Sorafenib and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00826540
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 83
• Locations: 211
• Arm: 1
• Actual Duration (Months): 53
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial is studying how well giving sorafenib together with bevacizumab works in treating patients with metastatic colorectal cancer. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Sorafenib and bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with bevacizumab may kill more tumor cells

Condition or Disease	Intervention/Treatment	Phase
Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage IV Colon Cancer; Stage IV Rectal Cancer	Drug: sorafenib tosylate; Biological: bevacizumab	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Evaluate proportion of patients who are progression-free at 3 months (in historic comparison with results for single-agent bevacizumab in ECOG 3200).

SECONDARY OBJECTIVES:

1. Response rate (RR) II. Overall survival (OS) III. Safety IV. Feasibility

OUTLINE: This is a multicenter study.

Patients receive sorafenib tosylate orally twice daily on days 1-5 and 8-12 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and then periodically during study treatment for laboratory biomarker and pharmacogenetic studies.

After completion of study treatment, patients are followed periodically for up to 2 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 83 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Sorafenib/Avastin® as Salvage Therapy in Patients With Metastatic Colorectal Cancer
• Actual Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (sorafenib tosylate and bevacizumab) Patients receive sorafenib tosylate orally twice daily on days 1-5 and 8-12 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and then periodically during study treatment for laboratory biomarker and pharmacogenetic studies

Drug: sorafenib tosylate; Given orally; Other Names: BAY 43-9006 BAY 43-9006 Tosylate Salt BAY 54-9085 Nexavar SFN ; Biological: bevacizumab; Given IV; Other Names: anti-VEGF humanized monoclonal antibody anti-VEGF monoclonal antibody Avastin rhuMAb VEGF

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival Rate [At 3 months]

   The primary endpoint of this trial is progression free survival at 3 months. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be considered evaluable. Patients lost to follow-up before 3 months (e.g., progression, refusing further treatment, etc.) will be considered treatment failures. All eligible patients will be followed until death or a minimum of 3 years. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Progression is defined as at least a 20% increase in the sum of longest liameter of target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

Secondary Outcome Measures

1. Response Rate [Up to 2 years]

   Simple frequency analysis will be conducted to see if response rate is related to prior treatment and the selected tumor biomarkers. Descriptive statistics will be used to investigate how prior treatment affects various other measures as well.

2. Overall Survival [Time from registration to death, assessed up to 2 years]

   The distribution of overall survival will be estimated using Kaplan-Meier methodology.

3. Feasibility of Study Treatment [Up to 2 years]

   Will be evaluated based on the number of patients who are able to> tolerate the regimen, how long they tolerate it and whether they elect to stop treatment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of stage IV colorectal cancer (histologic proof is not required)

• Measurable disease

• Spiral CT scan required for both pre- and post-treatment tumor assessments of lesions measuring 1-2 cm

• Progressive disease during or within 6 months of most recent prior chemotherapy regimen (bevacizumab, fluoropyrimidine, oxaliplatin, or irinotecan-based treatment) OR considered ineligible for standard therapy

• Documentation of submission of tumor material for Kirsten Rat Sarcoma (KRAS) testing available

• Prior anti-epidermal growth factor receptor (EGFR) antibody therapy (e.g., cetuximab or panitumumab) required for patients with wild-type KRAS tumor

• No known brain metastasis

• Patients with neurological symptoms must undergo a CT scan or MRI of the brain to exclude brain metastasis

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Life expectancy ≥ 6 months

• Hemoglobin ≥ 9.0 g/dL

• Absolute neutrophil count (ANC) ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• White blood cell count (WBC) ≥ 3,400/mm³

• International normalized ratio (INR) < 1.5 (≤ 3.0 if on anti-coagulation therapy [e.g., warfarin or heparin])

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

• Aspartate aminotransferase (AST) ≤ 2.5 times ULN (≤ 5 times ULN if there is liver involvement)

• Alkaline phosphatase ≤ 3 times ULN

• Creatinine ≤ 1.5 times ULN

• Urine protein:creatinine ratio < 1 OR urine dipstick < 2+ OR urine protein < 1,000 mg by 24-hour urine collection

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment (≥ 2 weeks after completion of treatment with sorafenib tosylate alone)

• Willing to provide mandatory blood samples for translational research studies

• Able to swallow whole pills

• No inadequately controlled hypertension (i.e., systolic BP > 150 mm Hg or diastolic BP

100 mm Hg on anti-hypertensive medications)

• No prior hypertensive crisis or hypertensive encephalopathy

• No myocardial infarction or unstable angina within the past 6 months

• No congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

• No thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months

• No hemorrhage or bleeding event > grade 3 within the past 4 weeks

• No evidence or history of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)

• No greater than normal risk of bleeding

• No active or recent hemoptysis (≥ ½ teaspoon of bright red blood per episode) within the past 30 days

• No concurrent uncontrolled illness including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia requiring anti-arrhythmic drugs

• Psychiatric illness or social situations that would limit compliance with study requirements

• No known HIV infection or chronic hepatitis B or C infection

• No serious, non-healing wound, active ulcer, or untreated bone fracture

• Patients with fractures secondary to metastatic disease are eligible after appropriate radiotherapy

• No significant traumatic injury within the past 4 weeks

• No known or suspected allergy or hypersensitivity to any component of bevacizumab, sorafenib tosylate, or their excipients or to any other agent given in the course of this study

• No malabsorption problem

• None of the following within the past 6 months:

• Significant vascular disease (e.g., aortic aneurysm or aortic dissection)

• Peripheral arterial thrombosis

• Symptomatic peripheral vascular disease

• Abdominal fistula

• Gastrointestinal perforation

• Intra-abdominal abscess

• No other active malignancy within the past 3 years except non melanoma skin cancer or carcinoma in situ of the cervix

• Prior malignancy allowed provided patient is not receiving other specific treatment for that malignancy (other than hormonal therapy)

• No other concurrent investigational agent for this cancer

• Prior radiotherapy allowed

• No prior sorafenib tosylate

• No prior discontinuation of bevacizumab due to adverse events

• More than 4 weeks since prior and no concurrent participation in any other experimental drug study

• More than 4 weeks since prior St. John's wort or rifampin

• More than 4 weeks since prior and no concurrent major surgical procedure or open biopsy

• More than 7 days since prior core biopsy or minor surgical procedure, including placement of a vascular access device

• No concurrent anticoagulant, except low-dose warfarin or heparin for deep venous thrombosis prophylaxis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
2	The Medical Center of Aurora	Aurora	Colorado	United States	80012
3	Boulder Community Hospital	Boulder	Colorado	United States	80301
4	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
5	Saint Anthony Central Hospital	Denver	Colorado	United States	80204
6	Porter Adventist Hospital	Denver	Colorado	United States	80210
7	Exempla Saint Joseph Hospital	Denver	Colorado	United States	80218
8	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
9	Rose Medical Center	Denver	Colorado	United States	80220
10	Colorado Cancer Research Program CCOP	Denver	Colorado	United States	80224-2522
11	Swedish Medical Center	Englewood	Colorado	United States	80110
12	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81502
13	North Colorado Medical Center	Greeley	Colorado	United States	80631
14	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
15	Longmont United Hospital	Longmont	Colorado	United States	80501
16	McKee Medical Center	Loveland	Colorado	United States	80539
17	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
18	North Suburban Medical Center	Thornton	Colorado	United States	80229
19	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
20	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
21	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
22	Graham Hospital Association	Canton	Illinois	United States	61520
23	Memorial Hospital	Carthage	Illinois	United States	62321
24	Eureka Hospital	Eureka	Illinois	United States	61530
25	Galesburg Clinic	Galesburg	Illinois	United States	61401
26	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
27	Mason District Hospital	Havana	Illinois	United States	62644
28	Mcdonough District Hospital	Macomb	Illinois	United States	61455
29	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois	United States	61265
30	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois	United States	61265
31	Sharis, Christine M MD (UIA Investigator)	Moline	Illinois	United States	61265
32	Stoffel, Thomas J MD (UIA Investigator)	Moline	Illinois	United States	61265
33	Holy Family Medical Center	Monmouth	Illinois	United States	61462
34	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
35	Community Cancer Center Foundation	Normal	Illinois	United States	61761
36	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
37	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
38	Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
39	Pekin Hospital	Pekin	Illinois	United States	61554
40	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61603
41	Proctor Hospital	Peoria	Illinois	United States	61614
42	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
43	Illinois Oncology Research Association CCOP	Peoria	Illinois	United States	61615
44	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
45	Illinois Valley Hospital	Peru	Illinois	United States	61354
46	Perry Memorial Hospital	Princeton	Illinois	United States	61356
47	Saint Margaret's Hospital	Spring Valley	Illinois	United States	61362
48	Saint Francis Hospital and Health Centers	Beech Grove	Indiana	United States	46107
49	Elkhart General Hospital	Elkhart	Indiana	United States	46515
50	Community Howard Regional Health	Kokomo	Indiana	United States	46904
51	Indiana University Health La Porte Hospital	La Porte	Indiana	United States	46350
52	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545-1470
53	Reid Hospital and Health Care Services	Richmond	Indiana	United States	47374
54	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
55	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46601
56	South Bend Clinic	South Bend	Indiana	United States	46617
57	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa	United States	52722
58	Cedar Rapids Oncology Association	Cedar Rapids	Iowa	United States	52403
59	Mercy Hospital	Cedar Rapids	Iowa	United States	52403
60	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
61	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
62	Mercy Capitol	Des Moines	Iowa	United States	50307
63	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
64	Iowa Oncology Research Association CCOP	Des Moines	Iowa	United States	50309
65	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
66	Medical Oncology and Hematology Associates	Des Moines	Iowa	United States	50314
67	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
68	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
69	Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
70	Siouxland Hematology Oncology Associates	Sioux City	Iowa	United States	51101
71	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51104
72	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
73	Hospital District Sixth of Harper County	Anthony	Kansas	United States	67003
74	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
75	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
76	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
77	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
78	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
79	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
80	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
81	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
82	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
83	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
84	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
85	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
86	Associates In Womens Health	Wichita	Kansas	United States	67208
87	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
88	Cancer Center of Kansas - Main Office	Wichita	Kansas	United States	67214
89	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
90	Wichita CCOP	Wichita	Kansas	United States	67214
91	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
92	Bixby Medical Center	Adrian	Michigan	United States	49221
93	Hickman Cancer Center	Adrian	Michigan	United States	49221
94	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
95	Michigan Cancer Research Consortium Community Clinical Oncology Program	Ann Arbor	Michigan	United States	48106
96	Oakwood Hospital	Dearborn	Michigan	United States	48124
97	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
98	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49431
99	Hurley Medical Center	Flint	Michigan	United States	48502
100	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
101	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan	United States	49801
102	Allegiance Health	Jackson	Michigan	United States	49201
103	Sparrow Hospital	Lansing	Michigan	United States	48912
104	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
105	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
106	Mercy Memorial Hospital	Monroe	Michigan	United States	48162
107	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
108	Saint Joseph Mercy Port Huron	Port Huron	Michigan	United States	48060
109	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
110	Lakeland Hospital	Saint Joseph	Michigan	United States	49085
111	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
112	Sanford Clinic North-Bemidgi	Bemidji	Minnesota	United States	56601
113	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
114	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
115	Essentia Health Duluth Clinic CCOP	Duluth	Minnesota	United States	55805
116	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
117	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
118	Fairview-Southdale Hospital	Edina	Minnesota	United States	55435
119	Unity Hospital	Fridley	Minnesota	United States	55432
120	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
121	Immanuel-Saint Joseph Hospital-Mayo Health System	Mankato	Minnesota	United States	56002
122	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
123	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
124	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
125	Virginia Piper Cancer Institute	Minneapolis	Minnesota	United States	55407
126	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
127	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
128	Mayo Clinic	Rochester	Minnesota	United States	55905
129	Metro-Minnesota CCOP	Saint Louis Park	Minnesota	United States	55416
130	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
131	Regions Hospital	Saint Paul	Minnesota	United States	55101
132	United Hospital	Saint Paul	Minnesota	United States	55102
133	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
134	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
135	Minnesota Oncology and Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
136	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
137	Center for Cancer Care and Research	Saint Louis	Missouri	United States	63141
138	Saint John's Hospital	Springfield	Missouri	United States	65804
139	Montana Cancer Consortium CCOP	Billings	Montana	United States	59101
140	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
141	Saint Vincent Healthcare	Billings	Montana	United States	59101
142	Hematology-Oncology Centers of the Northern Rockies PC	Billings	Montana	United States	59102
143	Billings Clinic	Billings	Montana	United States	59107-7000
144	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
145	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
146	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana	United States	59405
147	Great Falls Clinic	Great Falls	Montana	United States	59405
148	Northern Montana Hospital	Havre	Montana	United States	59501
149	Saint Peter's Community Hospital	Helena	Montana	United States	59601
150	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
151	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
152	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
153	Community Medical Hospital	Missoula	Montana	United States	59801
154	Montana Cancer Specialists	Missoula	Montana	United States	59802
155	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
156	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
157	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
158	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
159	Saint Alexius Medical Center	Bismarck	North Dakota	United States	58501
160	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
161	Sanford Clinic North-Fargo	Fargo	North Dakota	United States	58122
162	Sanford Medical Center-Fargo	Fargo	North Dakota	United States	58122
163	Altru Cancer Center	Grand Forks	North Dakota	United States	58201
164	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio	United States	43402
165	North Coast Cancer Care-Clyde	Clyde	Ohio	United States	43410
166	Grandview Hospital	Dayton	Ohio	United States	45405
167	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
168	Miami Valley Hospital	Dayton	Ohio	United States	45409
169	Samaritan North Health Center	Dayton	Ohio	United States	45415
170	Dayton CCOP	Dayton	Ohio	United States	45420
171	Hematology Oncology Center Incorporated	Elyria	Ohio	United States	44035
172	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
173	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
174	Wayne Hospital	Greenville	Ohio	United States	45331
175	Kettering Medical Center	Kettering	Ohio	United States	45429
176	Lima Memorial Hospital	Lima	Ohio	United States	45804
177	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio	United States	43537-1839
178	Saint Luke's Hospital	Maumee	Ohio	United States	43537
179	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio	United States	43537
180	Saint Charles Hospital	Oregon	Ohio	United States	43616
181	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio	United States	43616
182	North Coast Cancer Care	Sandusky	Ohio	United States	44870
183	Flower Hospital	Sylvania	Ohio	United States	43560
184	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
185	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio	United States	43606
186	Saint Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
187	University of Toledo	Toledo	Ohio	United States	43614
188	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio	United States	43617
189	Mercy Cancer Center at Saint Anne Mercy Hospital	Toledo	Ohio	United States	43623
190	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
191	Upper Valley Medical Center	Troy	Ohio	United States	45373
192	Fulton County Health Center	Wauseon	Ohio	United States	43567
193	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
194	Greene Memorial Hospital	Xenia	Ohio	United States	45385
195	Adventist Medical Center	Portland	Oregon	United States	97216
196	Geisinger Medical Center	Danville	Pennsylvania	United States	17822-2001
197	Geisinger Medical Center-Cancer Center Hazelton	Hazleton	Pennsylvania	United States	18201
198	Geisinger Medical Group	State College	Pennsylvania	United States	16801
199	Geisinger Wyoming Valley	Wilkes-Barre	Pennsylvania	United States	18711
200	Fredericksburg Oncology Inc	Fredericksburg	Virginia	United States	22401
201	Midelfort Clinic-Clairemont Campus	Eau Claire	Wisconsin	United States	54702
202	Mayo Clinic Health System Eau Claire Hospital - Luther Campus	Eau Claire	Wisconsin	United States	54703
203	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
204	Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
205	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
206	Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
207	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
208	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
209	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
210	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
211	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

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

Investigators

• Study Chair: Axel Grothey, MD, North Central Cancer Treatment Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00826540
• Other Study ID Numbers: NCCTG-N054C; NCI-2009-01177; U10CA025224; CDR0000632342
• First Posted: Jan 22, 2009
• Last Update Posted: Sep 6, 2017
• Last Verified: Aug 1, 2017

• Additional relevant MeSH terms: Rectal Neoplasms; Colonic Neoplasms; Recurrence; Bevacizumab; Antineoplastic Agents, Immunological; Sorafenib; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	83 patients were registered between 06/03/2009 and 10/20/2009 from 25 North Central Cancer Treatment Group (NCCTG) sites.
Pre-assignment Detail	One patient withdrew from the study and three patients were ineligible, therefore, these patients were excluded from all results.

Arm/Group Title	Treatment (Sorafenib Tosylate and Bevacizumab)
Arm/Group Description	Patients receive sorafenib tosylate orally twice daily on days 1-5 and 8-12 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and then periodically during study treatment for laboratory biomarker and pharmacogenetic studies> > sorafenib tosylate: Given orally> > bevacizumab: Given IV
Period Title: Overall Study
STARTED	83
COMPLETED	79
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Treatment (Sorafenib Tosylate and Bevacizumab)
Arm/Group Description	Patients receive sorafenib tosylate orally twice daily on days 1-5 and 8-12 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and then periodically during study treatment for laboratory biomarker and pharmacogenetic studies> > sorafenib tosylate: Given orally> > bevacizumab: Given IV
Overall Participants	79
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62
Sex: Female, Male (Count of Participants)
Female	36 45.6%
Male	43 54.4%
Performance Score (participants) [Number]
0 (Fully active)	44 55.7%
1 (Restricted in physically strenuous activity)	35 44.3%
Kirsten rat sarcoma (KRAS) (participants) [Number]
Wild-type	39 49.4%
Mutated	40 50.6%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival Rate
Description	The primary endpoint of this trial is progression free survival at 3 months. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be considered evaluable. Patients lost to follow-up before 3 months (e.g., progression, refusing further treatment, etc.) will be considered treatment failures. All eligible patients will be followed until death or a minimum of 3 years. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Progression is defined as at least a 20% increase in the sum of longest liameter of target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
Time Frame	At 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Sorafenib Tosylate and Bevacizumab)
Arm/Group Description	Patients receive sorafenib tosylate orally twice daily on days 1-5 and 8-12 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and then periodically during study treatment for laboratory biomarker and pharmacogenetic studies > > sorafenib tosylate: Given orally > > bevacizumab: Given IV
Measure Participants	79
Number (95% Confidence Interval) [percentage of participants]	53.2 67.3%

2. Secondary Outcome

Title	Response Rate
Description	Simple frequency analysis will be conducted to see if response rate is related to prior treatment and the selected tumor biomarkers. Descriptive statistics will be used to investigate how prior treatment affects various other measures as well.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Overall Survival
Description	The distribution of overall survival will be estimated using Kaplan-Meier methodology.
Time Frame	Time from registration to death, assessed up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Feasibility of Study Treatment
Description	Will be evaluated based on the number of patients who are able to> tolerate the regimen, how long they tolerate it and whether they elect to stop treatment.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Treatment (Sorafenib Tosylate and Bevacizumab)
Arm/Group Description	bevacizumab: Given IV
All Cause Mortality
	Treatment (Sorafenib Tosylate and Bevacizumab)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Sorafenib Tosylate and Bevacizumab)
	Affected / at Risk (%)	# Events
Total	13/79 (16.5%)
Blood and lymphatic system disorders
Hemoglobin decreased	1/79 (1.3%)	1
Gastrointestinal disorders
Abdominal pain	1/79 (1.3%)	1
Diarrhea	2/79 (2.5%)	2
Esophageal varices hemorrhage	1/79 (1.3%)	1
Ileus	1/79 (1.3%)	1
Nausea	1/79 (1.3%)	1
Rectal fistula	1/79 (1.3%)	1
Small intestinal obstruction	1/79 (1.3%)	1
Investigations
Alkaline phosphatase increased	1/79 (1.3%)	1
Amylase increased	1/79 (1.3%)	1
Bilirubin increased	1/79 (1.3%)	1
Cardiac troponin I increased	1/79 (1.3%)	1
Creatinine increased	2/79 (2.5%)	2
Lipase increased	2/79 (2.5%)	2
Weight loss	1/79 (1.3%)	1
Metabolism and nutrition disorders
Anorexia	1/79 (1.3%)	1
Dehydration	1/79 (1.3%)	1
Renal and urinary disorders
Renal failure	1/79 (1.3%)	1
Skin and subcutaneous tissue disorders
Rash desquamating	1/79 (1.3%)	1
Vascular disorders
Hypertension	3/79 (3.8%)	3
Thrombosis	1/79 (1.3%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Sorafenib Tosylate and Bevacizumab)
	Affected / at Risk (%)	# Events
Total	78/79 (98.7%)
Blood and lymphatic system disorders
Hemoglobin decreased	5/79 (6.3%)	9
Cardiac disorders
Left ventricular dysfunction	1/79 (1.3%)	1
Left ventricular failure	1/79 (1.3%)	1
Myocardial ischemia	1/79 (1.3%)	1
Gastrointestinal disorders
Abdominal distension	2/79 (2.5%)	3
Abdominal pain	37/79 (46.8%)	119
Ascites	1/79 (1.3%)	2
Colitis	1/79 (1.3%)	1
Colonic obstruction	1/79 (1.3%)	2
Colonic perforation	1/79 (1.3%)	1
Constipation	5/79 (6.3%)	6
Diarrhea	49/79 (62%)	172
Dyspepsia	1/79 (1.3%)	2
Dysphagia	1/79 (1.3%)	1
Ear, nose and throat examination abnormal	22/79 (27.8%)	56
Flatulence	2/79 (2.5%)	7
Mucositis oral	23/79 (29.1%)	53
Nausea	37/79 (46.8%)	100
Rectal hemorrhage	1/79 (1.3%)	1
Small intestinal necrosis	1/79 (1.3%)	1
Vomiting	19/79 (24.1%)	61
General disorders
Disease progression	1/79 (1.3%)	1
Edema limbs	2/79 (2.5%)	2
Fatigue	74/79 (93.7%)	355
Fever	3/79 (3.8%)	3
General symptom	1/79 (1.3%)	1
Pain	2/79 (2.5%)	6
Infections and infestations
Abdominal infection	3/79 (3.8%)	4
Urinary tract infection	3/79 (3.8%)	3
Injury, poisoning and procedural complications
Wound dehiscence	2/79 (2.5%)	2
Investigations
Alanine aminotransferase increased	3/79 (3.8%)	6
Alkaline phosphatase increased	10/79 (12.7%)	29
Amylase increased	4/79 (5.1%)	8
Aspartate aminotransferase increased	7/79 (8.9%)	22
Bilirubin increased	4/79 (5.1%)	11
Creatinine increased	2/79 (2.5%)	2
Gamma-glutamyltransferase increased	1/79 (1.3%)	2
Leukocyte count decreased	1/79 (1.3%)	6
Lipase increased	7/79 (8.9%)	19
Lymphocyte count decreased	5/79 (6.3%)	8
Neutrophil count decreased	2/79 (2.5%)	6
Platelet count decreased	3/79 (3.8%)	19
Weight loss	45/79 (57%)	193
Metabolism and nutrition disorders
Anorexia	58/79 (73.4%)	198
Blood glucose increased	6/79 (7.6%)	14
Dehydration	3/79 (3.8%)	4
Serum albumin decreased	7/79 (8.9%)	20
Serum calcium decreased	4/79 (5.1%)	12
Serum calcium increased	1/79 (1.3%)	2
Serum glucose decreased	1/79 (1.3%)	1
Serum phosphate decreased	3/79 (3.8%)	4
Serum potassium decreased	2/79 (2.5%)	2
Serum potassium increased	1/79 (1.3%)	1
Serum sodium decreased	4/79 (5.1%)	14
Serum sodium increased	1/79 (1.3%)	2
Musculoskeletal and connective tissue disorders
Back pain	7/79 (8.9%)	15
Bone pain	1/79 (1.3%)	1
Chest wall pain	3/79 (3.8%)	4
Joint pain	3/79 (3.8%)	3
Muscle weakness	3/79 (3.8%)	3
Myalgia	3/79 (3.8%)	5
Pain in extremity	2/79 (2.5%)	4
Nervous system disorders
Dizziness	1/79 (1.3%)	1
Headache	1/79 (1.3%)	1
Peripheral motor neuropathy	1/79 (1.3%)	4
Peripheral sensory neuropathy	4/79 (5.1%)	8
Taste alteration	2/79 (2.5%)	4
Renal and urinary disorders
Glomerular filtration rate decreased	1/79 (1.3%)	1
Protein urine positive	40/79 (50.6%)	132
Renal failure	2/79 (2.5%)	2
Ureteric obstruction	1/79 (1.3%)	1
Reproductive system and breast disorders
Pelvic pain	1/79 (1.3%)	1
Scrotal pain	1/79 (1.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/79 (1.3%)	2
Dyspnea	5/79 (6.3%)	6
Hemorrhage nasal	1/79 (1.3%)	1
Pharyngeal examination abnormal	5/79 (6.3%)	8
Pharyngeal mucositis	6/79 (7.6%)	10
Pharyngolaryngeal pain	1/79 (1.3%)	1
Pneumothorax	1/79 (1.3%)	1
Skin and subcutaneous tissue disorders
Dry skin	2/79 (2.5%)	3
Hand-and-foot syndrome	38/79 (48.1%)	169
Rash desquamating	24/79 (30.4%)	71
Skin disorder	1/79 (1.3%)	1
Vascular disorders
Hypertension	43/79 (54.4%)	146
Hypotension	2/79 (2.5%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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