S1115: Selumetinib and Akt Inhibitor MK2206 or mFOLFOX Therapy Comprising Oxaliplatin and Fluorouracil in Treating Patients With Metastatic Pancreatic Cancer Previously Treated With Chemotherapy

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01658943
• Collaborator: (none)
• Enrollment: 137
• Locations: 534
• Arms: 2
• Duration (Months): 34
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well selumetinib and Akt inhibitor MK2206 work compared to modified fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX) therapy in treating patients with metastatic pancreatic cancer previously treated with chemotherapy. Selumetinib and Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet know whether selumetinib and Akt inhibitor MK2206 are more effective than oxaliplatin and fluorouracil in treating patients with metastatic pancreatic cancer.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Acinar Cell Carcinoma; Pancreatic Ductal Adenocarcinoma; Recurrent Pancreatic Carcinoma; Stage IV Pancreatic Cancer	Drug: Akt Inhibitor MK2206; Drug: Fluorouracil; Drug: Oxaliplatin; Drug: Selumetinib	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess overall survival in patients with metastatic pancreatic cancer treated with the combination of AZD6244 hydrogen sulfate (selumetinib) and MK-2206 (Akt inhibitor MK2206) compared to those treated with mFOLFOX.

SECONDARY OBJECTIVES:

1. To assess the frequency and severity of toxicity associated with the combination of AZD6244 hydrogen sulfate and MK-2206 compared to those with mFOLFOX in this patient population.

TERTIARY OBJECTIVES:

1. To assess progression free survival (PFS) in patients with metastatic pancreatic cancer treated with the combination of AZD6244 hydrogen sulfate and MK-2206 compared to those treated with mFOLFOX.

2. To assess objective tumor response in the subset of patients with measurable disease (confirmed and unconfirmed complete and partial response) in patients with metastatic pancreatic cancer treated with the combination of AZD6244 hydrogen sulfate and MK-2206 compared to those treated with mFOLFOX.

3. To bank tissue and blood for future translational medicine studies.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oxaliplatin intravenously (IV) over 2 hours on days 1 and 15 and fluorouracil IV over 46-48 hours on days 1-2 and 15-16 (mFOLFOX).

ARM II: Patients receive Akt inhibitor MK2206 orally (PO) on days 1, 8, 15, and 22, and selumetinib PO daily on days 1-28.

In all arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for up to 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 137 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Clinical Trial of AZD6244 Hydrogen Sulfate (NSC-748727) and MK-2206 (NSC-749607) vs mFOLFOX in Patients With Metastatic Pancreatic Cancer After Prior Chemotherapy
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (mFOLFOX regimen) Patients receive oxaliplatin IV over 2 hours on days 1 and 15 and fluorouracil IV over 46-48 hours on days 1-2 and 15-16.	Drug: Fluorouracil; Given IV; Other Names: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-FU AccuSite Actino-Hermal Adrucil Arumel Cytosafe Efudex Efurix Fiverocil Fluoro Uracil Fluoroplex Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Flurox Ribofluor Ro 2-9757 Ro-2-9757 Timazin ; Drug: Oxaliplatin; Given IV; Other Names: 1-OHP Dacotin Dacplat Diaminocyclohexane Oxalatoplatinum Eloxatin Eloxatine JM-83 Oxalatoplatin Oxalatoplatinum RP 54780 RP-54780 SR-96669
Experimental: Arm II (Akt inhibitor MK2206 and selumetinib) Patients receive Akt inhibitor MK2206 PO on days 1, 8, 15, and 22, and selumetinib PO daily on days 1-28.	Drug: Akt Inhibitor MK2206; Given PO; Other Names: MK2206 ; Drug: Selumetinib; Given PO; Other Names: ARRY-142886 AZD6244 MEK Inhibitor AZD6244

Outcome Measures

Primary Outcome Measures

1. Overall Survival [Up to 3 years]

   From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Secondary Outcome Measures

1. Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [Up to 3 years]

   Only adverse events that are possibly, probably or definitely related to study drug are reported.

Other Outcome Measures

1. Progression-free Survival [Up to 3 years]

   From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.

2. Objective Response Rate [Up to 3 years]

   Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma; patients with endocrine or neuroendocrine tumors, lymphoma of the pancreas, or ampullary cancer are not eligible

• Patients must have distant metastatic disease; patients with macroscopic residual disease post-resection as the only site of disease are not eligible; patient must not have clinically significant ascites (defined as requiring paracentesis) or have brain metastases

• Patients must have received one line, and no more than one line, of prior gemcitabine-based chemotherapy for advanced/metastatic pancreatic cancer and must have documentation of metastatic disease progression while on this treatment; documented disease progression must occur within 42 days of the last treatment; OR

• For patients who received one line of gemcitabine-based chemotherapy for treatment in the adjuvant setting, recurrence to a metastatic site must be documented by imaging studies within 6 months of completing chemotherapy; chemoradiation as part of adjuvant treatment is acceptable; if the patient received one line of adjuvant gemcitabine-based treatment and had disease recurrence after 6 months of completing chemotherapy, patients will only be eligible after failing one additional line of gemcitabine-based chemotherapy used to treat the metastatic disease

• Patients must have measurable and/or non-measurable disease; x-rays, scans. or physical examinations for assessment of measurable disease must have been completed within 28 days prior to registration; x-rays, scans, or other tests for assessment of non-measurable disease must have been completed within 42 days prior to registration; all disease must be assessed and documented on the Baseline Tumor Assessment Form

• Patients must have completed systemic therapy at least 14 days prior to registration, any surgical procedure must have been performed at least 14 days prior to registration, and radiation therapy must be completed at least 7 days prior to registration; patients must have recovered to =< grade 1 from any of the effects of prior therapies or procedures

• Patients must not plan to receive concurrent chemotherapy, radiotherapy, agents known to prolong corrected QT (QTc) interval, or agents known to be strong inducers or inhibitors of cytochrome P450 3A4/5 (CYP3A4/5) or cytochrome P450 1A2 (CYP1A2)

• Patient must not have received prior treatment with fluorouracil, irinotecan, leucovorin calcium, and oxaliplatin (FOLFIRINOX), FOLFOX, oxaliplatin-based chemotherapy, mitogen-activated protein kinase (MEK) inhibitors, phosphoinositide-3-kinase (PI3K) inhibitors, or protein kinase B (AKT) inhibitors

• Zubrod performance status of 0-1

• Leukocytes >= 3,000/mcL

• Absolute neutrophil count (ANC) >= 1,500/mcL

• Platelets >= 100,000/mcL

• Hemoglobin >= 9.0 g/dL

• Patients must have adequate kidney function as evidenced by at least ONE of the following:

• Serum creatinine =< 1.5 mg/dL within 14 days prior to registration

• Calculated creatinine clearance >= 60 mL/min; the serum creatinine value used in the calculation must have been obtained within 14 days prior to registration

• Total bilirubin =< 1.5 times institutional upper limit of normal(IULN)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 2.5 times IULN

• Patients must have an albumin level >= 3.0 g/dL within 14 days prior to registration

• Patients must have an International Normalized Ratio (INR) =< 1.5 times IULN within 14 days prior to registration

• Patients must have an electrocardiogram (ECG) within 14 days prior to registration; patients must have QTcF (by Fridericia's calculation) =< 450 msec (male) or =< 470 msec (female)

• Patients with baseline neuropathy must be =< grade 1 according to Common Terminology Criteria for Adverse Events (CTCAE) v 4.0

• Patients must not have uncontrolled diarrhea or active infection requiring antibiotics and be fully recovered from any previous serious infections within 7 days prior to registration

• Patients must be able to swallow tablets and capsules

• Patients with diabetes must be well controlled with fasting glucose =< grade 1 according to CTCAE v 4.0 within 14 days prior to registration

• Patients with history of congestive heart failure must have an ejection fraction >= 55% within 14 days prior to registration

• Patients must not have any of the following: uncontrolled hypertension, acute coronary syndrome within 6 months prior to registration, poorly controlled angina, New York Heart Association class II-IV heart failure, prior or current cardiomyopathy, atrial fibrillation, or severe valvular heart disease

• Patients must not have a current or past history of central serous retinopathy, retinal vein occlusion, retinal detachment, or have uncontrolled glaucoma (irrespective of intraocular pressure [IOP])

• No prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for five years

• Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method during the study plus at least 16 weeks after last dose; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

• Prestudy history and physical must be obtained within 28 days prior to registration

• Sites must seek additional patient consent for the future use of specimens

• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

• As part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the system

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona	United States	85704
2	The University of Arizona Cancer Center-North Campus	Tucson	Arizona	United States	85719
3	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Kaiser Permanente-Anaheim	Anaheim	California	United States	92807
5	Kaiser Permanente-Deer Valley Medical Center	Antioch	California	United States	94531
6	Kaiser Permanente-Baldwin Park	Baldwin Park	California	United States	91706
7	Kaiser Permanente-Bellflower	Bellflower	California	United States	90706
8	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
9	Mills - Peninsula Hospitals	Burlingame	California	United States	94010
10	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
11	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California	United States	94546
12	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
13	Epic Care-Dublin	Dublin	California	United States	94568
14	Bay Area Breast Surgeons Inc	Emeryville	California	United States	94608
15	Epic Care Partners in Cancer Care	Emeryville	California	United States	94608
16	Kaiser Permanente Hospital	Fontana	California	United States	92335
17	Kaiser Permanente-Fremont	Fremont	California	United States	94538
18	Valley Medical Oncology Consultants-Fremont	Fremont	California	United States	94538
19	Kaiser Permanente	Fresno	California	United States	93720
20	Saint Jude Medical Center	Fullerton	California	United States	92835
21	Kaiser Permanente - Harbor City	Harbor City	California	United States	90710
22	Kaiser Permanente-Irvine	Irvine	California	United States	92618
23	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
24	Los Angeles County-USC Medical Center	Los Angeles	California	United States	90033
25	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
26	Kaiser Permanente-Cadillac	Los Angeles	California	United States	90034
27	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
28	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
29	Fremont - Rideout Cancer Center	Marysville	California	United States	95901
30	Mercy UC Davis Cancer Center	Merced	California	United States	95340
31	Kaiser Permanente-Modesto	Modesto	California	United States	95356
32	El Camino Hospital	Mountain View	California	United States	94040
33	Sutter Cancer Research Consortium	Novato	California	United States	94945
34	Highland General Hospital	Oakland	California	United States	94602
35	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
36	Bay Area Tumor Institute	Oakland	California	United States	94609
37	Hematology and Oncology Associates-Oakland	Oakland	California	United States	94609
38	Tom K Lee Inc	Oakland	California	United States	94609
39	Kaiser Permanente-Oakland	Oakland	California	United States	94611
40	Saint Joseph Hospital - Orange	Orange	California	United States	92868
41	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
42	Kaiser Permanente - Panorama City	Panorama City	California	United States	91402
43	East Bay Medical Oncology Hematology Medical Associates Inc-Pleasant Hill	Pleasant Hill	California	United States	94523
44	Valley Medical Oncology Consultants	Pleasanton	California	United States	94588
45	Kaiser Permanente-Redwood City	Redwood City	California	United States	94063
46	Kaiser Permanente-Richmond	Richmond	California	United States	94801
47	Kaiser Permanente-Riverside	Riverside	California	United States	92505
48	Kaiser Permanente-Roseville	Roseville	California	United States	95661
49	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
50	Kaiser Permanente-South Sacramento	Sacramento	California	United States	95823
51	Kaiser Permanente - Sacramento	Sacramento	California	United States	95825
52	Saint Helena Hospital	Saint Helena	California	United States	94574
53	Kaiser Permanente-San Diego Mission	San Diego	California	United States	92108
54	Kaiser Permanente-San Diego Zion	San Diego	California	United States	92120
55	Kaiser Permanente-San Francisco	San Francisco	California	United States	94115
56	California Pacific Medical Center-Pacific Campus	San Francisco	California	United States	94118
57	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California	United States	95119
58	Kaiser Permanente San Leandro	San Leandro	California	United States	94577
59	Kaiser Permanente-San Marcos	San Marcos	California	United States	92069
60	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California	United States	94806
61	Kaiser Permanente-San Rafael	San Rafael	California	United States	94903
62	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
63	Kaiser Permanente-Santa Rosa	Santa Rosa	California	United States	95403
64	Sutter Pacific Medical Foundation	Santa Rosa	California	United States	95403
65	Kaiser Permanente-South San Francisco	South San Francisco	California	United States	94080
66	Kaiser Permanente-Stockton	Stockton	California	United States	95210
67	Tahoe Forest Cancer Center	Truckee	California	United States	96161
68	Kaiser Permanente Medical Center-Vacaville	Vacaville	California	United States	95688
69	Kaiser Permanente-Vallejo	Vallejo	California	United States	94589
70	Sutter Solano Medical Center/Cancer Center	Vallejo	California	United States	94589
71	Kaiser Permanente-Walnut Creek	Walnut Creek	California	United States	94596
72	Kaiser Permanente	Woodland Hills	California	United States	91367
73	The Medical Center of Aurora	Aurora	Colorado	United States	80012
74	Boulder Community Hospital	Boulder	Colorado	United States	80301
75	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado	United States	80304
76	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
77	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado	United States	80907
78	Kaiser Permanente-Franklin	Denver	Colorado	United States	80205
79	Porter Adventist Hospital	Denver	Colorado	United States	80210
80	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
81	Exempla Saint Joseph Hospital	Denver	Colorado	United States	80218
82	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
83	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado	United States	80218
84	Rocky Mountain Cancer Centers-Rose	Denver	Colorado	United States	80220
85	Rose Medical Center	Denver	Colorado	United States	80220
86	Colorado Cancer Research Program CCOP	Denver	Colorado	United States	80224-2522
87	Mercy Medical Center	Durango	Colorado	United States	81301
88	Comprehensive Cancer Care and Research Institute of Colorado LLC	Englewood	Colorado	United States	80113
89	Swedish Medical Center	Englewood	Colorado	United States	80113
90	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
91	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
92	Mountain Blue Cancer Care Center	Golden	Colorado	United States	80401
93	North Colorado Medical Center	Greeley	Colorado	United States	80631
94	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado	United States	80111
95	Kaiser Permanente-Rock Creek	Lafayette	Colorado	United States	80026
96	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado	United States	80228
97	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
98	Littleton Adventist Hospital	Littleton	Colorado	United States	80122
99	Kaiser Permanente-Lone Tree	Lone Tree	Colorado	United States	80124
100	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado	United States	80124
101	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
102	Longmont United Hospital	Longmont	Colorado	United States	80501
103	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado	United States	80501
104	McKee Medical Center	Loveland	Colorado	United States	80539
105	Parker Adventist Hospital	Parker	Colorado	United States	80138
106	Rocky Mountain Cancer Centers-Parker	Parker	Colorado	United States	80138
107	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
108	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado	United States	81008
109	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
110	Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
111	Middlesex Hospital	Middletown	Connecticut	United States	06457
112	Stamford Hospital/Bennett Cancer Center	Stamford	Connecticut	United States	06904
113	Beebe Medical Center	Lewes	Delaware	United States	19958
114	Christiana Gynecologic Oncology LLC	Newark	Delaware	United States	19713
115	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware	United States	19713
116	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
117	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
118	Regional Hematology and Oncology PA	Newark	Delaware	United States	19713
119	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
120	Beebe Health Campus	Rehoboth Beach	Delaware	United States	19971
121	Nanticoke Memorial Hospital	Seaford	Delaware	United States	19973
122	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware	United States	19801
123	Baptist Cancer Institute	Jacksonville	Florida	United States	32207
124	Florida Hospital Orlando	Orlando	Florida	United States	32803
125	University Cancer and Blood Center LLC	Athens	Georgia	United States	30607
126	Georgia Regents University Medical Center	Augusta	Georgia	United States	30912
127	Dekalb Medical Center	Decatur	Georgia	United States	30033
128	Northeast Georgia Medical Center	Gainesville	Georgia	United States	30501
129	Medical Center of Central Georgia	Macon	Georgia	United States	31208
130	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia	United States	31405
131	South Georgia Medical Center	Valdosta	Georgia	United States	31603
132	Oncare Hawaii Inc-Pali Momi	Aiea	Hawaii	United States	96701
133	Pali Momi Medical Center	Aiea	Hawaii	United States	96701
134	Oncare Hawaii Inc-POB II	Honolulu	Hawaii	United States	96813
135	Queen's Medical Center	Honolulu	Hawaii	United States	96813
136	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
137	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
138	OnCare Hawaii-Liliha	Honolulu	Hawaii	United States	96817-3169
139	Oncare Hawaii Inc-Kuakini	Honolulu	Hawaii	United States	96817
140	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii	United States	96819
141	Castle Medical Center	Kailua	Hawaii	United States	96734
142	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii	United States	96766
143	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
144	Idaho Urologic Institute-Meridian	Meridian	Idaho	United States	83642
145	Kootenai Cancer Center	Post Falls	Idaho	United States	83854
146	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
147	Memorial Hospital of Carbondale	Carbondale	Illinois	United States	62902
148	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
149	Northwestern University	Chicago	Illinois	United States	60611
150	Rush University Medical Center	Chicago	Illinois	United States	60612
151	University of Illinois	Chicago	Illinois	United States	60612
152	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
153	Weiss Memorial Hospital	Chicago	Illinois	United States	60640
154	Cancer Care Center of Decatur	Decatur	Illinois	United States	62526
155	Central Illinois CCOP	Decatur	Illinois	United States	62526
156	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
157	Crossroads Cancer Center	Effingham	Illinois	United States	62401
158	Advocate Sherman Hospital	Elgin	Illinois	United States	60123
159	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
160	Hematology Oncology Associates of Illinois-Highland Park	Highland Park	Illinois	United States	60035
161	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois	United States	60435
162	Presence Saint Mary's Hospital	Kankakee	Illinois	United States	60901
163	NorthShore Hematology Oncology-Libertyville	Libertyville	Illinois	United States	60048
164	Loyola University Medical Center	Maywood	Illinois	United States	60153
165	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
166	Illinois Cancer Specialists-Niles	Niles	Illinois	United States	60714
167	West Suburban Medical Center	River Forest	Illinois	United States	60305
168	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois	United States	60076
169	Memorial Medical Center	Springfield	Illinois	United States	62781
170	Carle Cancer Center	Urbana	Illinois	United States	61801
171	Franciscan St. Francis Health-Beech Grove	Beech Grove	Indiana	United States	46107
172	Elkhart Clinic	Elkhart	Indiana	United States	46514-2098
173	Michiana Hematology Oncology PC-Elkhart	Elkhart	Indiana	United States	46514
174	Elkhart General Hospital	Elkhart	Indiana	United States	46515
175	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
176	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
177	IU Health Central Indiana Cancer Centers-East	Indianapolis	Indiana	United States	46219
178	Franciscan Saint Francis Health-Indianapolis	Indianapolis	Indiana	United States	46237
179	Community Howard Regional Health	Kokomo	Indiana	United States	46904
180	IU Health La Porte Hospital	La Porte	Indiana	United States	46350
181	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana	United States	46360
182	Cancer Care Partners LLC	Mishawaka	Indiana	United States	46545
183	Michiana Hematology Oncology PC-Mishawaka	Mishawaka	Indiana	United States	46545
184	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545
185	Michiana Hematology Oncology PC-Plymouth	Plymouth	Indiana	United States	46563
186	Reid Hospital and Health Care Services	Richmond	Indiana	United States	47374
187	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
188	Michiana Hematology Oncology PC-South Bend	South Bend	Indiana	United States	46601
189	South Bend Clinic	South Bend	Indiana	United States	46617
190	Northern Indiana Cancer Research Consortium CCOP	South Bend	Indiana	United States	46628
191	Michiana Hematology Oncology PC-Westville	Westville	Indiana	United States	46391
192	Hematology Oncology Associates-Quad Cities	Bettendorf	Iowa	United States	52722
193	Genesis Medical Center - East Campus	Davenport	Iowa	United States	52803
194	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
195	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51104
196	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
197	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
198	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
199	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
200	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
201	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
202	Providence Medical Center	Kansas City	Kansas	United States	66112
203	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
204	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
205	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67901
206	Cancer Center of Kansas-Manhattan	Manhattan	Kansas	United States	66502
207	Cancer Center of Kansas - McPherson	McPherson	Kansas	United States	67460
208	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
209	Menorah Medical Center	Overland Park	Kansas	United States	66209
210	Saint Luke's South Hospital	Overland Park	Kansas	United States	66213
211	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
212	Kansas City CCOP	Prairie Village	Kansas	United States	66208
213	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
214	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
215	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
216	Associates In Womens Health	Wichita	Kansas	United States	67208
217	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
218	Cancer Center of Kansas - Main Office	Wichita	Kansas	United States	67214
219	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
220	Wichita CCOP	Wichita	Kansas	United States	67214
221	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
222	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky	United States	41017
223	Hematology/Oncology Clinic LLP	Baton Rouge	Louisiana	United States	70809
224	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana	United States	70809
225	Ochsner Health Center-Summa	Baton Rouge	Louisiana	United States	70809
226	Cancer Center of Acadiana	Lafayette	Louisiana	United States	70503
227	DeSoto Regional Health System	Mansfield	Louisiana	United States	71052
228	University Health-Conway	Monroe	Louisiana	United States	71202
229	Louisiana State University Health Science Center	New Orleans	Louisiana	United States	70112
230	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
231	Ochsner Baptist Medical Center	New Orleans	Louisiana	United States	70115
232	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
233	Louisiana State University Health Sciences Center Shreveport	Shreveport	Louisiana	United States	71103
234	Highland Clinic	Shreveport	Louisiana	United States	71105
235	Harold Alfond Center for Cancer Care	Augusta	Maine	United States	04330
236	Eastern Maine Medical Center	Bangor	Maine	United States	04401
237	Union Hospital of Cecil County	Elkton MD	Maryland	United States	21921
238	Bixby Medical Center	Adrian	Michigan	United States	49221
239	Hickman Cancer Center	Adrian	Michigan	United States	49221
240	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
241	Michigan Cancer Research Consortium CCOP	Ann Arbor	Michigan	United States	48106
242	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
243	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
244	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan	United States	49307
245	Huron Valley-Sinai Hospital	Commerce	Michigan	United States	48382
246	Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48124
247	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
248	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
249	Hurley Medical Center	Flint	Michigan	United States	48502
250	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
251	Genesys Regional Medical Center	Grand Blanc	Michigan	United States	48439
252	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan	United States	49503
253	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
254	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
255	Allegiance Health	Jackson	Michigan	United States	49201
256	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
257	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
258	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
259	Sparrow Hospital	Lansing	Michigan	United States	48912
260	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
261	Mercy Memorial Hospital	Monroe	Michigan	United States	48162
262	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan	United States	48162
263	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
264	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
265	Saint Joseph Mercy Port Huron	Port Huron	Michigan	United States	48060
266	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
267	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
268	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
269	Providence Hospital-Southfield Cancer Center	Southfield	Michigan	United States	48075
270	Lakeland Hospital	St. Joseph	Michigan	United States	49085
271	Munson Medical Center	Traverse City	Michigan	United States	49684
272	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
273	Sanford Clinic North-Bemidgi	Bemidji	Minnesota	United States	56601
274	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
275	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
276	Fairview-Southdale Hospital	Edina	Minnesota	United States	55435
277	Unity Hospital	Fridley	Minnesota	United States	55432
278	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
279	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
280	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
281	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
282	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
283	New Ulm Medical Center	New Ulm	Minnesota	United States	56073
284	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
285	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota	United States	56303
286	Saint Cloud Hospital	Saint Cloud	Minnesota	United States	56303
287	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
288	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
289	Regions Hospital	Saint Paul	Minnesota	United States	55101
290	United Hospital	Saint Paul	Minnesota	United States	55102
291	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
292	Lakeview Hospital	Stillwater	Minnesota	United States	55082
293	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
294	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
295	Minnesota Oncology and Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
296	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
297	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
298	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
299	University of Missouri - Ellis Fischel	Columbia	Missouri	United States	65212
300	Centerpoint Medical Center LLC	Independence	Missouri	United States	64057
301	Capital Region Medical Center-Goldschmidt Cancer Center	Jefferson City	Missouri	United States	65109
302	Saint Luke's Hospital of Kansas City	Kansas City	Missouri	United States	64111
303	North Kansas City Hospital	Kansas City	Missouri	United States	64116
304	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri	United States	64118
305	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri	United States	64128
306	Research Medical Center	Kansas City	Missouri	United States	64132
307	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
308	Liberty Radiation Oncology Center	Liberty	Missouri	United States	64068
309	Phelps County Regional Medical Center	Rolla	Missouri	United States	65401
310	Saint John's Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
311	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
312	Saint Joseph Oncology Inc	Saint Joseph	Missouri	United States	64507
313	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
314	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
315	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
316	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
317	Cancer Research for the Ozarks NCORP	Springfield	Missouri	United States	65804
318	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
319	CoxHealth South Hospital	Springfield	Missouri	United States	65807
320	Montana Cancer Consortium NCORP	Billings	Montana	United States	59101
321	Saint Vincent Healthcare	Billings	Montana	United States	59101
322	Frontier Cancer Center and Blood Institute-Billings	Billings	Montana	United States	59102
323	Billings Clinic Cancer Center	Billings	Montana	United States	59107
324	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
325	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
326	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
327	Big Sky Oncology	Great Falls	Montana	United States	59405
328	Saint Peter's Community Hospital	Helena	Montana	United States	59601
329	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
330	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
331	Montana Cancer Specialists	Missoula	Montana	United States	59802
332	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
333	CHI Health Good Samaritan	Kearney	Nebraska	United States	68847
334	Nebraska Cancer Research Center	Lincoln	Nebraska	United States	68510
335	Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
336	Alegent Health Immanuel Medical Center	Omaha	Nebraska	United States	68122
337	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
338	Alegent Health Lakeside Hospital	Omaha	Nebraska	United States	68130
339	Creighton University Medical Center	Omaha	Nebraska	United States	68131
340	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
341	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
342	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
343	Veterans Adminstration New Jersey Health Care System	East Orange	New Jersey	United States	07018-1095
344	AtlantiCare Surgery Center	Egg Harbor Township	New Jersey	United States	08234
345	Englewood Hospital and Medical Center	Englewood	New Jersey	United States	07631
346	UMDNJ - New Jersey Medical School	Newark	New Jersey	United States	07103
347	Albert Einstein College of Medicine	Bronx	New York	United States	10461
348	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467-2490
349	Kings County Hospital	Brooklyn	New York	United States	11203
350	State University of New York Downstate Medical Center	Brooklyn	New York	United States	11203
351	Mary Imogene Bassett Hospital	Cooperstown	New York	United States	13326
352	Glens Falls Hospital	Glens Falls	New York	United States	12801
353	Orange Regional Medical Center	Middletown	New York	United States	10940
354	Winthrop University Hospital	Mineola	New York	United States	11501
355	Columbia University Medical Center	New York	New York	United States	10032
356	University of Rochester	Rochester	New York	United States	14642
357	Staten Island University Hospital	Staten Island	New York	United States	10305
358	Randolph Hospital	Asheboro	North Carolina	United States	27203
359	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
360	Cone Health Cancer Center	Greensboro	North Carolina	United States	27403
361	Kinston Medical Specialists PA	Kinston	North Carolina	United States	28501
362	FirstHealth of the Carolinas-Moore Regional Hosiptal	Pinehurst	North Carolina	United States	28374
363	Annie Penn Memorial Hospital	Reidsville	North Carolina	United States	27320
364	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
365	Southeast Cancer Control Consortium CCOP	Winston-Salem	North Carolina	United States	27104
366	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
367	Saint Alexius Medical Center	Bismarck	North Dakota	United States	58501
368	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
369	Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
370	Sanford Clinic North-Fargo	Fargo	North Dakota	United States	58122
371	Sanford Medical Center-Fargo	Fargo	North Dakota	United States	58122
372	Summa Akron City Hospital/Cooper Cancer Center	Akron	Ohio	United States	44304
373	Akron General Medical Center	Akron	Ohio	United States	44307
374	Summa Barberton Hospital	Barberton	Ohio	United States	44203
375	Cleveland Clinic Cancer Center Beachwood	Beachwood	Ohio	United States	44122
376	Strecker Cancer Center-Belpre	Belpre	Ohio	United States	45714
377	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio	United States	43402
378	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
379	Oncology Hematology Care Inc-Eden Park	Cincinnati	Ohio	United States	45202
380	Oncology Hematology Care Inc-Mercy West	Cincinnati	Ohio	United States	45211
381	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio	United States	45220
382	Oncology Hematology Care Inc - Anderson	Cincinnati	Ohio	United States	45230
383	Oncology Hematology Care Inc - Kenwood	Cincinnati	Ohio	United States	45236
384	Bethesda North Hospital	Cincinnati	Ohio	United States	45242
385	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio	United States	45242
386	Case Western Reserve University	Cleveland	Ohio	United States	44106
387	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
388	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
389	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
390	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
391	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio	United States	43214
392	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
393	Columbus CCOP	Columbus	Ohio	United States	43215
394	Grant Medical Center	Columbus	Ohio	United States	43215
395	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
396	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
397	Doctors Hospital	Columbus	Ohio	United States	43228
398	Grandview Hospital	Dayton	Ohio	United States	45405
399	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
400	Miami Valley Hospital	Dayton	Ohio	United States	45409
401	Samaritan North Health Center	Dayton	Ohio	United States	45415
402	Dayton CCOP	Dayton	Ohio	United States	45420
403	Delaware Health Center-Grady Cancer Center	Delaware	Ohio	United States	43015
404	Delaware Radiation Oncology	Delaware	Ohio	United States	43015
405	Grady Memorial Hospital	Delaware	Ohio	United States	43015
406	Hematology Oncology Center Incorporated	Elyria	Ohio	United States	44035
407	Mercy Cancer Center-Elyria	Elyria	Ohio	United States	44035
408	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio	United States	45014
409	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
410	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
411	Wayne Hospital	Greenville	Ohio	United States	45331
412	Kettering Medical Center	Kettering	Ohio	United States	45429
413	Fairfield Medical Center	Lancaster	Ohio	United States	43130
414	Lancaster Radiation Oncology	Lancaster	Ohio	United States	43130
415	Saint Rita's Medical Center	Lima	Ohio	United States	45801
416	Lima Memorial Hospital	Lima	Ohio	United States	45804
417	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
418	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio	United States	43537
419	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio	United States	43537
420	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
421	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
422	Licking Memorial Hospital	Newark	Ohio	United States	43055
423	Newark Radiation Oncology	Newark	Ohio	United States	43055
424	Saint Charles Hospital	Oregon	Ohio	United States	43616
425	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio	United States	43616
426	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
427	North Coast Cancer Care	Sandusky	Ohio	United States	44870
428	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
429	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio	United States	44136
430	Flower Hospital	Sylvania	Ohio	United States	43560
431	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
432	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio	United States	43606
433	Saint Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
434	University of Toledo	Toledo	Ohio	United States	43614
435	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio	United States	43617
436	Mercy Saint Anne Hospital	Toledo	Ohio	United States	43623
437	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
438	Upper Valley Medical Center	Troy	Ohio	United States	45373
439	Fulton County Health Center	Wauseon	Ohio	United States	43567
440	Saint Ann's Hospital	Westerville	Ohio	United States	43081
441	Cleveland Clinic Wooster Specialty Center	Wooster	Ohio	United States	44691
442	Greene Memorial Hospital	Xenia	Ohio	United States	45385
443	Genesis HealthCare System	Zanesville	Ohio	United States	43701
444	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
445	Oklahoma Oncology Inc	Tulsa	Oklahoma	United States	74104
446	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma	United States	74136
447	Warren Cancer Research Foundation	Tulsa	Oklahoma	United States	74136
448	Tulsa Cancer Institute	Tulsa	Oklahoma	United States	74146
449	Legacy Mount Hood Medical Center	Gresham	Oregon	United States	97030
450	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon	United States	97210
451	Legacy Emanuel Hospital and Health Center	Portland	Oregon	United States	97227
452	Legacy Meridian Park Hospital	Tualatin	Oregon	United States	97062
453	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
454	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
455	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
456	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
457	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
458	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
459	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17604
460	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania	United States	17837
461	Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301
462	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
463	Geisinger Medical Oncology-Pottsville	Pottsville	Pennsylvania	United States	17901
464	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania	United States	18840
465	Geisinger Medical Group	State College	Pennsylvania	United States	16801
466	Reading Hospital	West Reading	Pennsylvania	United States	19611
467	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
468	Lankenau Medical Center	Wynnewood	Pennsylvania	United States	19096
469	Mainline Health CCOP	Wynnewood	Pennsylvania	United States	19096
470	Sanford Cancer Center-Oncology Clinic	Sioux Falls	South Dakota	United States	57104
471	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
472	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
473	Erlanger Medical Center	Chattanooga	Tennessee	United States	37403
474	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
475	The Don and Sybil Harrington Cancer Center	Amarillo	Texas	United States	79106
476	Texas Tech University Health Sciences Center	Lubbock	Texas	United States	79430
477	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
478	Danville Hematology Oncology	Danville	Virginia	United States	24541
479	Danville Regional Medical Center	Danville	Virginia	United States	24541
480	Fredericksburg Oncology Inc	Fredericksburg	Virginia	United States	22401
481	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
482	Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
483	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
484	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
485	Highline Medical Center-Main Campus	Burien	Washington	United States	98166
486	Swedish Medical Center-Edmonds	Edmonds	Washington	United States	98026
487	Swedish Cancer Institute-Issaquah	Issaquah	Washington	United States	98029
488	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
489	Seattle Cancer Care Alliance at EvergreenHealth	Kirkland	Washington	United States	98034
490	Skagit Valley Hospital	Mount Vernon	Washington	United States	98274
491	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
492	Harborview Medical Center	Seattle	Washington	United States	98104
493	Minor and James Medical PLLC	Seattle	Washington	United States	98104
494	Swedish Medical Center-Ballard Campus	Seattle	Washington	United States	98107
495	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
496	Group Health Cooperative of Puget Sound Oncology Consortium	Seattle	Washington	United States	98112
497	Group Health Cooperative-Seattle	Seattle	Washington	United States	98112
498	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
499	University of Washington Medical Center	Seattle	Washington	United States	98195
500	United General Hospital	Sedro-Woolley	Washington	United States	98284
501	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
502	Evergreen Hematology and Oncology PS	Spokane	Washington	United States	99218
503	Rockwood Clinic	Spokane	Washington	United States	99220
504	Legacy Salmon Creek Hospital	Vancouver	Washington	United States	98686
505	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
506	West Virginia University Charleston	Charleston	West Virginia	United States	25304
507	West Virginia University Healthcare	Morgantown	West Virginia	United States	26506
508	Langlade Hospital and Cancer Center	Antigo	Wisconsin	United States	54409
509	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
510	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin	United States	54701
511	Sacred Heart Hospital	Eau Claire	Wisconsin	United States	54701
512	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
513	Marshfield Clinic - Ladysmith Center	Ladysmith	Wisconsin	United States	54848
514	Dean Hematology and Oncology Clinic	Madison	Wisconsin	United States	53717
515	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
516	Saint Joseph's Hospital	Marshfield	Wisconsin	United States	54449
517	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
518	D N Greenwald Center	Mukwonago	Wisconsin	United States	53149
519	Cancer Center of Western Wisconsin	New Richmond	Wisconsin	United States	54017
520	Oconomowoc Memorial Hospital-ProHealth Care Inc	Oconomowoc	Wisconsin	United States	53066
521	Marshfield Clinic at James Beck Cancer Center	Rhinelander	Wisconsin	United States	54501
522	Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
523	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin	United States	54868
524	Marshfield Clinic Cancer Care at Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
525	Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
526	Waukesha Memorial Hospital	Waukesha	Wisconsin	United States	53188
527	Aspirus Regional Cancer Center	Wausau	Wisconsin	United States	54401
528	Marshfield Clinic-Wausau Center	Wausau	Wisconsin	United States	54401
529	Diagnostic and Treatment Center	Weston	Wisconsin	United States	54476
530	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
531	Saint Clare's Hospital	Weston	Wisconsin	United States	54476
532	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
533	Rocky Mountain Oncology	Casper	Wyoming	United States	82609
534	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Vincent Chung, Southwest Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01658943
• Other Study ID Numbers: NCI-2012-01993; NCI-2012-01993; SWOG-S1115; CDR0000737878; S1115; S1115; U10CA180888; U10CA032102
• First Posted: Aug 7, 2012
• Last Update Posted: Mar 9, 2016
• Last Verified: Jul 1, 2015

• Additional relevant MeSH terms: Carcinoma; Pancreatic Neoplasms; Carcinoma, Acinar Cell; Fluorouracil; Oxaliplatin

Study Results

Participant Flow

Arm/Group Title	mFOLFOX	MK2206 and Selumetinib
Arm/Group Description	Patients receive 85 mg/m^2 oxaliplatin IV over 2 hours on days 1 and 15 and 2,400 mg/m^2 fluorouracil IV over 46-48 hours on days 1-2 and 15-16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive 135 mg MK2206 PO on days 1, 8, 15, and 22, and 100 mg selumetinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	70	67
Eligible	63	58
Eligible and Began Protocol Therapy	62	58
COMPLETED	0	0
NOT COMPLETED	70	67

Baseline Characteristics

Arm/Group Title	mFOLFOX	MK2206 and Selumetinib	Total
Arm/Group Description	Patients receive 85 mg/m^2 oxaliplatin IV over 2 hours on days 1 and 15 and 2,400 mg/m^2 fluorouracil IV over 46-48 hours on days 1-2 and 15-16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive 135 mg MK2206 PO on days 1, 8, 15, and 22, and 100 mg selumetinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	62	58	120
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65.6	69.4	67.3
Sex: Female, Male (Count of Participants)
Female	40 64.5%	23 39.7%	63 52.5%
Male	22 35.5%	35 60.3%	57 47.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 4.8%	1 1.7%	4 3.3%
Not Hispanic or Latino	59 95.2%	57 98.3%	116 96.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	4 6.5%	4 6.9%	8 6.7%
Native Hawaiian or Other Pacific Islander	1 1.6%	1 1.7%	2 1.7%
Black or African American	7 11.3%	4 6.9%	11 9.2%
White	50 80.6%	49 84.5%	99 82.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Prior Systemic Therapy (participants) [Number]
4 months or less	23 37.1%	22 37.9%	45 37.5%
more than 4 months	39 62.9%	36 62.1%	75 62.5%
Liver Metastasis (participants) [Number]
Yes	39 62.9%	43 74.1%	82 68.3%
No	23 37.1%	15 25.9%	38 31.7%

Outcome Measures

1. Secondary Outcome

Title	Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
Description	Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Eligible patients who received any treatment and were assessed for adverse events are included in this summary.

Arm/Group Title	mFOLFOX	MK2206 and Selumetinib
Arm/Group Description	Patients receive 85 mg/m^2 oxaliplatin IV over 2 hours on days 1 and 15 and 2,400 mg/m^2 fluorouracil IV over 46-48 hours on days 1-2 and 15-16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive 135 mg MK2206 PO on days 1, 8, 15, and 22, and 100 mg selumetinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	62	57
Abdominal pain	1 1.6%	0 0%
Alanine aminotransferase increased	0 0%	4 6.9%
Alkaline phosphatase increased	0 0%	2 3.4%
Anemia	2 3.2%	3 5.2%
Anorexia	1 1.6%	1 1.7%
Aspartate aminotransferase increased	0 0%	3 5.2%
Blood bilirubin increased	1 1.6%	0 0%
Cognitive disturbance	0 0%	1 1.7%
Dehydration	1 1.6%	6 10.3%
Device related infection	1 1.6%	0 0%
Diarrhea	4 6.5%	4 6.9%
Edema face	0 0%	1 1.7%
Encephalopathy	0 0%	1 1.7%
Erythema multiforme	0 0%	1 1.7%
Erythroderma	0 0%	1 1.7%
Fatigue	8 12.9%	7 12.1%
Generalized muscle weakness	0 0%	1 1.7%
Hepatic failure	0 0%	1 1.7%
Hyperglycemia	1 1.6%	7 12.1%
Hypertension	2 3.2%	5 8.6%
Hypokalemia	1 1.6%	1 1.7%
Hypomagnesemia	1 1.6%	0 0%
Hyponatremia	1 1.6%	4 6.9%
Hypophosphatemia	0 0%	1 1.7%
Hypotension	1 1.6%	1 1.7%
Hypoxia	0 0%	1 1.7%
Left ventricular systolic dysfunction	0 0%	1 1.7%
Lung infection	1 1.6%	1 1.7%
Lymphocyte count decreased	8 12.9%	0 0%
Mucositis oral	1 1.6%	4 6.9%
Multi-organ failure	0 0%	1 1.7%
Nausea	3 4.8%	0 0%
Neoplasms benign, malignant and unspecified	0 0%	2 3.4%
Neutrophil count decreased	4 6.5%	0 0%
Platelet count decreased	1 1.6%	0 0%
Rash acneiform	0 0%	5 8.6%
Rash maculo-papular	0 0%	7 12.1%
Skin infection	0 0%	1 1.7%
Soft tissue infection	0 0%	1 1.7%
Stevens-Johnson syndrome	0 0%	1 1.7%
Syncope	0 0%	1 1.7%
Vomiting	3 4.8%	1 1.7%
Weight loss	1 1.6%	0 0%
White blood cell decreased	2 3.2%	0 0%

2. Primary Outcome

Title	Overall Survival
Description	From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Eligible and analyzable patients.

Arm/Group Title	mFOLFOX	MK2206 and Selumetinib
Arm/Group Description	Patients receive 85 mg/m^2 oxaliplatin IV over 2 hours on days 1 and 15 and 2,400 mg/m^2 fluorouracil IV over 46-48 hours on days 1-2 and 15-16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive 135 mg MK2206 PO on days 1, 8, 15, and 22, and 100 mg selumetinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	62	58
Median (95% Confidence Interval) [months]	6.7	3.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	mFOLFOX, MK2206 and Selumetinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Log Rank
	Comments

3. Other Pre-specified Outcome

Title	Progression-free Survival
Description	From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Eligible and analyzable patients.

Arm/Group Title	mFOLFOX	MK2206 and Selumetinib
Arm/Group Description	Patients receive 85 mg/m^2 oxaliplatin IV over 2 hours on days 1 and 15 and 2,400 mg/m^2 fluorouracil IV over 46-48 hours on days 1-2 and 15-16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive 135 mg MK2206 PO on days 1, 8, 15, and 22, and 100 mg selumetinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	62	58
Median (95% Confidence Interval) [months]	2.0	1.9

4. Other Pre-specified Outcome

Title	Objective Response Rate
Description	Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

All eligible and analyzable patients with measurable disease.

Arm/Group Title	mFOLFOX	MK2206 and Selumetinib
Arm/Group Description	Patients receive 85 mg/m^2 oxaliplatin IV over 2 hours on days 1 and 15 and 2,400 mg/m^2 fluorouracil IV over 46-48 hours on days 1-2 and 15-16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive 135 mg MK2206 PO on days 1, 8, 15, and 22, and 100 mg selumetinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	57	55
Partial Response	4 6.5%	0 0%
Unconfirmed Partial Response	1 1.6%	1 1.7%
Stable/No response	14 22.6%	12 20.7%
Increasing disease	29 46.8%	34 58.6%
Symptomatic Deterioration	3 4.8%	2 3.4%
Assessment Inadequate	6 9.7%	6 10.3%

Adverse Events

Time Frame	Up to 3 years
Adverse Event Reporting Description	Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Arm/Group Title	mFOLFOX		MK2206 and Selumetinib
Arm/Group Description	Patients receive 85 mg/m^2 oxaliplatin IV over 2 hours on days 1 and 15 and 2,400 mg/m^2 fluorouracil IV over 46-48 hours on days 1-2 and 15-16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.		Patients receive 135 mg MK2206 PO on days 1, 8, 15, and 22, and 100 mg selumetinib PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	mFOLFOX		MK2206 and Selumetinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	mFOLFOX		MK2206 and Selumetinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/62 (3.2%)		37/57 (64.9%)
Blood and lymphatic system disorders
Anemia	0/62 (0%)		2/57 (3.5%)
Cardiac disorders
Left ventricular systolic dysfunction	0/62 (0%)		1/57 (1.8%)
Myocardial infarction	0/62 (0%)		1/57 (1.8%)
Gastrointestinal disorders
Abdominal distension	0/62 (0%)		1/57 (1.8%)
Abdominal pain	0/62 (0%)		1/57 (1.8%)
Colonic perforation	1/62 (1.6%)		0/57 (0%)
Constipation	0/62 (0%)		2/57 (3.5%)
Diarrhea	0/62 (0%)		3/57 (5.3%)
Duodenal perforation	0/62 (0%)		1/57 (1.8%)
Dysphagia	0/62 (0%)		1/57 (1.8%)
Gastric perforation	0/62 (0%)		1/57 (1.8%)
Mucositis oral	0/62 (0%)		2/57 (3.5%)
Nausea	0/62 (0%)		1/57 (1.8%)
Vomiting	0/62 (0%)		2/57 (3.5%)
General disorders
Fatigue	0/62 (0%)		2/57 (3.5%)
Fever	0/62 (0%)		2/57 (3.5%)
General disorders and admin site conditions - Other	0/62 (0%)		1/57 (1.8%)
Multi-organ failure	0/62 (0%)		1/57 (1.8%)
Hepatobiliary disorders
Hepatic failure	0/62 (0%)		1/57 (1.8%)
Infections and infestations
Infections and infestations-Other	0/62 (0%)		2/57 (3.5%)
Lung infection	1/62 (1.6%)		1/57 (1.8%)
Sepsis	1/62 (1.6%)		2/57 (3.5%)
Skin infection	0/62 (0%)		1/57 (1.8%)
Soft tissue infection	0/62 (0%)		1/57 (1.8%)
Injury, poisoning and procedural complications
Intraoperative gastrointestinal injury	0/62 (0%)		1/57 (1.8%)
Spinal fracture	0/62 (0%)		1/57 (1.8%)
Investigations
Alanine aminotransferase increased	0/62 (0%)		1/57 (1.8%)
Alkaline phosphatase increased	0/62 (0%)		2/57 (3.5%)
Aspartate aminotransferase increased	0/62 (0%)		1/57 (1.8%)
Blood bilirubin increased	0/62 (0%)		2/57 (3.5%)
Investigations-Other	0/62 (0%)		1/57 (1.8%)
Metabolism and nutrition disorders
Anorexia	0/62 (0%)		2/57 (3.5%)
Dehydration	0/62 (0%)		7/57 (12.3%)
Hyperglycemia	0/62 (0%)		5/57 (8.8%)
Hyponatremia	0/62 (0%)		2/57 (3.5%)
Hypophosphatemia	0/62 (0%)		1/57 (1.8%)
Musculoskeletal and connective tissue disorders
Back pain	0/62 (0%)		1/57 (1.8%)
Generalized muscle weakness	0/62 (0%)		3/57 (5.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified - Other	0/62 (0%)		10/57 (17.5%)
Nervous system disorders
Cognitive disturbance	0/62 (0%)		1/57 (1.8%)
Depressed level of consciousness	0/62 (0%)		1/57 (1.8%)
Encephalopathy	0/62 (0%)		1/57 (1.8%)
Stroke	0/62 (0%)		1/57 (1.8%)
Syncope	0/62 (0%)		2/57 (3.5%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/62 (0%)		1/57 (1.8%)
Hypoxia	0/62 (0%)		1/57 (1.8%)
Skin and subcutaneous tissue disorders
Erythema multiforme	0/62 (0%)		1/57 (1.8%)
Erythroderma	0/62 (0%)		1/57 (1.8%)
Rash acneiform	0/62 (0%)		2/57 (3.5%)
Rash maculo-papular	0/62 (0%)		4/57 (7%)
Stevens-Johnson syndrome	0/62 (0%)		1/57 (1.8%)
Vascular disorders
Hypertension	0/62 (0%)		4/57 (7%)
Hypotension	0/62 (0%)		2/57 (3.5%)
Thromboembolic event	0/62 (0%)		3/57 (5.3%)
Visceral arterial ischemia	1/62 (1.6%)		0/57 (0%)
Other (Not Including Serious) Adverse Events
	mFOLFOX		MK2206 and Selumetinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	56/62 (90.3%)		53/57 (93%)
Blood and lymphatic system disorders
Anemia	26/62 (41.9%)		17/57 (29.8%)
Gastrointestinal disorders
Abdominal distension	0/62 (0%)		3/57 (5.3%)
Abdominal pain	26/62 (41.9%)		14/57 (24.6%)
Ascites	1/62 (1.6%)		3/57 (5.3%)
Bloating	5/62 (8.1%)		2/57 (3.5%)
Constipation	25/62 (40.3%)		8/57 (14%)
Diarrhea	23/62 (37.1%)		17/57 (29.8%)
Dry mouth	0/62 (0%)		7/57 (12.3%)
Dyspepsia	4/62 (6.5%)		4/57 (7%)
Flatulence	1/62 (1.6%)		4/57 (7%)
Mucositis oral	8/62 (12.9%)		12/57 (21.1%)
Nausea	39/62 (62.9%)		25/57 (43.9%)
Vomiting	21/62 (33.9%)		21/57 (36.8%)
General disorders
Chills	2/62 (3.2%)		10/57 (17.5%)
Edema face	0/62 (0%)		6/57 (10.5%)
Edema limbs	6/62 (9.7%)		9/57 (15.8%)
Fatigue	39/62 (62.9%)		25/57 (43.9%)
Fever	4/62 (6.5%)		6/57 (10.5%)
Pain	4/62 (6.5%)		0/57 (0%)
Infections and infestations
Infections and infestations-Other	1/62 (1.6%)		6/57 (10.5%)
Investigations
Alanine aminotransferase increased	9/62 (14.5%)		17/57 (29.8%)
Alkaline phosphatase increased	18/62 (29%)		13/57 (22.8%)
Aspartate aminotransferase increased	13/62 (21%)		20/57 (35.1%)
Blood bilirubin increased	5/62 (8.1%)		3/57 (5.3%)
Creatinine increased	3/62 (4.8%)		9/57 (15.8%)
Investigations-Other	4/62 (6.5%)		4/57 (7%)
Lymphocyte count decreased	15/62 (24.2%)		8/57 (14%)
Neutrophil count decreased	12/62 (19.4%)		1/57 (1.8%)
Platelet count decreased	21/62 (33.9%)		6/57 (10.5%)
Weight loss	13/62 (21%)		6/57 (10.5%)
White blood cell decreased	13/62 (21%)		1/57 (1.8%)
Metabolism and nutrition disorders
Anorexia	25/62 (40.3%)		20/57 (35.1%)
Dehydration	7/62 (11.3%)		6/57 (10.5%)
Hyperglycemia	20/62 (32.3%)		22/57 (38.6%)
Hypoalbuminemia	20/62 (32.3%)		17/57 (29.8%)
Hypocalcemia	9/62 (14.5%)		7/57 (12.3%)
Hypokalemia	11/62 (17.7%)		4/57 (7%)
Hypomagnesemia	5/62 (8.1%)		2/57 (3.5%)
Hyponatremia	10/62 (16.1%)		15/57 (26.3%)
Musculoskeletal and connective tissue disorders
Back pain	10/62 (16.1%)		3/57 (5.3%)
Generalized muscle weakness	4/62 (6.5%)		6/57 (10.5%)
Nervous system disorders
Dizziness	4/62 (6.5%)		10/57 (17.5%)
Dysgeusia	8/62 (12.9%)		8/57 (14%)
Headache	6/62 (9.7%)		2/57 (3.5%)
Paresthesia	7/62 (11.3%)		0/57 (0%)
Peripheral sensory neuropathy	29/62 (46.8%)		4/57 (7%)
Psychiatric disorders
Anxiety	5/62 (8.1%)		4/57 (7%)
Depression	4/62 (6.5%)		4/57 (7%)
Insomnia	8/62 (12.9%)		4/57 (7%)
Respiratory, thoracic and mediastinal disorders
Cough	11/62 (17.7%)		2/57 (3.5%)
Dyspnea	6/62 (9.7%)		7/57 (12.3%)
Pleural effusion	1/62 (1.6%)		3/57 (5.3%)
Skin and subcutaneous tissue disorders
Alopecia	12/62 (19.4%)		0/57 (0%)
Dry skin	6/62 (9.7%)		5/57 (8.8%)
Pruritus	2/62 (3.2%)		8/57 (14%)
Rash acneiform	0/62 (0%)		9/57 (15.8%)
Rash maculo-papular	3/62 (4.8%)		18/57 (31.6%)
Skin and subcutaneous tissue disorders - Other	1/62 (1.6%)		3/57 (5.3%)
Vascular disorders
Hypertension	8/62 (12.9%)		7/57 (12.3%)
Hypotension	3/62 (4.8%)		4/57 (7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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