States	43567
137	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
138	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
139	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
140	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
141	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
142	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
143	Legacy Good Samaritan Hospital & Comprehensive Cancer Center	Portland	Oregon	United States	97210
144	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon	United States	97213-2967
145	Adventist Medical Center	Portland	Oregon	United States	97216
146	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
147	Providence St. Vincent Medical Center	Portland	Oregon	United States	97225
148	Legacy Emanuel Hospital and Health Center and Children's Hospital	Portland	Oregon	United States	97227
149	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
150	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
151	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania	United States	18201
152	Guthrie Cancer Center at Guthrie Clinic Sayre	Sayre	Pennsylvania	United States	18840
153	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
154	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
155	Mercy Hospital at Wilkes-Barre	Wilkes-Barre	Pennsylvania	United States	18765
156	AnMed Cancer Center	Anderson	South Carolina	United States	29621
157	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
158	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
159	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
160	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
161	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
162	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
163	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
164	Southwest Washington Medical Center Cancer Center	Vancouver	Washington	United States	98668
165	Franciscan Skemp Healthcare - La Crosse Campus	La Crosse	Wisconsin	United States	54601

Sponsors and Collaborators

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

Investigators

• Study Chair: Debra Barton, RN, PhD, AOCN, FAAN, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00516503
• Other Study ID Numbers: NCCTG-N06CA; NCI-2011-01768; CDR0000560732
• First Posted: Aug 15, 2007
• Last Update Posted: Aug 24, 2017
• Last Verified: Jul 1, 2017

• Additional relevant MeSH terms: Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma; Peripheral Nervous System Diseases; Myelodysplastic Syndromes; Myeloproliferative Disorders; Lymphoproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Disease; Ketamine; Amitriptyline; Baclofen

Study Results

Participant Flow

Pre-assignment Detail	Two-hundred eight patients were enrolled to this study. Five patients cancelled prior to initiating protocol treatment and were therefore this study was analyzed using 203 remaining patients.

Arm/Group Title	Baclofen-amitriptyline Hydrochloride-ketamine	Placebo
Arm/Group Description	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
Period Title: Overall Study
STARTED	101	102
COMPLETED	101	102
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Baclofen-amitriptyline Hydrochloride-ketamine	Placebo	Total
Arm/Group Description	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically	Total of all reporting groups
Overall Participants	101	102	203
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59.5	62	61
Sex: Female, Male (Count of Participants)
Female	66 65.3%	60 58.8%	126 62.1%
Male	35 34.7%	42 41.2%	77 37.9%
Region of Enrollment (participants) [Number]
United States	101 100%	102 100%	203 100%

Outcome Measures

1. Primary Outcome

Title	Total Sensory Neuropathy as Measured by the European Organization for Research and Treatment of Cancer [EORTC] Quality of Life [QLQ] - Chemo-induced Peripheral Neuropathy [CIPN20]
Description	The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The primary analysis was the change in sensory neuropathy subscale of the CIPN-20 from baseline to week 4. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's sensory neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.
Time Frame	From baseline to 4 weeks

Outcome Measure Data

Analysis Population Description

There were 26 participants in the BAK arm and 27 in the placebo arm who did not provide primary endpoint data. In the BAK arm, 11 refused due to experiencing an adverse event and 15 refused for non-specified reasons. In the placebo arm, eight refused due to an adverse event, one patient died, and 18 refused for non-specified reasons.

Arm/Group Title	Baclofen-amitriptyline Hydrochloride-ketamine	Placebo
Arm/Group Description	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
Measure Participants	75	75
Mean (Standard Deviation) [(units on a scale) * week]	61.0 (16.22)	60.9 (17.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baclofen-amitriptyline Hydrochloride-ketamine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.90
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Motor Neuropathy as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4
Description	The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The secondary analysis was to compare changes from baseline at 4 weeks for the motor neuropathy subscale of the CIPN-20. To analyze this endpoint, the area under the curve (AUC) from baseline to week 4 was calculated for each patient's motor neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.
Time Frame	From Baseline to week 4

Outcome Measure Data

Analysis Population Description

There were 26 participants in the BAK arm and 27 in the placebo arm who did not provide primary endpoint data. In the BAK arm, 11 refused due to experiencing an adverse> event and 15 refused for non-specified reasons. In the placebo arm, eight refused due to an> adverse event, one patient died, and 18 refused for non-specified reasons.

Arm/Group Title	Baclofen-amitriptyline Hydrochloride-ketamine	Placebo
Arm/Group Description	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
Measure Participants	75	75
Mean (Standard Deviation) [(units on a scale)* week]	69.2 (17.15)	70.1 (19.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baclofen-amitriptyline Hydrochloride-ketamine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.50
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Autonomic Symptoms and Functioning as Measured by the EORTC QLQ-CIPN20 at Baseline and Week 4
Description	The scoring algorithm for the parent instrument, the EORTC QLQ-C30, was applied for linearly converting items and subscales of CIPN-20 to 0-100 scales so that a high score corresponds to better condition or less symptom. The secondary analysis was to compare changes from baseline at 4 weeks for the autonomic neuropathy subscale of the CIPN-20. To analyze this endpoint, the area under the curve (AUC) from baseline to week 4 was calculated for each patient's motor neuropathy score. The average AUC for the placebo arm was compared to the average AUC for the topical amitriptyline HCl/ baclofen/ ketamine arm using a Wilcoxon rank sum test.
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

There were 26 participants in the BAK arm and 27 in the placebo arm who did not provide primary endpoint data. In the BAK arm, 11 refused due to experiencing an adverse event and 15 refused for non-specified reasons. In the placebo arm, eight refused due to an adverse event, one patient died, and 18 refused for non-specified reasons.

Arm/Group Title	Baclofen-amitriptyline Hydrochloride-ketamine	Placebo
Arm/Group Description	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
Measure Participants	75	75
Mean (Standard Deviation) [(units on a scale)*week]	85.0 (15.47)	86.8 (15.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Baclofen-amitriptyline Hydrochloride-ketamine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.50
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Mood States and Total Mood Disturbance as Measured by the Profile of Mood States (POMS)
Description	Each mood scale (0 - 100, higher is better mood) will be analyzed as an endpoint along with the total mood disturbance score.
Time Frame	At 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen-amitriptyline Hydrochloride-ketamine	Placebo
Arm/Group Description	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
Measure Participants	101	102
POMS Tension-Anxiety Subscale	83.2 (17.09)	83.0 (15.73)
POMS VA Subscale	31.1 (18.42)	33.0 (19.61)
POMS Anger-Hostility Score	87.8 (14.48)	87.7 (12.98)
POMS Confusion-Bewilderment	76.9 (17.58)	77.9 (11.75)
POMS Depression-Dejection Score	86.4 (16.09)	85.8 (15.23)
POMS Fatigue-Inertia Score	67.2 (21.69)	63.6 (22.22)
Mean POMS Score	71.5 (13.27)	71.8 (13.14)

5. Secondary Outcome

Title	Pain Severity and Interference as Measured by the Brief Pain Inventory (BPI) at Baseline and Week 4
Description	Pain severity, defined by the four items addressing worst, least, and average pain and pain right now as measured by the BPI will be analyzed identical to the primary endpoint. Additionally, total pain interference as measured by the BPI will be transformed onto a 0-100 ( higher is less pain) point scale. The area under the curve (AUC) from baseline to week 4 was calculated for each patient's score. The average AUC for the placebo arm and the topical amitriptyline HCl/ baclofen/ ketamine arm are reported.
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen-amitriptyline Hydrochloride-ketamine	Placebo
Arm/Group Description	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
Measure Participants	101	102
Worst Pain	58.1 (25.48)	58.7 (27.39)
Least Pain	78.0 (20.28)	77.3 (22.01)
Average Pain	66.4 (21.99)	65.4 (24.55)
BPI Total Interference	76.5 (20.16)	77.3 (21.16)

6. Secondary Outcome

Title	Numbness, Tingling, and Pain as Measured by the Peripheral Neuropathy Questionnaire at Baseline and Weekly for 4 Weeks
Description	The Peripheral Neuropathy Questionnaire was used to analyze this endpoint. Patient neuropathy symptoms were scored on a 0 - 100 scale (higher score represents less symptomatic). The area under the curve (AUC) from baseline to week 4 was calculated for each patient's score. The average AUC for the placebo arm and the topical amitriptyline HCl/ baclofen/ ketamine arm are reported.
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Baclofen-amitriptyline Hydrochloride-ketamine	Placebo
Arm/Group Description	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
Measure Participants	101	102
Mean (Standard Deviation) [units on a scale * week]	172.6 (82.09)	175.7 (85.38)

7. Secondary Outcome

Title	Adverse Event Profile of Topical Amitriptyline HCl/ Baclofen/Ketamine > Frequency and Severity of Adverse Events Reported by the Patient in the > Symptom Experience Diary and Evaluated Through Clinical Assessment by NCI CTCAE v3.0
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 weeks

Outcome Measure Data

Analysis Population Description

All patients that were assessed for adverse events are used in this analysis.

Arm/Group Title	Baclofen-amitriptyline Hydrochloride-ketamine	Placebo
Arm/Group Description	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.	Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
Measure Participants	101	102
Grade 3+ Adverse Event	8 7.9%	5 4.9%
Grade 4+ Adverse Event	1 1%	1 1%

Adverse Events

Arm/Group Title	Baclofen-amitriptyline Hydrochloride-ketamine		Placebo
Arm/Group Description	Patients apply 1 spoonful of baclofen-amitriptyline hydrochloride-ketamine gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Baclofen/amitriptyline/ketamine gel: Applied topically.		Patients apply 1 spoonful of placebo gel topically to each area of pain, numbness, and/or tingling on the feet and/or hands twice daily for 4 weeks. Placebo: Applied topically
All Cause Mortality
	Baclofen-amitriptyline Hydrochloride-ketamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Baclofen-amitriptyline Hydrochloride-ketamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/101 (1%)		1/102 (1%)
General disorders
Disease progression	0/101 (0%)	0	1/102 (1%)	1
Vascular disorders
Thrombosis	1/101 (1%)	1	0/102 (0%)	0
Other (Not Including Serious) Adverse Events
	Baclofen-amitriptyline Hydrochloride-ketamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/101 (47.5%)		45/102 (44.1%)
Ear and labyrinth disorders
Tinnitus	0/101 (0%)	0	1/102 (1%)	1
Gastrointestinal disorders
Abdominal pain	0/101 (0%)	0	2/102 (2%)	5
Constipation	24/101 (23.8%)	62	28/102 (27.5%)	71
Diarrhea	1/101 (1%)	1	1/102 (1%)	1
Dry mouth	18/101 (17.8%)	55	23/102 (22.5%)	55
Ileal obstruction	0/101 (0%)	0	1/102 (1%)	1
Nausea	1/101 (1%)	1	0/102 (0%)	0
Small intestinal obstruction	0/101 (0%)	0	2/102 (2%)	4
Stomach pain	0/101 (0%)	0	0/102 (0%)	0
Vomiting	1/101 (1%)	1	0/102 (0%)	0
General disorders
Edema limbs	1/101 (1%)	1	1/102 (1%)	1
Fatigue	1/101 (1%)	1	1/102 (1%)	1
Pain	0/101 (0%)	0	0/102 (0%)	0
Immune system disorders
Hypersensitivity	0/101 (0%)	0	1/102 (1%)	1
Infections and infestations
Bladder infection	0/101 (0%)	0	0/102 (0%)	0
Skin infection	1/101 (1%)	2	0/102 (0%)	0
Injury, poisoning and procedural complications
Fracture	0/101 (0%)	0	0/102 (0%)	0
Investigations
Alkaline phosphatase increased	0/101 (0%)	0	1/102 (1%)	1
Aspartate aminotransferase increased	0/101 (0%)	0	1/102 (1%)	1
Platelet count decreased	0/101 (0%)	0	1/102 (1%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/101 (0%)	0	0/102 (0%)	0
Chest wall pain	0/101 (0%)	0	0/102 (0%)	0
Joint pain	1/101 (1%)	1	0/102 (0%)	0
Pain in extremity	1/101 (1%)	1	0/102 (0%)	0
Nervous system disorders
Ataxia	0/101 (0%)	0	1/102 (1%)	1
Depressed level of consciousness	2/101 (2%)	2	2/102 (2%)	2
Dizziness	0/101 (0%)	0	0/102 (0%)	0
Neuralgia	1/101 (1%)	1	0/102 (0%)	0
Peripheral sensory neuropathy	0/101 (0%)	0	2/102 (2%)	2
Syncope vasovagal	0/101 (0%)	0	0/102 (0%)	0
Psychiatric disorders
Anxiety	0/101 (0%)	0	0/102 (0%)	0
Confusion	5/101 (5%)	5	4/102 (3.9%)	4
Skin and subcutaneous tissue disorders
Dry skin	1/101 (1%)	1	0/102 (0%)	0
Hand-and-foot syndrome	16/101 (15.8%)	26	12/102 (11.8%)	25
Pruritus	0/101 (0%)	0	0/102 (0%)	0
Vascular disorders
Thrombosis	0/101 (0%)	0	1/102 (1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.