Duloxetine 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: NCT00489411
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 231
• Locations: 475
• Arms: 2
• Duration (Months): 59
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Duloxetine may lessen peripheral neuropathy caused by chemotherapy. It is not yet known whether duloxetine is more effective than a placebo in treating peripheral neuropathy caused by chemotherapy.

PURPOSE: This randomized phase III trial is studying duloxetine 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
Neurotoxicity; Pain; Peripheral Neuropathy; Unspecified Adult Solid Tumor, Protocol Specific	Drug: duloxetine hydrochloride; Other: placebo	Phase 3

Detailed Description

OBJECTIVES:

Primary

• Determine the efficacy of duloxetine hydrochloride in cancer patients with painful chemotherapy-induced (taxane or platinum agent) peripheral neuropathy.

Secondary

• Determine the influence of this drug on peripheral neuropathy-related functional status and quality of life of these patients.

• Describe the differences in duloxetine hydrochloride efficacy when used to treat pain caused by chemotherapy-induced peripheral neuropathy based on the neurotoxic drug and class.

OUTLINE: This is a randomized, double-blind, placebo-controlled, crossover study. Patients are stratified according to prior neurotoxic agent (paclitaxel vs oxaliplatin vs other taxane agents without paclitaxel vs platinum agents [cisplatin] without oxaliplatin) and high risk for developing painful chemotherapy-induced peripheral neuropathy (no vs yes). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral duloxetine hydrochloride once or twice daily in weeks 1-6. After a 1-week rest period, patients cross over to receive an oral placebo once or twice daily in weeks 8-13.

• Arm II: Patients receive an oral placebo once or twice daily in weeks 1-6. After a 1-week rest period, patients cross over to receive oral duloxetine hydrochloride once or twice daily in weeks 8-13.

Patients complete pain and quality of life questionnaires, including the BPI-SF once weekly and FACT/GOG-NTX and EORTC QLQ-C30 questionnaires, in weeks 1, 6, 8, and 13.

After completion of study treatment, patients are followed for 2 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 231 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: A Phase III Double Blind Trial of Oral Duloxetine for Treatment of Pain Associated With Chemotherapy-Induced Peripheral Neuropathy
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I/Group A (Duloxetine then Placebo) Patients receive oral duloxetine hydrochloride once or twice daily in weeks 1-6. After a 1-week rest period, patients cross over to receive an oral placebo once or twice daily in weeks 8-13.	Drug: duloxetine hydrochloride; Given orally; Other: placebo; Given orally
Experimental: Arm II/Group B (Placebo then Duloxetine) Patients receive an oral placebo once or twice daily in weeks 1-6. After a 1-week rest period, patients cross over to receive oral duloxetine hydrochloride once or twice daily in weeks 8-13.	Drug: duloxetine hydrochloride; Given orally; Other: placebo; Given orally

Outcome Measures

Primary Outcome Measures

1. Change in Average Pain From Week 1 to Week 5, as Measured by the BPI-SF Average Pain Severity Item [Day 1 of Week 1 to Day 1 of Week 6]

   Change in average pain from Week 1 to Week 5, measured on day 1 of Weeks 1 and 6 by the Brief Pain Inventory Short Form (BPI-SF) was calculated as value at Day 1 of Week 1 minus value at Day 1 of Week 6 to yield positive improvement values. The BPI-SF contains 4 items assessing average, worst, least, and intermediate pain severity in the last 24 hours. Pain severity items are scored using an 11-point numeric rating scale (0, no pain; 10, pain as bad as you can imagine). Average pain severity was chosen as the primary outcome based on recommendations from the Initiative on Methods, Measurements, and Pain Assessment in Clinical Trials (IMMPACT). Patients completed the BPI-SF when thinking only about pain from peripheral neuropathy. The Cronbach's alpha reliability for the BPI ranges between 0.77 and 0.91. The comparison of interest was the difference between the 2 treatment groups in pain change during the initial treatment period.

Secondary Outcome Measures

1. Change in Pain-related Functional Interference Score From Week 1 to Week 5, as Measured by the BPI-SF Interference Score [Day 1 of Week 1 to Day 1 to Week 6]

   Change in pain-related functional interference score during the initial treatment period (Week 1 to Week 5), as measured by the BPI-SF interference score: Using an accepted method for accessing the influence of pain on function, 7 BPI-SF items were used to quantify the degree to which pain interfered with daily activities or function (0, does not interfere; 10 completely interferes). The 7 items were summed to obtain a total interference score, which ranged from 0 to 70, with lower scores meaning less interference. The mean change in pain-related functional interference score during the initial treatment period are reported below for each treatment arm and was calculated as value at Day 1 of Week 1 minus value at Day 1 of Week 6 to yield positive improvement values.

2. Change in the Total Score of the FACT/COG-NTX From Week 1 to Week 5 [Day 1 of Week 1 to Day 1 of Week 6]

   Patient-reported QOL was assessed using the Functional Assessment of Cancer Treatment, Gynecologic Oncology Group Neurotoxicity (FACT/GOG-Ntx) subscale on day 1 of weeks 1, 6, 8, and 13. The instrument contains 11 questions, assessing numbness, tingling, and discomfort in the hands or feet; difficulty hearing; tinnitus; joint pain or muscle cramps; weakness; or trouble walking, buttoning buttons, or feeling small shapes when placed in the hand. Items are scored from 0 to 4 (o, not at all; 4, very much) and summed (total score range, 0-44, with higher scores indicating a worse outcome). A 2- to 3-point change is defined as a clinically meaningful improvement in QOL per published recommendations specific to similar measures. The Mean Change During Initial Treatment Period in the FACT/GOG-Ntx total score are reported for each treatment arm and was calculated as value at Day 1 of Week 1 minus value at Day 1 of Week 6 to yield positive improvement values.

3. Change in Average Pain From Week 8 to Week 12, as Measured by the BPI-SF Average Pain Severity Item [Day 1 of Week 8 to Day 1 of Week 13]

   Change in average pain from Week 8 to Week 12, measured on day 1 of Weeks 8 and 13 by the Brief Pain Inventory Short Form (BPI-SF) was calculated as value at Day 1 of Week 8 minus value at Day 1 of Week 13 to yield positive improvement values. The BPI-SF contains 4 items assessing average, worst, least, and intermediate pain severity in the last 24 hours. Pain severity items are scored using an 11-point numeric rating scale (0, no pain; 10, pain as bad as you can imagine). Average pain severity was chosen as the primary outcome based on recommendations from the Initiative on Methods, Measurements, and Pain Assessment in Clinical Trials (IMMPACT). Patients completed the BPI-SF when thinking only about pain from peripheral neuropathy. The Cronbach's alpha reliability for the BPI ranges between 0.77 and 0.91. The comparison of interest was the difference between the 2 treatment groups in pain change during the crossover treatment period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of cancer

• CNS malignancy allowed with the exception of leptomeningeal carcinomatosis

• Must have painful sensory chemotherapy-induced peripheral neuropathy (CIPN) resulting from prior treatment with single-agent taxane or platinum agents (paclitaxel, docetaxel, nab-paclitaxel, oxaliplatin, cisplatin) (may not have received drugs from both classes)

• CIPN > grade 1 as measured by NCI-CTCAE v 4.0

• Average neuropathic pain score ≥ 4

• Patients with the following illnesses known to cause peripheral neuropathy are eligible, provided they have no evidence of neuropathy from these illnesses:

• Diabetes mellitus

• Peripheral vascular disease

• HIV infection

• Significant degenerative or familial neurologic disorder known to cause peripheral neuropathy

• No clinical or subclinical neuropathy from nerve compression injuries (i.e., carpal tunnel syndrome, brachial plexopathy, spinal stenosis, or spinal nerve root compression)

PATIENT CHARACTERISTICS:

• AST ≤ 3 times upper limit of normal

• Total bilirubin ≤ normal

• Creatinine clearance > 30 mL/min

• Not pregnant or nursing

• Able to take oral or enteral medication

• No history of seizure disorder

• No diagnosis of ethanol addiction or dependence within the past 10 years

• No history of narrow-angle glaucoma

• None of the following:

• History of suicidal thoughts

• Symptoms of or history of schizophrenia, bipolar disease, or a major depression

• Serious eating disorder such as bulimia or anorexia where electrolyte imbalance is likely

PRIOR CONCURRENT THERAPY:

• At least 3 months since prior and no concurrent taxane or platinum agent

• At least 14 days since prior and no concurrent monoamine oxidase inhibitors or other antidepressants

• No other prior or concurrent neurotoxic drugs (e.g., vincristine, vinblastine, cytarabine, thalidomide, bortezomib, carboplatin, or procarbazine)

• No concurrent anticonvulsants

• No concurrent B or E vitamin supplementation in doses greater than the recommended daily allowance (RDA)

• Centrum (standard formula) and One-A-Day "essential" formula which contain 100% RDA for vitamins B6, E, and B12 allowed

• Other multivitamins allowed provided they contain no more than 100% RDA of B vitamins and vitamin E

• No concurrent treatment (pharmacologic) for depression

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaiser Permanente - Deer Valley	Antioch	California	United States	94531
2	Alta Bates Summit Comprehensive Cancer Center	Berkeley	California	United States	94704
3	Peninsula Medical Center	Burlingame	California	United States	94010
4	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
5	Valley Medical Oncology Consultants - Castro Valley	Castro Valley	California	United States	94546
6	Cancer Care Center at John Muir Health - Concord Campus	Concord	California	United States	94524-4110
7	Kaiser Permanente - Fremont	Fremont	California	United States	94538
8	Valley Medical Oncology	Fremont	California	United States	94538
9	Glendale Memorial Hospital Comprehensive Cancer Center	Glendale	California	United States	91204
10	Kaiser Permanente Medical Center - Hayward	Hayward	California	United States	94545
11	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
12	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California	United States	90089-9181
13	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
14	Camino Medical Group - Treatment Center	Mountain View	California	United States	94040
15	El Camino Hospital Cancer Center	Mountain View	California	United States	94040
16	Highland General Hospital	Oakland	California	United States	94602
17	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
18	Bay Area Breast Surgeons, Incorporated	Oakland	California	United States	94609
19	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609
20	Larry G Strieff MD Medical Corporation	Oakland	California	United States	94609
21	Tom K Lee, Incorporated	Oakland	California	United States	94609
22	Kaiser Permanente - Division of Research - Oakland	Oakland	California	United States	94611
23	Kaiser Permanente Medical Center - Oakland	Oakland	California	United States	94611
24	Palo Alto Medical Foundation	Palo Alto	California	United States	94301
25		Pismo Beach	California	United States	93449
26	Kaiser Permanente Medical Center - Rancho Cordova	Rancho Cardova	California	United States	95670
27	Kaiser Permanente Medical Center - Redwood City	Redwood City	California	United States	94063
28	Kaiser Permanente Medical Center - Richmond	Richmond	California	United States	94801
29	Rohnert Park Cancer Center	Rohnert Park	California	United States	94928
30	Kaiser Permanente Medical Center - Roseville	Roseville	California	United States	95661
31	Sutter Cancer Center at Roseville Medical Center	Roseville	California	United States	95661
32	Sutter Cancer Center	Sacramento	California	United States	95816
33	South Sacramento Cancer Center	Sacramento	California	United States	95823
34	South Sacramento Kaiser-Permanente Medical Center	Sacramento	California	United States	95823
35	Kaiser Permanente Medical Center - Sacramento	Sacramento	California	United States	95825
36	Kaiser Permanente Medical Office -Vandever Medical Office	San Diego	California	United States	92120
37	Kaiser Permanente Medical Center - San Francisco Geary Campus	San Francisco	California	United States	94115
38	California Pacific Medical Center - California Campus	San Francisco	California	United States	94118
39	Kaiser Permanente Medical Center - Santa Teresa	San Jose	California	United States	95119
40	Doctors Medical Center - San Pablo Campus	San Pablo	California	United States	94806
41	Kaiser Foundation Hospital - San Rafael	San Rafael	California	United States	94903
42	Sutter Health - Western Division Cancer Research Group	San Rafael	California	United States	94903
43	Kaiser Permanente Medical Center - Santa Clara Kiely Campus	Santa Clara	California	United States	95051
44		Santa Clara	California	United States	95051
45	Kaiser Permanente Medical Center - Santa Rosa	Santa Rosa	California	United States	95403
46	Kaiser Permanente Medical Center - South San Francisco	South San Francisco	California	United States	94080
47	Kaiser Permanente Medical Facility - Stockton	Stockton	California	United States	95210
48	Kaiser Permanente Medical Center - Vacaville	Vacaville	California	United States	95688
49	Kaiser Permanente Medical Center - Vallejo	Vallejo	California	United States	94589
50	Sutter Solano Medical Center	Vallejo	California	United States	94589
51	Kaiser Permanente Medical Center - Walnut Creek	Walnut Creek	California	United States	94596
52	John Muir/Mt. Diablo Comprehensive Cancer Center	Walnut Creek	California	United States	94598
53	Aurora Presbyterian Hospital	Aurora	Colorado	United States	80012
54	Boulder Community Hospital	Boulder	Colorado	United States	80301-9019
55	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado	United States	80933
56	St. Anthony Central Hospital	Denver	Colorado	United States	80204
57	Kaiser Permanente - Denver	Denver	Colorado	United States	80205
58	Porter Adventist Hospital	Denver	Colorado	United States	80210
59	Presbyterian - St. Luke's Medical Center	Denver	Colorado	United States	80218
60	St. Joseph Hospital	Denver	Colorado	United States	80218
61	Rose Medical Center	Denver	Colorado	United States	80220
62	CCOP - Colorado Cancer Research Program	Denver	Colorado	United States	80224-2522
63	Swedish Medical Center	Englewood	Colorado	United States	80110
64	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
65	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
66	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado	United States	81502
67	North Colorado Medical Center	Greeley	Colorado	United States	80631
68	Kaiser Permanente - Lafayette	Lafayette	Colorado	United States	80026
69	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
70	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado	United States	80501
71	McKee Medical Center	Loveland	Colorado	United States	80539
72	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado	United States	81004
73	North Suburban Medical Center	Thornton	Colorado	United States	80229
74	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
75	Bendheim Cancer Center at Greenwich Hospital	Greenwich	Connecticut	United States	06830
76	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
77	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware	United States	19958
78	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
79	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
80	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5001
81	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
82	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida	United States	33021
83	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida	United States	33458
84	Lakeland Regional Cancer Center at Lakeland Regional Medical Center	Lakeland	Florida	United States	33805
85	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
86	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida	United States	32803-1273
87	Cleveland Clinic Florida - Weston	Weston	Florida	United States	33331
88	Piedmont Hospital	Atlanta	Georgia	United States	30309
89	Northside Hospital Cancer Center	Atlanta	Georgia	United States	30342-1611
90	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia	United States	30342-1701
91	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342
92	WellStar Cobb Hospital	Austell	Georgia	United States	30106
93	John B. Amos Cancer Center	Columbus	Georgia	United States	31904
94	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia	United States	30033
95	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
96	Gwinnett Medical Center	Lawrenceville	Georgia	United States	30045
97	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia	United States	30060
98	Southern Regional Medical Center	Riverdale	Georgia	United States	30274-2600
99	Harbin Clinic Cancer Center - Medical Oncology	Rome	Georgia	United States	30165
100	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia	United States	31405
101	Kaiser Permanente - Moanalua Medical Center and Clinic	Honolulu	Hawaii	United States	96819
102	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois	United States	62002
103	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60504
104	Illinois CancerCare - Bloomington	Bloomington	Illinois	United States	61701
105	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
106	Graham Hospital	Canton	Illinois	United States	61520
107	Illinois CancerCare - Canton	Canton	Illinois	United States	61520
108	Illinois CancerCare - Carthage	Carthage	Illinois	United States	62321
109	Memorial Hospital	Carthage	Illinois	United States	62321
110	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois	United States	60612-3785
111	Resurrection Medical Center	Chicago	Illinois	United States	60631
112	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
113	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
114	Elmhurst Memorial Hospital	Elmhurst	Illinois	United States	60126
115	Eureka Community Hospital	Eureka	Illinois	United States	61530
116	Illinois CancerCare - Eureka	Eureka	Illinois	United States	61530
117	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
118	Illinois CancerCare - Galesburg	Galesburg	Illinois	United States	61401
119	Illinois CancerCare - Havana	Havana	Illinois	United States	62644
120	Mason District Hospital	Havana	Illinois	United States	62644
121	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
122	Illinois CancerCare - Kewanee Clinic	Kewanee	Illinois	United States	61443
123	La Grange Memorial Hospital	La Grange	Illinois	United States	60525
124	Illinois CancerCare - Macomb	Macomb	Illinois	United States	61455
125	McDonough District Hospital	Macomb	Illinois	United States	61455
126	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois	United States	60153
127	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois	United States	61265
128		Moline	Illinois	United States	61265
129	Illinois CancerCare - Monmouth	Monmouth	Illinois	United States	61462
130	OSF Holy Family Medical Center	Monmouth	Illinois	United States	61462
131	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
132	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
133	Community Cancer Center	Normal	Illinois	United States	61761
134	Illinois CancerCare - Community Cancer Center	Normal	Illinois	United States	61761
135	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
136	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
137	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
138	Illinois CancerCare - Pekin	Pekin	Illinois	United States	61603
139	Proctor Hospital	Peoria	Illinois	United States	61614
140	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
141	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
142	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
143	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
144	Illinois CancerCare - Peru	Peru	Illinois	United States	61354
145	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
146	Illinois CancerCare - Princeton	Princeton	Illinois	United States	61356
147	Perry Memorial Hospital	Princeton	Illinois	United States	61356
148	Swedish-American Regional Cancer Center	Rockford	Illinois	United States	61104-2315
149	Illinois CancerCare - Spring Valley	Spring Valley	Illinois	United States	61362
150	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
151	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
152	Central Dupage Cancer Center	Warrenville	Illinois	United States	60555
153	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
154	Elkhart Clinic, LLC	Elkhart	Indiana	United States	46514-2098
155	Michiana Hematology-Oncology, PC - Elkhart	Elkhart	Indiana	United States	46514
156	Elkhart General Hospital	Elkhart	Indiana	United States	46515
157	Howard Community Hospital	Kokomo	Indiana	United States	46904
158	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
159	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
160	Michiana Hematology-Oncology, PC - South Bend	Mishawaka	Indiana	United States	46545-1470
161	Saint Joseph Regional Medical Center	Mishawaka	Indiana	United States	46545-1470
162	Michiana Hematology Oncology PC - Plymouth	Plymouth	Indiana	United States	46563
163	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
164	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
165	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
166	South Bend Clinic	South Bend	Indiana	United States	46617
167	Michiana Hematology Oncology PC - La Porte	Westville	Indiana	United States	46391
168	McFarland Clinic, PC	Ames	Iowa	United States	50010
169		Bettendorf	Iowa	United States	52722
170	Iowa Blood and Cancer Care	Cedar Rapids	Iowa	United States	52402
171	St. Luke's Hospital	Cedar Rapids	Iowa	United States	52402
172	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa	United States	52403
173	Mercy Regional Cancer Center at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
174	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa	United States	50325
175	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
176	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
177	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
178	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
179	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
180	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
181	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
182	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
183	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
184	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
185	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
186	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
187	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
188	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
189	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
190	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
191	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
192	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas	United States	67905
193	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
194	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
195	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
196	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
197	Cotton-O'Neil Cancer Center	Topeka	Kansas	United States	66606
198	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
199	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
200	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
201	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
202	CCOP - Wichita	Wichita	Kansas	United States	67214
203	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
204	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
205	Cancer Resource Center at King's Daughters Medical Center	Ashland	Kentucky	United States	41101-0151
206	Central Baptist Hospital	Lexington	Kentucky	United States	40503-9985
207	Harold Alfond Center for Cancer Care	Augusta	Maine	United States	04330
208	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
209	Shore Regional Cancer Center at Memorial Hospital - Easton	Easton	Maryland	United States	21601
210	Union Hospital Cancer Program at Union Hospital	Elkton MD	Maryland	United States	21921
211	Sturdy Memorial Hospital	Attleboro	Massachusetts	United States	02703
212	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
213	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
214	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
215	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
216	Green Bay Oncology, Limited - Escanaba	Escanaba	Michigan	United States	49431
217	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
218	Hurley Medical Center	Flint	Michigan	United States	48503
219	Great Lakes Cancer Institute at McLaren Regional Medical Center	Flint	Michigan	United States	48532
220	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
221	Dickinson County Healthcare System	Iron Mountain	Michigan	United States	49801
222	Foote Memorial Hospital	Jackson	Michigan	United States	49201
223	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
224	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
225	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
226	Haematology-Oncology Associates of Ohio and Michigan, PC	Lambertville	Michigan	United States	48144
227	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan	United States	48910
228	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
229	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
230	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
231	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
232	Michiana Hematology Oncology PC - Niles	Niles	Michigan	United States	49120
233	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
234	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
235	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan	United States	48073
236	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
237	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan	United States	49085
238	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan	United States	49085
239	St. John Macomb Hospital	Warren	Michigan	United States	48093
240	MeritCare Bemidji	Bemidji	Minnesota	United States	56601
241	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
242	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
243	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
244	CCOP - Duluth	Duluth	Minnesota	United States	55805
245	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
246	St. Luke's Hospital Cancer Care Center	Duluth	Minnesota	United States	55805
247	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
248	Fergus Falls Medical Group, PA	Fergus Falls	Minnesota	United States	56537
249	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
250	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
251	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
252	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
253	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
254	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
255	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
256	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
257	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
258	United Hospital	Saint Paul	Minnesota	United States	55102
259	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
260	Regions Hospital Cancer Care Center	St. Paul	Minnesota	United States	55101
261	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
262	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota	United States	56201
263	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
264	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
265	Saint Luke's Hospital	Chesterfield	Missouri	United States	63017
266	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
267	Midwest Hematology Oncology Group, Incorporated	Saint Louis	Missouri	United States	63109
268	St. Anthony's Cancer Center	Saint Louis	Missouri	United States	63128
269	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
270	Arch Medical Services, Incorporated at Center for Cancer Care and Research	Saint Louis	Missouri	United States	63141
271	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
272	Comprehensive Cancer Care, PC	Saint Louis	Missouri	United States	63141
273	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri	United States	63141
274	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
275	St. John's Regional Health Center	Springfield	Missouri	United States	65804
276	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
277	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
278	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
279	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
280	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59102
281	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
282	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
283	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
284	Big Sky Oncology	Great Falls	Montana	United States	59405-5309
285	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
286	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
287	Northern Montana Hospital	Havre	Montana	United States	59501
288	St. Peter's Hospital	Helena	Montana	United States	59601
289	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
290	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
291	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
292	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
293	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
294	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
295	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
296	Immanuel Medical Center	Omaha	Nebraska	United States	68122
297	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
298	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
299	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
300	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
301	New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care	Concord	New Hampshire	United States	03301
302	Center for Cancer Care at Exeter Hospital	Exeter	New Hampshire	United States	03833
303	New Hampshire Oncology - Hematology, PA - Hooksett	Hooksett	New Hampshire	United States	03106
304	Lakes Region General Hospital	Laconia	New Hampshire	United States	03246
305	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
306	Norris Cotton Cancer Center at Catholic Medical Center	Manchester	New Hampshire	United States	03102
307	Hunterdon Regional Cancer Center at Hunterdon Medical Center	Flemington	New Jersey	United States	08822
308	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08901
309	Somerset Medical Center	Somerville	New Jersey	United States	08876
310	Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare	Vineland	New Jersey	United States	08360
311	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
312	New York Oncology Hematology, PC at Albany Regional Cancer Care	Albany	New York	United States	12206
313	New York Oncology Hematology, PC at Albany Medical Center	Albany	New York	United States	12208
314	Amsterdam Community Cancer Program	Amsterdam	New York	United States	12010
315	Veterans Affairs Medical Center - Brooklyn	Brooklyn	New York	United States	11209
316	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York	United States	13057
317	Charles R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York	United States	12801
318	New York Oncology Hematology, PC - Hudson	Hudson	New York	United States	12534
319	Queens Cancer Center of Queens Hospital	Jamaica	New York	United States	11432
320	New York Oncology Hematology, PC - Latham	Latham	New York	United States	12110
321	New York Weill Cornell Cancer Center at Cornell University	New York	New York	United States	10021
322	Mount Sinai Medical Center	New York	New York	United States	10029
323	Riverview Cancer Care Medical Associates, PC	Rexford	New York	United States	12148
324	Nalitt Cancer Institute at Staten Island University Hospital	Staten Island	New York	United States	10305
325	Veterans Affairs Medical Center - Syracuse	Syracuse	New York	United States	13210
326	Samaritan Hospital at Northeast Health	Troy	New York	United States	12180
327	Dickstein Cancer Treatment Center at White Plains Hospital Center	White Plains	New York	United States	10601
328	Waverly Hematology Oncology	Cary	North Carolina	United States	27511
329	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
330	Batte Cancer Center at Northeast Medical Center	Concord	North Carolina	United States	28025
331	CaroMont Cancer Center at Gaston Memorial Hospital	Gastonia	North Carolina	United States	28053
332	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
333	Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
334	High Point Regional Hospital	High Point	North Carolina	United States	27261
335	Emerywood Hematology/Oncology	High Point	North Carolina	United States	27262
336	Kinston Medical Specialists	Kinston	North Carolina	United States	28501
337	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
338	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
339	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
340	Medcenter One Hospital Cancer Care Center	Bismarck	North Dakota	United States	58501
341	Mid Dakota Clinic, PC	Bismarck	North Dakota	United States	58501
342	St. Alexius Medical Center Cancer Center	Bismarck	North Dakota	United States	58502
343	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
344	MeritCare Broadway	Fargo	North Dakota	United States	58122
345	Trinity CancerCare Center	Minot	North Dakota	United States	58701
346	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio	United States	44307
347	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio	United States	44309-2090
348	Barberton Citizens Hospital	Barberton	Ohio	United States	44203
349	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
350	Wood County Oncology Center	Bowling Green	Ohio	United States	43402
351	Aultman Cancer Center at Aultman Hospital	Canton	Ohio	United States	44710-1799
352	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
353	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio	United States	44109
354	North Coast Cancer Care - Clyde	Clyde	Ohio	United States	43410
355	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
356	CCOP - Columbus	Columbus	Ohio	United States	43215
357	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
358	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
359	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
360	Grandview Hospital	Dayton	Ohio	United States	45405
361	Good Samaritan Hospital	Dayton	Ohio	United States	45406
362	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
363	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
364	CCOP - Dayton	Dayton	Ohio	United States	45420
365	Grady Memorial Hospital	Delaware	Ohio	United States	43015
366	Community Cancer Center	Elyria	Ohio	United States	44035
367	Hematology Oncology Center	Elyria	Ohio	United States	44035
368	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
369	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
370	Wayne Hospital	Greenville	Ohio	United States	45331
371	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
372	Fairfield Medical Center	Lancaster	Ohio	United States	43130
373	St. Rita's Medical Center	Lima	Ohio	United States	45801
374	Lima Memorial Hospital	Lima	Ohio	United States	45804
375	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
376	Northwest Ohio Oncology Center	Maumee	Ohio	United States	43537-1839
377	St. Luke's Hospital	Maumee	Ohio	United States	43537
378	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
379	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
380	Fisher-Titus Medical Center	Norwalk	Ohio	United States	44857
381	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
382	Toledo Clinic - Oregon	Oregon	Ohio	United States	43616
383	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
384	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
385	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
386	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
387	Toledo Hospital	Toledo	Ohio	United States	43606
388	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
389	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
390	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
391	St. Anne Mercy Hospital	Toledo	Ohio	United States	43623
392	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
393	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
394	Fulton County Health Center	Wauseon	Ohio	United States	43567
395	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
396	United States Air Force Medical Center - Wright-Patterson	Wright-Patterson Afb	Ohio	United States	45433-5529
397	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
398	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
399	Bay Area Hospital	Coos Bay	Oregon	United States	97420
400	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania	United States	18105
401	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
402	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
403	Doylestown Hospital Cancer Center	Doylestown	Pennsylvania	United States	18901
404	Delaware County Regional Cancer Center at Delaware County Memorial Hospital	Drexel Hill	Pennsylvania	United States	19026
405	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania	United States	18201
406	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301-1792
407	Cancer Center at Phoenixville Hospital	Phoenixville	Pennsylvania	United States	19460
408	Pottstown Memorial Regional Cancer Center	Pottstown	Pennsylvania	United States	19464
409	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
410	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
411	CCOP - Main Line Health	Wynnewood	Pennsylvania	United States	19096
412	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania	United States	19096
413	Roper St. Francis Cancer Center at Roper Hospital	Charleston	South Carolina	United States	29401
414	McLeod Regional Medical Center	Florence	South Carolina	United States	29501
415	Bon Secours St. Francis Health System	Greenville	South Carolina	United States	29601
416	Cancer Centers of the Carolinas - Faris Road	Greenville	South Carolina	United States	29605
417	Cancer Centers of the Carolinas - Grove Commons	Greenville	South Carolina	United States	29605
418	Greenville Hospital Cancer Center	Greenville	South Carolina	United States	29605
419	CCOP - Greenville	Greenville	South Carolina	United States	29615
420	Self Regional Cancer Center at Self Regional Medical Center	Greenwood	South Carolina	United States	29646
421	Cancer Centers of the Carolinas - Greer Medical Oncology	Greer	South Carolina	United States	29650
422	Cancer Centers of the Carolinas - Seneca	Seneca	South Carolina	United States	29672
423	Cancer Centers of the Carolinas - Spartanburg	Spartanburg	South Carolina	United States	29307
424	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
425	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234-6200
426	Martha Jefferson Hospital Cancer Care Center	Charlottesville	Virginia	United States	22901
427	Danville Regional Medical Center	Danville	Virginia	United States	24541
428	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
429	Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County	Martinsville	Virginia	United States	24115
430	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia	United States	23298-0037
431	Schiffler Cancer Center at Wheeling Hospital	Wheeling	West Virginia	United States	26003
432	Aurora Memorial Hospital of Burlington	Burlington	Wisconsin	United States	53105
433	Marshfield Clinic - Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
434	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin	United States	54701
435	Vince Lombardi Cancer Center at Aurora Lakeland Medical Center - Elkhorn	Elkhorn	Wisconsin	United States	53121
436	Oncology Alliance - Franklin	Franklin	Wisconsin	United States	53132
437	Oncology Alliance, SC - Milwaukee - East	Glendale	Wisconsin	United States	53212-1038
438	Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54301-3526
439	Green Bay Oncology, Limited at St. Mary's Hospital	Green Bay	Wisconsin	United States	54303
440	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin	United States	54303
441	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
442	Vince Lombardi Cancer Clinic - Green Bay at Aurora BayCare Medical Center	Green Bay	Wisconsin	United States	54311
443	Mercy Regional Cancer Center	Janesville	Wisconsin	United States	53547
444	Oncology Alliance - Kenosha South	Kenosha	Wisconsin	United States	53143
445	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin	United States	54601
446	Dean Medical Center - Madison	Madison	Wisconsin	United States	53717
447	Holy Family Memorial Medical Center Cancer Care Center	Manitowoc	Wisconsin	United States	54221-1450
448	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin	United States	54143
449	Vince Lombardi Cancer Clinic - Marinette	Marinette	Wisconsin	United States	54143
450	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
451	Aurora Advanced Healthcare East Mequon Clinic	Mequon	Wisconsin	United States	53092
452	Aurora Sinai Medical Center	Milwaukee	Wisconsin	United States	53201-0342
453	Medical Consultants, Limited	Milwaukee	Wisconsin	United States	53215
454	Oncology Alliance, SC - Milwaukee - South	Milwaukee	Wisconsin	United States	53215
455	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin	United States	54548
456	Regional Cancer Center at Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin	United States	53066
457	Green Bay Oncology, Limited - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
458	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
459	Aurora Health Center - Racine	Racine	Wisconsin	United States	53406-5661
460	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
461	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin	United States	54868
462	Vince Lombardi Cancer Clinic - Sheboygan	Sheboygan	Wisconsin	United States	53081
463	Marshfield Clinic at Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
464	Green Bay Oncology, Limited - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
465	Aurora Medical Center	Summit	Wisconsin	United States	53066
466	Vince Lombardi Cancer Clinic - Two Rivers	Two Rivers	Wisconsin	United States	54241
467	Aurora Health Center - Waukesha	Waukesha	Wisconsin	United States	53188
468	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin	United States	53188
469	Marshfield Clinic - Wausau Center	Wausau	Wisconsin	United States	54401
470	Oncology Alliance, SC - Milwaukee - West	Wauwatosa	Wisconsin	United States	53226
471	Aurora Women's Pavilion of West Allis Memorial Hospital	West Allis	Wisconsin	United States	53227
472	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
473	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
474	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
475	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

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

Investigators

• Study Chair: Ellen L. Smith, PhD, ARNP, AOCN, University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00489411
• Other Study ID Numbers: CALGB-170601; CALGB-170601; CDR0000553389
• First Posted: Jun 21, 2007
• Last Update Posted: Apr 26, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Alliance for Clinical Trials in Oncology: unspecified adult solid tumor, protocol specific; neurotoxicity; pain; peripheral neuropathy
• Additional relevant MeSH terms: Peripheral Nervous System Diseases; Neurotoxicity Syndromes; Duloxetine Hydrochloride

Study Results

Participant Flow

Pre-assignment Detail	The number of screened and the number offered participation but declined was not captured.

Arm/Group Title	Arm I/Group A (Duloxetine Then Placebo)	Arm II/Group B (Placebo Then Duloxetine)
Arm/Group Description	Patients will take one capsule of 30 mg duloxetine orally daily for 7 days (week 1), and then increase to two capsules of duloxetine (60 mg duloxetine) orally daily for 28 days (weeks 2-5). Duloxetine will be tapered during week 6 (one capsule daily for 7 days), and will be discontinued during week 7 (no capsules for 7 days). Patients will then cross over to receive the alternative treatment (placebo), and the sequence will be repeated. Patients will take one capsule of placebo daily for 7 days (week 8), two capsules of placebo daily for 28 days (weeks 9-12), one capsule of placebo daily for 7 days (week 13), and then no capsules for 7 days (week 14).	Patients will take one capsule of placebo orally daily for 7 days (week 1), and then increase to two capsules of placebo orally daily for 28 days (weeks 2-5). Placebo will be tapered during week 6 (one capsule daily for 7 days), and will be discontinued during week 7 (no capsules for 7 days). Patients will then cross over to receive the alternative treatment (duloxetine), and the sequence will be repeated. Patients will take one capsule of duloxetine daily for 7 days (week 8), two capsules of duloxetine daily for 28 days (weeks 9-12), one capsule of duloxetine daily for 7 days (week 13), and then no capsules for 7 days (week 14).
Period Title: Initial Treatment Period (Weeks 1-5)
STARTED	115	116
COMPLETED	87	94
NOT COMPLETED	28	22
Period Title: Initial Treatment Period (Weeks 1-5)
STARTED	87	94
COMPLETED	85	93
NOT COMPLETED	2	1
Period Title: Initial Treatment Period (Weeks 1-5)
STARTED	85	93
COMPLETED	67	74
NOT COMPLETED	18	19

Baseline Characteristics

Arm/Group Title	Arm I/Group A (Duloxetine Then Placebo)	Arm II/Group B (Placebo Then Duloxetine)	Total
Arm/Group Description	Patients will take one capsule of 30 mg duloxetine orally daily for 7 days (week 1), and then increase to two capsules of duloxetine (60 mg duloxetine) orally daily for 28 days (weeks 2-5). Duloxetine will be tapered during week 6 (one capsule daily for 7 days), and will be discontinued during week 7 (no capsules for 7 days). Patients will then cross over to receive the alternative treatment (placebo), and the sequence will be repeated. Patients will take one capsule of placebo daily for 7 days (week 8), two capsules of placebo daily for 28 days (weeks 9-12), one capsule of placebo daily for 7 days (week 13), and then no capsules for 7 days (week 14).	Patients will take one capsule of placebo orally daily for 7 days (week 1), and then increase to two capsules of placebo orally daily for 28 days (weeks 2-5). Placebo will be tapered during week 6 (one capsule daily for 7 days), and will be discontinued during week 7 (no capsules for 7 days). Patients will then cross over to receive the alternative treatment (duloxetine), and the sequence will be repeated. Patients will take one capsule of duloxetine daily for 7 days (week 8), two capsules of duloxetine daily for 28 days (weeks 9-12), one capsule of duloxetine daily for 7 days (week 13), and then no capsules for 7 days (week 14).	Total of all reporting groups
Overall Participants	109	111	220
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.0 (10.4)	59.0 (10.6)	59.0 (10.5)
Sex: Female, Male (Count of Participants)
Female	71 65.1%	67 60.4%	138 62.7%
Male	38 34.9%	44 39.6%	82 37.3%
Region of Enrollment (participants) [Number]
United States	109 100%	111 100%	220 100%

Outcome Measures

1. Primary Outcome

Title	Change in Average Pain From Week 1 to Week 5, as Measured by the BPI-SF Average Pain Severity Item
Description	Change in average pain from Week 1 to Week 5, measured on day 1 of Weeks 1 and 6 by the Brief Pain Inventory Short Form (BPI-SF) was calculated as value at Day 1 of Week 1 minus value at Day 1 of Week 6 to yield positive improvement values. The BPI-SF contains 4 items assessing average, worst, least, and intermediate pain severity in the last 24 hours. Pain severity items are scored using an 11-point numeric rating scale (0, no pain; 10, pain as bad as you can imagine). Average pain severity was chosen as the primary outcome based on recommendations from the Initiative on Methods, Measurements, and Pain Assessment in Clinical Trials (IMMPACT). Patients completed the BPI-SF when thinking only about pain from peripheral neuropathy. The Cronbach's alpha reliability for the BPI ranges between 0.77 and 0.91. The comparison of interest was the difference between the 2 treatment groups in pain change during the initial treatment period.
Time Frame	Day 1 of Week 1 to Day 1 of Week 6

Outcome Measure Data

Analysis Population Description

Patients who completed initial intervention (prior to crossing over to receive alternate study drug duloxetine or placebo) and had complete data were included in the primary analysis.

Arm/Group Title	Arm I/Group A (Duloxetine Then Placebo)	Arm II/Group B (Placebo Then Duloxetine)
Arm/Group Description	Patients will take one capsule of 30 mg duloxetine orally daily for 7 days (week 1), and then increase to two capsules of duloxetine (60 mg duloxetine) orally daily for 28 days (weeks 2-5). Duloxetine will be tapered during week 6 (one capsule daily for 7 days), and will be discontinued during week 7 (no capsules for 7 days). Patients will then cross over to receive the alternative treatment (placebo), and the sequence will be repeated. Patients will take one capsule of placebo daily for 7 days (week 8), two capsules of placebo daily for 28 days (weeks 9-12), one capsule of placebo daily for 7 days (week 13), and then no capsules for 7 days (week 14).	Patients will take one capsule of placebo orally daily for 7 days (week 1), and then increase to two capsules of placebo orally daily for 28 days (weeks 2-5). Placebo will be tapered during week 6 (one capsule daily for 7 days), and will be discontinued during week 7 (no capsules for 7 days). Patients will then cross over to receive the alternative treatment (duloxetine), and the sequence will be repeated. Patients will take one capsule of duloxetine daily for 7 days (week 8), two capsules of duloxetine daily for 28 days (weeks 9-12), one capsule of duloxetine daily for 7 days (week 13), and then no capsules for 7 days (week 14).
Measure Participants	87	94
Mean (95% Confidence Interval) [units on a scale]	1.06	0.34

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I/Group A (Duloxetine Then Placebo), Arm II/Group B (Placebo Then Duloxetine)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.26 to 1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in Pain-related Functional Interference Score From Week 1 to Week 5, as Measured by the BPI-SF Interference Score
Description	Change in pain-related functional interference score during the initial treatment period (Week 1 to Week 5), as measured by the BPI-SF interference score: Using an accepted method for accessing the influence of pain on function, 7 BPI-SF items were used to quantify the degree to which pain interfered with daily activities or function (0, does not interfere; 10 completely interferes). The 7 items were summed to obtain a total interference score, which ranged from 0 to 70, with lower scores meaning less interference. The mean change in pain-related functional interference score during the initial treatment period are reported below for each treatment arm and was calculated as value at Day 1 of Week 1 minus value at Day 1 of Week 6 to yield positive improvement values.
Time Frame	Day 1 of Week 1 to Day 1 to Week 6

Outcome Measure Data

Analysis Population Description

Patients who completed initial intervention (prior to crossing over to receive alternate study drug duloxetine or placebo) and had complete data were included in the primary analysis.

Arm/Group Title	Arm I/Group A (Duloxetine Then Placebo)	Arm II/Group B (Placebo Then Duloxetine)
Arm/Group Description	Patients will take one capsule of 30 mg duloxetine orally daily for 7 days (week 1), and then increase to two capsules of duloxetine (60 mg duloxetine) orally daily for 28 days (weeks 2-5). Duloxetine will be tapered during week 6 (one capsule daily for 7 days), and will be discontinued during week 7 (no capsules for 7 days). Patients will then cross over to receive the alternative treatment (placebo), and the sequence will be repeated. Patients will take one capsule of placebo daily for 7 days (week 8), two capsules of placebo daily for 28 days (weeks 9-12), one capsule of placebo daily for 7 days (week 13), and then no capsules for 7 days (week 14).	Patients will take one capsule of placebo orally daily for 7 days (week 1), and then increase to two capsules of placebo orally daily for 28 days (weeks 2-5). Placebo will be tapered during week 6 (one capsule daily for 7 days), and will be discontinued during week 7 (no capsules for 7 days). Patients will then cross over to receive the alternative treatment (duloxetine), and the sequence will be repeated. Patients will take one capsule of duloxetine daily for 7 days (week 8), two capsules of duloxetine daily for 28 days (weeks 9-12), one capsule of duloxetine daily for 7 days (week 13), and then no capsules for 7 days (week 14).
Measure Participants	87	94
Mean (95% Confidence Interval) [units on a scale]	7.9	3.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I/Group A (Duloxetine Then Placebo), Arm II/Group B (Placebo Then Duloxetine)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	4.40
	Confidence Interval	(2-Sided) 95%; 0.93 to 7.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change in the Total Score of the FACT/COG-NTX From Week 1 to Week 5
Description	Patient-reported QOL was assessed using the Functional Assessment of Cancer Treatment, Gynecologic Oncology Group Neurotoxicity (FACT/GOG-Ntx) subscale on day 1 of weeks 1, 6, 8, and 13. The instrument contains 11 questions, assessing numbness, tingling, and discomfort in the hands or feet; difficulty hearing; tinnitus; joint pain or muscle cramps; weakness; or trouble walking, buttoning buttons, or feeling small shapes when placed in the hand. Items are scored from 0 to 4 (o, not at all; 4, very much) and summed (total score range, 0-44, with higher scores indicating a worse outcome). A 2- to 3-point change is defined as a clinically meaningful improvement in QOL per published recommendations specific to similar measures. The Mean Change During Initial Treatment Period in the FACT/GOG-Ntx total score are reported for each treatment arm and was calculated as value at Day 1 of Week 1 minus value at Day 1 of Week 6 to yield positive improvement values.
Time Frame	Day 1 of Week 1 to Day 1 of Week 6

Outcome Measure Data

Analysis Population Description

Patients who completed initial intervention (prior to crossing over to receive alternate study drug duloxetine or placebo) and had complete data were included in the primary analysis.

Arm/Group Title	Arm I/Group A (Duloxetine Then Placebo)	Arm II/Group B (Placebo Then Duloxetine)
Arm/Group Description	Patients will take one capsule of 30 mg duloxetine orally daily for 7 days (week 1), and then increase to two capsules of duloxetine (60 mg duloxetine) orally daily for 28 days (weeks 2-5). Duloxetine will be tapered during week 6 (one capsule daily for 7 days), and will be discontinued during week 7 (no capsules for 7 days). Patients will then cross over to receive the alternative treatment (placebo), and the sequence will be repeated. Patients will take one capsule of placebo daily for 7 days (week 8), two capsules of placebo daily for 28 days (weeks 9-12), one capsule of placebo daily for 7 days (week 13), and then no capsules for 7 days (week 14).	Patients will take one capsule of placebo orally daily for 7 days (week 1), and then increase to two capsules of placebo orally daily for 28 days (weeks 2-5). Placebo will be tapered during week 6 (one capsule daily for 7 days), and will be discontinued during week 7 (no capsules for 7 days). Patients will then cross over to receive the alternative treatment (duloxetine), and the sequence will be repeated. Patients will take one capsule of duloxetine daily for 7 days (week 8), two capsules of duloxetine daily for 28 days (weeks 9-12), one capsule of duloxetine daily for 7 days (week 13), and then no capsules for 7 days (week 14).
Measure Participants	87	94
Mean (95% Confidence Interval) [units on a scale]	2.44	0.87

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I/Group A (Duloxetine Then Placebo), Arm II/Group B (Placebo Then Duloxetine)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference
	Estimated Value	1.58
	Confidence Interval	(2-Sided) 95%; 0.15 to 3.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change in Average Pain From Week 8 to Week 12, as Measured by the BPI-SF Average Pain Severity Item
Description	Change in average pain from Week 8 to Week 12, measured on day 1 of Weeks 8 and 13 by the Brief Pain Inventory Short Form (BPI-SF) was calculated as value at Day 1 of Week 8 minus value at Day 1 of Week 13 to yield positive improvement values. The BPI-SF contains 4 items assessing average, worst, least, and intermediate pain severity in the last 24 hours. Pain severity items are scored using an 11-point numeric rating scale (0, no pain; 10, pain as bad as you can imagine). Average pain severity was chosen as the primary outcome based on recommendations from the Initiative on Methods, Measurements, and Pain Assessment in Clinical Trials (IMMPACT). Patients completed the BPI-SF when thinking only about pain from peripheral neuropathy. The Cronbach's alpha reliability for the BPI ranges between 0.77 and 0.91. The comparison of interest was the difference between the 2 treatment groups in pain change during the crossover treatment period.
Time Frame	Day 1 of Week 8 to Day 1 of Week 13

Outcome Measure Data

Analysis Population Description

Patients who completed crossover intervention and had complete data were included in the analysis.

Arm/Group Title	Arm I/Group A (Duloxetine Then Placebo)	Arm II/Group B (Placebo Then Duloxetine)
Arm/Group Description	Patients will take one capsule of 30 mg duloxetine orally daily for 7 days (week 1), and then increase to two capsules of duloxetine (60 mg duloxetine) orally daily for 28 days (weeks 2-5). Duloxetine will be tapered during week 6 (one capsule daily for 7 days), and will be discontinued during week 7 (no capsules for 7 days). Patients will then cross over to receive the alternative treatment (placebo), and the sequence will be repeated. Patients will take one capsule of placebo daily for 7 days (week 8), two capsules of placebo daily for 28 days (weeks 9-12), one capsule of placebo daily for 7 days (week 13), and then no capsules for 7 days (week 14).	Patients will take one capsule of placebo orally daily for 7 days (week 1), and then increase to two capsules of placebo orally daily for 28 days (weeks 2-5). Placebo will be tapered during week 6 (one capsule daily for 7 days), and will be discontinued during week 7 (no capsules for 7 days). Patients will then cross over to receive the alternative treatment (duloxetine), and the sequence will be repeated. Patients will take one capsule of duloxetine daily for 7 days (week 8), two capsules of duloxetine daily for 28 days (weeks 9-12), one capsule of duloxetine daily for 7 days (week 13), and then no capsules for 7 days (week 14).
Measure Participants	67	74
Mean (95% Confidence Interval) [units on a scale]	0.41	1.42

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I/Group A (Duloxetine Then Placebo), Arm II/Group B (Placebo Then Duloxetine)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean difference
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.36 to 1.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse events are assessed during weeks 1-15 of the study.
Adverse Event Reporting Description	The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All graded adverse events are reported. AEs are presented "per sequence" based on how they were collected in the study. The Number of Participants at Risk include subjects who received an intervention, did not have incomplete AE data during primary analysis, and did not withdraw consent prior to receiving the intervention.
Arm/Group Title	Arm I/Group A (Duloxetine Then Placebo)		Arm II/Group B (Placebo Then Duloxetine)
Arm/Group Description	Patients will take one capsule of 30 mg duloxetine orally daily for 7 days (week 1), and then increase to two capsules of duloxetine (60 mg duloxetine) orally daily for 28 days (weeks 2-5). Duloxetine will be tapered during week 6 (one capsule daily for 7 days), and will be discontinued during week 7 (no capsules for 7 days). Patients will then cross over to receive the alternative treatment (placebo), and the sequence will be repeated. Patients will take one capsule of placebo daily for 7 days (week 8), two capsules of placebo daily for 28 days (weeks 9-12), one capsule of placebo daily for 7 days (week 13), and then no capsules for 7 days (week 14).		Patients will take one capsule of placebo orally daily for 7 days (week 1), and then increase to two capsules of placebo orally daily for 28 days (weeks 2-5). Placebo will be tapered during week 6 (one capsule daily for 7 days), and will be discontinued during week 7 (no capsules for 7 days). Patients will then cross over to receive the alternative treatment (duloxetine), and the sequence will be repeated. Patients will take one capsule of duloxetine daily for 7 days (week 8), two capsules of duloxetine daily for 28 days (weeks 9-12), one capsule of duloxetine daily for 7 days (week 13), and then no capsules for 7 days (week 14).
All Cause Mortality
	Arm I/Group A (Duloxetine Then Placebo)		Arm II/Group B (Placebo Then Duloxetine)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I/Group A (Duloxetine Then Placebo)		Arm II/Group B (Placebo Then Duloxetine)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/108 (0.9%)		3/107 (2.8%)
Gastrointestinal disorders
Diarrhea	0/108 (0%)	0	2/107 (1.9%)	2
Vomiting	0/108 (0%)	0	1/107 (0.9%)	1
General disorders
Fatigue	0/108 (0%)	0	1/107 (0.9%)	1
Injury, poisoning and procedural complications
Vascular access complication	0/108 (0%)	0	1/107 (0.9%)	1
Metabolism and nutrition disorders
Anorexia	0/108 (0%)	0	1/107 (0.9%)	1
Nervous system disorders
Dizziness	0/108 (0%)	0	1/107 (0.9%)	1
Headache	1/108 (0.9%)	1	1/107 (0.9%)	1
Peripheral sensory neuropathy	0/108 (0%)	0	1/107 (0.9%)	1
Psychiatric disorders
Insomnia	1/108 (0.9%)	1	1/107 (0.9%)	1
Other (Not Including Serious) Adverse Events
	Arm I/Group A (Duloxetine Then Placebo)		Arm II/Group B (Placebo Then Duloxetine)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	93/108 (86.1%)		91/107 (85%)
Blood and lymphatic system disorders
Hemoglobin decreased	1/108 (0.9%)	1	1/107 (0.9%)	1
Cardiac disorders
Atrial fibrillation	0/108 (0%)	0	1/107 (0.9%)	1
Ear and labyrinth disorders
Tinnitus	1/108 (0.9%)	2	0/107 (0%)	0
Eye disorders
Eye disorder	0/108 (0%)	0	1/107 (0.9%)	4
Vision blurred	2/108 (1.9%)	2	0/107 (0%)	0
Gastrointestinal disorders
Abdominal distension	0/108 (0%)	0	1/107 (0.9%)	1
Abdominal pain	1/108 (0.9%)	1	1/107 (0.9%)	1
Constipation	29/108 (26.9%)	84	32/107 (29.9%)	96
Diarrhea	28/108 (25.9%)	59	31/107 (29%)	103
Dry mouth	24/108 (22.2%)	116	27/107 (25.2%)	146
Dyspepsia	3/108 (2.8%)	3	1/107 (0.9%)	7
Esophagitis	0/108 (0%)	0	1/107 (0.9%)	4
Gastritis	0/108 (0%)	0	1/107 (0.9%)	1
Nausea	50/108 (46.3%)	88	40/107 (37.4%)	82
Stomach pain	1/108 (0.9%)	1	1/107 (0.9%)	3
Vomiting	6/108 (5.6%)	6	4/107 (3.7%)	4
General disorders
Chest pain	0/108 (0%)	0	1/107 (0.9%)	1
Edema limbs	2/108 (1.9%)	6	1/107 (0.9%)	2
Fatigue	56/108 (51.9%)	205	50/107 (46.7%)	297
Fever	0/108 (0%)	0	1/107 (0.9%)	1
Flu-like symptoms	0/108 (0%)	0	1/107 (0.9%)	1
Irritability	1/108 (0.9%)	1	0/107 (0%)	0
Pain	3/108 (2.8%)	9	3/107 (2.8%)	11
Infections and infestations
Bladder infection	1/108 (0.9%)	1	0/107 (0%)	0
Infection	0/108 (0%)	0	1/107 (0.9%)	1
Peripheral nerve infection	0/108 (0%)	0	1/107 (0.9%)	1
Pharyngitis	1/108 (0.9%)	1	0/107 (0%)	0
Upper respiratory infection	1/108 (0.9%)	1	0/107 (0%)	0
Urinary tract infection	1/108 (0.9%)	1	0/107 (0%)	0
Injury, poisoning and procedural complications
Wound dehiscence	1/108 (0.9%)	2	0/107 (0%)	0
Investigations
Alkaline phosphatase increased	0/108 (0%)	0	1/107 (0.9%)	1
Aspartate aminotransferase increased	1/108 (0.9%)	1	1/107 (0.9%)	1
Creatinine increased	2/108 (1.9%)	4	1/107 (0.9%)	1
Laboratory test abnormal	1/108 (0.9%)	1	0/107 (0%)	0
Leukocyte count decreased	0/108 (0%)	0	1/107 (0.9%)	1
Neutrophil count decreased	0/108 (0%)	0	1/107 (0.9%)	1
Platelet count decreased	1/108 (0.9%)	2	1/107 (0.9%)	1
Serum cholesterol increased	0/108 (0%)	0	1/107 (0.9%)	1
Metabolism and nutrition disorders
Anorexia	16/108 (14.8%)	26	23/107 (21.5%)	83
Blood glucose increased	4/108 (3.7%)	7	2/107 (1.9%)	16
Dehydration	2/108 (1.9%)	3	1/107 (0.9%)	1
Serum albumin decreased	2/108 (1.9%)	2	1/107 (0.9%)	1
Serum magnesium decreased	0/108 (0%)	0	1/107 (0.9%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/108 (0.9%)	1	3/107 (2.8%)	30
Arthritis	0/108 (0%)	0	1/107 (0.9%)	1
Back pain	0/108 (0%)	0	4/107 (3.7%)	9
Bone pain	1/108 (0.9%)	1	2/107 (1.9%)	11
Myalgia	1/108 (0.9%)	1	0/107 (0%)	0
Pain in extremity	3/108 (2.8%)	20	7/107 (6.5%)	58
Nervous system disorders
Ataxia	1/108 (0.9%)	1	0/107 (0%)	0
Depressed level of consciousness	12/108 (11.1%)	33	23/107 (21.5%)	69
Dizziness	24/108 (22.2%)	56	19/107 (17.8%)	49
Dysgeusia	0/108 (0%)	0	1/107 (0.9%)	1
Extrapyramidal disorder	0/108 (0%)	0	1/107 (0.9%)	5
Headache	29/108 (26.9%)	74	28/107 (26.2%)	97
Memory impairment	1/108 (0.9%)	2	0/107 (0%)	0
Neuralgia	5/108 (4.6%)	22	3/107 (2.8%)	17
Peripheral motor neuropathy	3/108 (2.8%)	14	3/107 (2.8%)	26
Peripheral sensory neuropathy	21/108 (19.4%)	166	26/107 (24.3%)	205
Syncope	1/108 (0.9%)	1	0/107 (0%)	0
Syncope vasovagal	0/108 (0%)	0	1/107 (0.9%)	1
Psychiatric disorders
Agitation	0/108 (0%)	0	1/107 (0.9%)	1
Anxiety	1/108 (0.9%)	1	1/107 (0.9%)	2
Depression	2/108 (1.9%)	2	1/107 (0.9%)	1
Insomnia	39/108 (36.1%)	167	40/107 (37.4%)	223
Renal and urinary disorders
Glomerular filtration rate decreased	2/108 (1.9%)	5	0/107 (0%)	0
Urinary frequency	1/108 (0.9%)	1	1/107 (0.9%)	1
Reproductive system and breast disorders
Breast pain	1/108 (0.9%)	1	2/107 (1.9%)	2
Ejaculation disorder	1/108 (0.9%)	1	0/107 (0%)	0
Erectile dysfunction	1/108 (0.9%)	1	0/107 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/108 (0%)	0	1/107 (0.9%)	1
Dyspnea	0/108 (0%)	0	1/107 (0.9%)	2
Pharyngolaryngeal pain	1/108 (0.9%)	1	0/107 (0%)	0
Voice alteration	1/108 (0.9%)	1	1/107 (0.9%)	1
Skin and subcutaneous tissue disorders
Dry skin	1/108 (0.9%)	1	0/107 (0%)	0
Erythema multiforme	1/108 (0.9%)	4	0/107 (0%)	0
Pruritus	1/108 (0.9%)	1	2/107 (1.9%)	2
Rash acneiform	0/108 (0%)	0	1/107 (0.9%)	1
Rash desquamating	1/108 (0.9%)	1	2/107 (1.9%)	2
Sweating	2/108 (1.9%)	2	3/107 (2.8%)	5
Vascular disorders
Flushing	0/108 (0%)	0	1/107 (0.9%)	1
Hot flashes	4/108 (3.7%)	13	4/107 (3.7%)	23
Hypertension	2/108 (1.9%)	2	3/107 (2.8%)	7
Hypotension	0/108 (0%)	0	1/107 (0.9%)	2
Vascular disorder	0/108 (0%)	0	1/107 (0.9%)	1

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.