Combination Chemotherapy Before or After Surgery in Treating Patients With Colorectal Cancer With Liver Metastases That Could Be Removed By Surgery

• Sponsor: NSABP Foundation Inc (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01189227
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 9
• Locations: 283
• Arms: 2
• Duration (Months): 16
• Patients Per Site: 0
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to kill tumor cells or stop them from growing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving combination chemotherapy after surgery may kill any remaining tumor cells. It is not yet known whether giving combination chemotherapy before and after surgery is more effective than giving combination chemotherapy after surgery.

PURPOSE: This randomized phase III trial is studying giving combination chemotherapy before and after surgery to see how well it works compared to giving combination chemotherapy after surgery in treating patients with colorectal cancer with liver metastases that could be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer; Metastatic Cancer	Procedure: Postoperative chemotherapy; Procedure: Perioperative chemotherapy	Phase 3

Detailed Description

OBJECTIVES:

Primary

• To evaluate the difference in recurrence-free survival (RFS) of patients with potentially resectable hepatic colorectal metastases receiving perioperative (preoperative plus postoperative) adjuvant chemotherapy vs only postoperative adjuvant chemotherapy following liver resection for colorectal metastases.

Secondary

• To compare the proportion of patients between study arms who are R0 or R1 resected, alive, and free of recurrence at 6 months.

• To compare RFS between study arms in the cohort of patients event-free at 6 months.

• To compare overall survival between study arms.

• To evaluate the difference in R0 and combined R0 + R1 resection rates in patients receiving neoadjuvant therapy and those undergoing initial surgical resection.

• To compare the postoperative morbidity profile between study arms.

• To evaluate the safety and toxicity profile of postoperative and perioperative administration of chemotherapy and bevacizumab.

Tertiary

• To evaluate the relationship of baseline circulating tumor cells (CTC) to RFS.

• To evaluate the relationship of baseline CTC to R0 resection.

• To evaluate the relationship of pre-resection CTC in the preoperative therapy group only with RFS and R0 resection.

OUTLINE: This is a multicenter study. Patients are stratified by number of liver metastases (1-3 vs 4+), chemotherapy regimen* (mFOLFOX6 vs FOLFIRI), and synchronous** primary colorectal cancer (yes vs no). Patients are randomized to 1 of 2 treatment arms.

NOTE: *Patients who have not received previous oxaliplatin receive mFOLFOX6 chemotherapy comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on day 1. Patients who have received previous oxaliplatin receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on day 1.

NOTE: **Synchronous is defined as the detection (by imaging) of suspicious liver metastases within 90 days before or after the date of histologic diagnosis of the primary colon or rectal cancer.

• Arm 1 (postoperative): Patients undergo hepatic resection. Beginning 31-56 days after surgery, patients receive mFOLFOX6 or FOLFIRI chemotherapy IV on day 1 over 3 hours. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats every 2 weeks for 12 courses.

• Arm 2 (perioperative): Patients receive mFOLFOX6 or FOLFIRI chemotherapy IV over 3 hours on day 1. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats for every 2 weeks for 6 courses. Patients then undergo hepatic resection. Beginning 31-56 days after surgery, patients receive an additional 6 courses of mFOLFOX6 or FOLFIRI chemotherapy.

Blood and tumor tissue samples may be collected periodically for correlative studies.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Study Evaluating the Role of Perioperative Chemotherapy in Patients With Potentially Resectable Hepatic Colorectal Metastases
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: Postoperative chemotherapy Patients undergo hepatic resection. Beginning 31-56 days after surgery, patients receive mFOLFOX6 or FOLFIRI chemotherapy IV on day 1 over 3 hours. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats every 2 weeks for 12 cycles.	Procedure: Postoperative chemotherapy; Patients undergo hepatic resection. Beginning 31-56 days after surgery, patients receive mFOLFOX6 or FOLFIRI chemotherapy IV on day 1 over 3 hours. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats every 2 weeks for 12 cycles.
Experimental: Arm 2: Perioperative chemotherapy Patients receive mFOLFOX6 or FOLFIRI chemotherapy IV over 3 hours on day 1. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats for every 2 weeks for 6 cycles. Patients then undergo hepatic resection. Beginning 31-56 days after surgery, patients receive an additional 6 cycles of mFOLFOX6 or FOLFIRI chemotherapy.	Procedure: Perioperative chemotherapy; Patients receive mFOLFOX6 or FOLFIRI chemotherapy IV over 3 hours on day 1. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats for every 2 weeks for 6 cycles. Patients then undergo hepatic resection. Beginning 31-56 days after surgery, patients receive an additional 6 cycles of mFOLFOX6 or FOLFIRI chemotherapy.

Outcome Measures

Primary Outcome Measures

1. Recurrence-free Survival (RFS) [From study entry until the date of recurrence or death or for a maximum of 5 years.]

   Time to recurrence or death

Secondary Outcome Measures

1. RFS of Patients Event-free [From study entry until the date of recurrence or for a maximum of 6 months.]

2. Overall Survival [From study entry until the time of death or for a maximum of 5 years.]

3. The Difference in R0 and Combined R0 + R1 Resection Rates Between the Two Arms. [Assessed at the time of surgery]

4. Frequencies of Selected Postoperative Surgical Complications and Other Adverse Events Within 30 Days of Surgery [Assessed within 30 days from the time of surgery]

5. Frequencies of Adverse Events as Assessed by the NCI CTCAE v4.0 [From study entry through 3 months after the last treatment dose.]

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal adenocarcinoma

• Hepatic metastasis (no histologic confirmation required) and no evidence of extrahepatic metastatic disease within the past 4 weeks by one of the following imaging studies*:

• PET/CT scan with contrast

• PET scan AND CT scan with contrast

• PET scan AND MRI with contrast

• PET/CT scan without contrast AND MRI with contrast NOTE: *If findings noted in imaging study reports are equivocal, the determination of whether or not the findings represent extrahepatic disease will be at the investigator's discretion.

• No history of or concurrent evidence of extrahepatic metastases

• Patients with regional nodes that are suspicious on imaging and are associated with the primary colorectal tumor are eligible provided the nodes will be resected with the primary tumor after randomization

• No radiographic evidence of metastases to portal lymph nodes (node > 1 cm in diameter) unless the node(s) are proven by biopsy to be negative

• No anal, small bowel, or appendiceal carcinoma

• No sarcoma, lymphoma, or carcinoid colorectal malignant diseases

• Within 4 weeks before randomization, the liver metastases must be determined by a hepatic surgeon to be resectable based on meeting both of the following criteria:

• A complete resection can be performed in a single operation

• There are ≥ 2 uninvolved contiguous segments of the liver

• Meets one of the following criteria:

• Primary tumor and regional nodes resected with clear surgical margins and no evidence of extrahepatic disease

• Unresected primary tumor with plans to resect the primary tumor before randomization

• Unresected primary tumor with plans to resect the primary tumor and the liver metastases in a single surgical procedure performed after randomization

• No unresected primary tumor in the colon or rectum with significant symptoms related to obstruction or that will require radiotherapy

PATIENT CHARACTERISTICS:

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

• Life expectancy ≥ 5 years (excluding the diagnosis of metastatic CRC)

• absolute neutrophil count (ANC) ≥ 1,200/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 10 g/dL

• Total bilirubin ≤ upper limit of normal (ULN)

• aspartate aminotransferase (AST) ≤ 5.0 times ULN

• Alkaline phosphatase ≤ 5.0 times ULN

• Serum creatinine ≤ ULN OR calculated creatinine clearance ≥ 30 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for ≥ 180 days after completion of study treatment

• Considered a potential candidate for a major hepatic surgical procedure

• No grade 3 or 4 anorexia, grade 3 nausea, or vomiting ≥ grade 2 (per CTCAE v4.0) related to metastatic disease

• No paresthesias, peripheral sensory neuropathy, or peripheral motor neuropathy ≥ grade 2 per Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0 (patients with grade 2 neuropathy who will receive FOLFIRI are eligible)

• No uncontrolled high BP defined as systolic BP ≥ 160 mm Hg OR diastolic BP ≥ 100 mm Hg, with or without antihypertensive medication (patients with initial BP elevations are eligible provided initiation or adjustment of BP medication lowers pressure to meet this criteria)

• Documented history of congestive heart failure requiring chronic medical therapy

• No active inflammatory bowel disease

• No active infection or chronic infection requiring chronic suppressive antibiotics

• No known bleeding diathesis or coagulopathy

• No symptomatic interstitial pneumonitis OR definitive evidence of interstitial pneumonitis described on CT scan, MRI, or chest x-ray in asymptomatic patients

• No other malignancies unless the patient is considered to be disease-free and has completed therapy for the malignancy ≥ 1 year ago

• Patients with carcinoma in situ of the cervix, CRC in situ, melanoma in situ, or basal cell or squamous cell carcinoma of the skin diagnosed and treated at any time before study treatment are eligible

• No known Gilbert syndrome

• Not known to be homozygous for the UGT1A1 allele (for patients who will receive FOLFIRI chemotherapy)

• No prior serious hypersensitivity reaction to any of the agents administered as part of study treatment (determination of "serious" is at the investigator's discretion)

• No other serious concurrent medical condition that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to participate in the study, or cause a delay in the initiation of therapy (surgery or chemotherapy) longer than 4 weeks following randomization

• No psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements

• No pre-existing chronic hepatic disease (e.g., chronic active hepatitis, cirrhosis) that, in the opinion of the investigator and hepatic surgeon, would limit the patient's ability to undergo hepatic metastasectomy

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No previous hepatic-directed therapy, including hepatic resection and/or ablation, hepatic arterial infusion therapy, or hepatic radiotherapy

• Patients who have only had an incision or excisional biopsy are eligible

• No previous chemotherapy or any other systemic therapy for metastatic colorectal cancer (CRC)

• No prior or concurrent portal vein embolization or other hepatic preconditioning techniques

• At least 30 days since prior investigational products

• No intent to use ablation to treat any hepatic lesion

• No concurrent therapeutic doses of coumadin or equivalent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaiser Permanente - Deer Valley	Antioch	California	United States	94531
2	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
3	Kaiser Permanente - Fremont	Fremont	California	United States	94538
4	Kaiser Permanente Medical Center - Hayward	Hayward	California	United States	94545
5	Kaiser Permanente Medical Center - Oakland	Oakland	California	United States	94611
6	St. Joseph Hospital Regional Cancer Center - Orange	Orange	California	United States	92868
7	Kaiser Permanente Medical Center - Redwood City	Redwood City	California	United States	94063
8	Kaiser Permanente Medical Center - Richmond	Richmond	California	United States	94801
9	Kaiser Permanente Medical Center - Roseville	Roseville	California	United States	95661
10	South Sacramento Kaiser-Permanente Medical Center	Sacramento	California	United States	95823
11	Kaiser Permanente Medical Center - Sacramento	Sacramento	California	United States	95825
12	Kaiser Permanente Medical Office -Vandever Medical Office	San Diego	California	United States	92120
13	Kaiser Permanente Medical Center - San Francisco Geary Campus	San Francisco	California	United States	94115
14	Kaiser Permanente Medical Center - Santa Teresa	San Jose	California	United States	95119
15	Kaiser Foundation Hospital - San Rafael	San Rafael	California	United States	94903
16	Kaiser Permanente Medical Center - Santa Clara Kiely Campus	Santa Clara	California	United States	95051
17	Kaiser Permanente Medical Center - Santa Rosa	Santa Rosa	California	United States	95403
18	Kaiser Permanente Medical Center - South San Francisco	South San Francisco	California	United States	94080
19	Kaiser Permanente Medical Facility - Stockton	Stockton	California	United States	95210
20	Kaiser Permanente Medical Center - Vacaville	Vacaville	California	United States	95688
21	Kaiser Permanente Medical Center - Vallejo	Vallejo	California	United States	94589
22	Kaiser Permanente Medical Center - Walnut Creek	Walnut Creek	California	United States	94596
23	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado	United States	80045
24	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut	United States	06105
25	Manchester Memorial Hospital	Manchester	Connecticut	United States	06040
26	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware	United States	19958
27	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
28	Washington Cancer Institute at Washington Hospital Center	Washington	District of Columbia	United States	20010
29	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida	United States	32207
30	Lakeland Regional Cancer Center at Lakeland Regional Medical Center	Lakeland	Florida	United States	33805
31	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida	United States	32803-1273
32	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia	United States	30033
33	Kaiser Permanente - Moanalua Medical Center and Clinic	Honolulu	Hawaii	United States	96819
34	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
35	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
36	Graham Hospital	Canton	Illinois	United States	61520
37	Memorial Hospital	Carthage	Illinois	United States	62321
38	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
39	Eureka Community Hospital	Eureka	Illinois	United States	61530
40	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
41	Mason District Hospital	Havana	Illinois	United States	62644
42	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois	United States	60521
43	McDonough District Hospital	Macomb	Illinois	United States	61455
44	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
45	Community Cancer Center	Normal	Illinois	United States	61761
46	Advocate Christ Medical Center	Oak Lawn	Illinois	United States	60453-2699
47	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
48	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
49	Proctor Hospital	Peoria	Illinois	United States	61614
50	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
51	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
52	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
53	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
54	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
55	Perry Memorial Hospital	Princeton	Illinois	United States	61356
56	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
57	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
58	Elkhart Clinic, LLC	Elkhart	Indiana	United States	46514-2098
59	Howard Community Hospital	Kokomo	Indiana	United States	46904
60	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
61	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
62	Michiana Hematology-Oncology, PC - South Bend	South Bend	Indiana	United States	46601
63	McFarland Clinic, PC	Ames	Iowa	United States	50010
64	Medical Oncology and Hematology Associates - West Des Moines	Clive	Iowa	United States	50325
65	Mercy Cancer Center - West Lakes	Clive	Iowa	United States	50325
66	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
67	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
68	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
69	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
70	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
71	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
72	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1002
73	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
74	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
75	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51102
76	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
77	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
78	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
79	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
80	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
81	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
82	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
83	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
84	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas	United States	67901
85	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
86	Menorah Medical Center	Overland Park	Kansas	United States	66209
87	Saint Luke's Hospital - South	Overland Park	Kansas	United States	66213
88	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
89	CCOP - Kansas City	Prairie Village	Kansas	United States	66208
90	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
91	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67401
92	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
93	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
94	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
95	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
96	CCOP - Wichita	Wichita	Kansas	United States	67214
97	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
98	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
99	Central Baptist Hospital	Lexington	Kentucky	United States	40503-9985
100	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky	United States	40536-0093
101	Ochsner Health Center - Bluebonnet	Baton Rouge	Louisiana	United States	70809
102	Ochsner Health Center - Covington	Covington	Louisiana	United States	70433
103	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
104	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
105	Harry and Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center	Baltimore	Maryland	United States	21237
106	Union Hospital of Cecil County	Elkton MD	Maryland	United States	21921
107	Peninsula Regional Medical Center	Salisbury	Maryland	United States	21801
108	Berkshire Hematology Oncology, PC	Pittsfield	Massachusetts	United States	01201
109	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan	United States	49221
110	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
111	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
112	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
113	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
114	Hurley Medical Center	Flint	Michigan	United States	48503
115	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
116	Foote Memorial Hospital	Jackson	Michigan	United States	49201
117	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
118	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
119	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
120	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan	United States	48910
121	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
122	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
123	Mercy Memorial Hospital - Monroe	Monroe	Michigan	United States	48162
124	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
125	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
126	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
127	Lakeside Cancer Specialists, PLLC	Saint Joseph	Michigan	United States	49085
128	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan	United States	48075
129	St. John Macomb Hospital	Warren	Michigan	United States	48093
130	St. Joseph's Medical Center	Brainerd	Minnesota	United States	56401
131	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
132	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
133	CCOP - Duluth	Duluth	Minnesota	United States	55805
134	St. Luke's Hospital Cancer Care Center	Duluth	Minnesota	United States	55805
135	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
136	Fergus Falls Medical Group, PA	Fergus Falls	Minnesota	United States	56537
137	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
138	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
139	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
140	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
141	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
142	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
143	Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
144	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
145	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
146	United Hospital	Saint Paul	Minnesota	United States	55102
147	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
148	Regions Hospital Cancer Care Center	St. Paul	Minnesota	United States	55101
149	Lakeview Hospital	Stillwater	Minnesota	United States	55082
150	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
151	Willmar Cancer Center at Rice Memorial Hospital	Willmar	Minnesota	United States	56201
152	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
153	Goldschmidt Cancer Center	Jefferson City	Missouri	United States	65109
154	Saint Luke's Cancer Institute at Saint Luke's Hospital	Kansas City	Missouri	United States	64111
155	St. Joseph Medical Center	Kansas City	Missouri	United States	64114
156	North Kansas City Hospital	Kansas City	Missouri	United States	64116
157	Parvin Radiation Oncology	Kansas City	Missouri	United States	64116
158	Heartland Hematology Oncology Associates, Incorporated	Kansas City	Missouri	United States	64118
159	Research Medical Center	Kansas City	Missouri	United States	64132
160	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri	United States	64086
161	Liberty Hospital	Liberty	Missouri	United States	64068
162	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
163	Saint Louis University Cancer Center	Saint Louis	Missouri	United States	63110
164	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri	United States	63110
165	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
166	Comprehensive Cancer Care, PC	Saint Louis	Missouri	United States	63141
167	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
168	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
169	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
170	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
171	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59102
172	Billings Clinic - Downtown	Billings	Montana	United States	59107-7000
173	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
174	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
175	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
176	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana	United States	59405
177	St. Peter's Hospital	Helena	Montana	United States	59601
178	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
179	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
180	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
181	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
182	Cancer Resource Center - Lincoln	Lincoln	Nebraska	United States	68510
183	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
184	Immanuel Medical Center	Omaha	Nebraska	United States	68122
185	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
186	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
187	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
188	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
189	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
190	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
191	Charles R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York	United States	12801
192	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10016
193	Nalitt Cancer Institute at Staten Island University Hospital	Staten Island	New York	United States	10305
194	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
195	Leo W. Jenkins Cancer Center at ECU Medical School	Greenville	North Carolina	United States	27834
196	Kinston Medical Specialists	Kinston	North Carolina	United States	28501
197	Iredell Memorial Hospital	Statesville	North Carolina	United States	28677
198	Forsyth Regional Cancer Center at Forsyth Medical Center	Winston-Salem	North Carolina	United States	27103
199	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
200	CCOP - MeritCare Hospital	Fargo	North Dakota	United States	58122
201	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
202	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
203	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
204	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
205	CCOP - Columbus	Columbus	Ohio	United States	43215
206	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
207	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
208	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
209	Grandview Hospital	Dayton	Ohio	United States	45405
210	Good Samaritan Hospital	Dayton	Ohio	United States	45406
211	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
212	CCOP - Dayton	Dayton	Ohio	United States	45420
213	Grady Memorial Hospital	Delaware	Ohio	United States	43015
214	Community Cancer Center	Elyria	Ohio	United States	44035
215	Hematology Oncology Center	Elyria	Ohio	United States	44035
216	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
217	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
218	Wayne Hospital	Greenville	Ohio	United States	45331
219	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
220	Fairfield Medical Center	Lancaster	Ohio	United States	43130
221	Lima Memorial Hospital	Lima	Ohio	United States	45804
222	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
223	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
224	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
225	Fisher-Titus Medical Center	Norwalk	Ohio	United States	44857
226	St. Charles Mercy Hospital	Oregon	Ohio	United States	43616
227	North Coast Cancer Care, Incorporated	Sandusky	Ohio	United States	44870
228	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
229	Flower Hospital Cancer Center	Sylvania	Ohio	United States	43560
230	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
231	Toledo Hospital	Toledo	Ohio	United States	43606
232	St. Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
233	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
234	CCOP - Toledo Community Hospital	Toledo	Ohio	United States	43617
235	St. Anne Mercy Hospital	Toledo	Ohio	United States	43623
236	Toledo Clinic, Incorporated - Main Clinic	Toledo	Ohio	United States	43623
237	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
238	Fulton County Health Center	Wauseon	Ohio	United States	43567
239	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
240	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
241	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
242	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma	United States	73104
243	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma	United States	74136
244	Butler Memorial Hospital	Butler	Pennsylvania	United States	16001
245	Riddle Memorial Hospital Cancer Center	Media	Pennsylvania	United States	19063
246	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
247	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
248	UPMC Cancer Centers	Pittsburgh	Pennsylvania	United States	15232
249	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania	United States	19612-6052
250	Associates in Hematology-Oncology, PC at Crozer Regional Cancer Center	Upland	Pennsylvania	United States	19013
251	Bon Secours St. Francis Health System	Greenville	South Carolina	United States	29601
252	CCOP - Greenville	Greenville	South Carolina	United States	29615
253	Self Regional Cancer Center at Self Regional Medical Center	Greenwood	South Carolina	United States	29646
254	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
255	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
256	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
257	Parkland Memorial Hospital	Dallas	Texas	United States	75235
258	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390
259	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79410-1894
260	Sandra L. Maxwell Cancer Center	Cedar City	Utah	United States	84720
261	Logan Regional Hospital	Logan	Utah	United States	84321
262	Val and Ann Browning Cancer Center at McKay-Dee Hospital Center	Ogden	Utah	United States	84403
263	Utah Valley Regional Medical Center - Provo	Provo	Utah	United States	84604
264	Dixie Regional Medical Center - East Campus	Saint George	Utah	United States	84770
265	LDS Hospital	Salt Lake City	Utah	United States	84143
266	Danville Regional Medical Center	Danville	Virginia	United States	24541
267	Fredericksburg Oncology, Incorporated	Fredericksburg	Virginia	United States	22401
268	Overlake Cancer Center at Overlake Hospital Medical Center	Bellevue	Washington	United States	98004
269	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
270	Group Health Central Hospital	Seattle	Washington	United States	98112
271	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington	United States	98122-4307
272	Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital	Parkersburg	West Virginia	United States	26102
273	Marshfield Clinic - Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
274	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin	United States	54701
275	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
276	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
277	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin	United States	54548
278	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
279	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin	United States	54868
280	Marshfield Clinic at Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
281	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
282	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
283	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• NSABP Foundation Inc
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Norman Wolmark, MD, NSABP Foundation Inc

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NSABP Foundation Inc
• ClinicalTrials.gov Identifier: NCT01189227
• Other Study ID Numbers: NSABP C-11; NSABP-C-11
• First Posted: Aug 26, 2010
• Last Update Posted: May 10, 2013
• Last Verified: May 1, 2013

• Keywords provided by NSABP Foundation Inc: stage IV colon cancer; adenocarcinoma of the colon; stage IV rectal cancer; adenocarcinoma of the rectum; liver metastases
• Additional relevant MeSH terms: Colorectal Neoplasms; Neoplasm Metastasis

Study Results

Participant Flow

Arm/Group Title	Arm 1: Postoperative Chemotherapy	Arm 2: Perioperative Chemotherapy
Arm/Group Description	Patients undergo hepatic resection. Beginning 31-56 days after surgery, patients receive mFOLFOX6 or FOLFIRI chemotherapy IV on day 1 over 3 hours. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats every 2 weeks for 12 cycles.	Patients receive mFOLFOX6 or FOLFIRI chemotherapy IV over 3 hours on day 1. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats for every 2 weeks for 6 cycles. Patients then undergo hepatic resection. Beginning 31-56 days after surgery, patients receive an additional 6 cycles of mFOLFOX6 or FOLFIRI chemotherapy.
Period Title: Overall Study
STARTED	6	3
COMPLETED	0	0
NOT COMPLETED	6	3

Baseline Characteristics

Arm/Group Title	Postoperative Chemotherapy	Perioperative Chemotherapy	Total
Arm/Group Description	Postoperative chemotherapy	Perioperative chemotherapy	Total of all reporting groups
Overall Participants	6	3	9
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64 (14.9)	55 (13.9)	61 (14.4)
Sex: Female, Male (Count of Participants)
Female	5 83.3%	0 0%	5 55.6%
Male	1 16.7%	3 100%	4 44.4%

Outcome Measures

1. Primary Outcome

Title	Recurrence-free Survival (RFS)
Description	Time to recurrence or death
Time Frame	From study entry until the date of recurrence or death or for a maximum of 5 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: Postoperative Chemotherapy	Arm 2: Perioperative Chemotherapy
Arm/Group Description	Patients undergo hepatic resection. Beginning 31-56 days after surgery, patients receive mFOLFOX6 or FOLFIRI chemotherapy IV on day 1 over 3 hours. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats every 2 weeks for 12 cycles.	Patients receive mFOLFOX6 or FOLFIRI chemotherapy IV over 3 hours on day 1. Patients receive an additional dose of fluorouracil over 46 hours using a portable pump. Treatment repeats for every 2 weeks for 6 cycles. Patients then undergo hepatic resection. Beginning 31-56 days after surgery, patients receive an additional 6 cycles of mFOLFOX6 or FOLFIRI chemotherapy.
Measure Participants	0	0

2. Secondary Outcome

Title	RFS of Patients Event-free
Time Frame	From study entry until the date of recurrence or for a maximum of 6 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Overall Survival
Time Frame	From study entry until the time of death or for a maximum of 5 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	The Difference in R0 and Combined R0 + R1 Resection Rates Between the Two Arms.
Time Frame	Assessed at the time of surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Frequencies of Selected Postoperative Surgical Complications and Other Adverse Events Within 30 Days of Surgery
Time Frame	Assessed within 30 days from the time of surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Frequencies of Adverse Events as Assessed by the NCI CTCAE v4.0
Time Frame	From study entry through 3 months after the last treatment dose.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Adverse Event Reporting Description	Participants at Risk includes any patient who submitted an AE form.
Arm/Group Title	Postoperative Chemotherapy		Perioperative Chemotherapy
Arm/Group Description	Postoperative chemotherapy		Perioperative chemotherapy
All Cause Mortality
	Postoperative Chemotherapy		Perioperative Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Postoperative Chemotherapy		Perioperative Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/5 (20%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Postoperative Chemotherapy		Perioperative Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/5 (60%)		1/2 (50%)
Blood and lymphatic system disorders
Anemia	1/5 (20%)		0/2 (0%)
Gastrointestinal disorders
Abdominal pain	0/5 (0%)		1/2 (50%)
Diarrhea	1/5 (20%)		0/2 (0%)
Mucositis oral	1/5 (20%)		0/2 (0%)
Nausea	1/5 (20%)		0/2 (0%)
General disorders
Fatigue	1/5 (20%)		0/2 (0%)
Investigations
Alkaline phosphatase increased	1/5 (20%)		0/2 (0%)
Neutrophil count decreased	1/5 (20%)		0/2 (0%)
Metabolism and nutrition disorders
Anorexia	1/5 (20%)		0/2 (0%)
Dehydration	1/5 (20%)		0/2 (0%)
Hypokalemia	1/5 (20%)		0/2 (0%)
Nervous system disorders
Paresthesia	1/5 (20%)		0/2 (0%)
Peripheral motor neuropathy	1/5 (20%)		0/2 (0%)
Peripheral sensory neuropathy	1/5 (20%)		0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/5 (20%)		0/2 (0%)
Hypoxia	1/5 (20%)		0/2 (0%)

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.