Testing the Use of the Usual Chemotherapy Before and After Surgery for Removable Pancreatic Cancer

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Recruiting

CT.gov ID

NCT04340141

Collaborator

National Cancer Institute (NCI) (NIH)

352

Enrollment

183

Locations

Arms

124

Anticipated Duration (Months)

1.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase III trial compares perioperative chemotherapy (given before and after surgery) versus adjuvant chemotherapy (given after surgery) for the treatment of pancreatic cancer that can be removed by surgery (removable/resectable). Chemotherapy drugs, such as fluorouracil, irinotecan, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before and after surgery (perioperatively) may work better in treating patients with pancreatic cancer compared to giving chemotherapy after surgery (adjuvantly).

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Adenosquamous Carcinoma Resectable Pancreatic Adenocarcinoma Pancreatic Cancer	Drug: Oxaliplatin Drug: Irinotecan Hydrochloride Drug: Leucovorin Calcium Drug: Fluorouracil Procedure: Resection Other: Questionnaire Administration	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

To evaluate and compare overall survival (OS) in patients with resectable pancreatic adenocarcinoma treated with perioperative fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin (modified [m]FOLFIRINOX) and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX.

SECONDARY OBJECTIVES:

To evaluate and compare disease-free survival (DFS) in patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX.
To evaluate and compare time to locoregional recurrence (TLR) in patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX.
To evaluate and compare time to distant metastases (TDM) in patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX.
To evaluate and compare the R0 resection rate in patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX.
To evaluate and compare rate of unresectability in patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX.
To evaluate rate of pathologic complete response in patients randomized to the perioperative therapy arm.
To evaluate and compare mFOLFIRINOX dose intensity delivered and number of cycles received in patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX.
To evaluate and compare adverse event profile in patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX.
To compare physical functioning, nausea/vomiting, and diarrhea, as measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) between patients with resectable pancreatic adenocarcinoma treated with perioperative mFOLFIRINOX and surgery versus up-front surgery followed by adjuvant mFOLFIRINOX.
To prospectively assess the influence of diet, body mass index, weight loss, physical activity, and other lifestyle habits on the disease-free survival and overall survival among patients with localized pancreatic cancers.
To assess the influence of diet, obesity, physical activity, and other lifestyle habits on the risk of toxicity associated with chemotherapy.
To evaluate the ability of computed tomography (CT)-based radiomics in distinguishing post-neoadjuvant chemotherapy (NAC) fibrosis from viable tumor in patients randomized to the perioperative therapy arm.
To determine whether CT-based radiomics retrieved from baseline examination may act as non-invasive predictors of survival outcome in patients randomized to the adjuvant therapy arm.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Within 2-8 weeks of completing neoadjuvant chemotherapy, patients undergo surgical resection. Patients then receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo surgical resection. Beginning 3-12 weeks after surgery, patients then receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 6 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

352 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase III Trial of Perioperative Versus Adjuvant Chemotherapy for Resectable Pancreatic Cancer

Actual Study Start Date :

Jul 1, 2020

Anticipated Primary Completion Date :

Jan 1, 2026

Anticipated Study Completion Date :

Nov 1, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (perioperative chemotherapy, surgery) Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Within 2-8 weeks of completing neoadjuvant chemotherapy, patients undergo surgical resection. Patients then receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity.	Drug: Oxaliplatin Given IV Drug: Irinotecan Hydrochloride Given IV Drug: Leucovorin Calcium Given IV Drug: Fluorouracil Given IV Procedure: Resection Undergo surgical resection Other: Questionnaire Administration Ancillary studies
Active Comparator: Arm II (surgery, adjuvant chemotherapy) Patients undergo surgical resection. Beginning 3-12 weeks after surgery, patients then receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for 12 cycles in the absence of disease progression or unacceptable toxicity.	Drug: Oxaliplatin Given IV Drug: Irinotecan Hydrochloride Given IV Drug: Leucovorin Calcium Given IV Drug: Fluorouracil Given IV Procedure: Resection Undergo surgical resection Other: Questionnaire Administration Ancillary studies

Arm

Intervention/Treatment

Experimental: Arm I (perioperative chemotherapy, surgery)

Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Within 2-8 weeks of completing neoadjuvant chemotherapy, patients undergo surgical resection. Patients then receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Oxaliplatin

Given IV

Drug: Irinotecan Hydrochloride

Given IV

Drug: Leucovorin Calcium

Given IV

Drug: Fluorouracil

Given IV

Procedure: Resection

Undergo surgical resection

Other: Questionnaire Administration

Ancillary studies

Active Comparator: Arm II (surgery, adjuvant chemotherapy)

Patients undergo surgical resection. Beginning 3-12 weeks after surgery, patients then receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Oxaliplatin

Given IV

Drug: Irinotecan Hydrochloride

Given IV

Drug: Leucovorin Calcium

Given IV

Drug: Fluorouracil

Given IV

Procedure: Resection

Undergo surgical resection

Other: Questionnaire Administration

Ancillary studies

Outcome Measures

Primary Outcome Measures

Overall survival (OS) [Time between randomization and death from any cause, assessed up to 6 years.]
Overall survival is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. The treatment arms will be compared using a stratified Cox regression model, and hazard ratios from each arm will be estimated.

Secondary Outcome Measures

Disease-free survival (DFS) [Time between randomization and progression prior to surgery, metastases detected during surgery, recurrence (locoregional and/or distant) after resection, and death due to all causes, assessed up to 6 years.]
Disease-free survival (DFS) is defined as the time from randomization to the date of progression prior to surgery, metastases detected during surgery, recurrence (locoregional and/or distant) after resection, and death due to all causes, whichever occurs first. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time to locoregional recurrence (TLR) [Time between randomization and locoregional recurrence after resection, assessed up to 6 years.]
Time to locoregional recurrence (TLR) is defined as the time from randomization to the date of locoregional recurrence after resection. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time to distant metastases (TDM) [Time between randomization and metastases prior to surgery, metastases detected during surgery, or distant recurrence after resection, assessed up to 6 years.]
Time to distant metastases (TDM) is defined as the time from randomization to the date of metastases prior to surgery, metastases detected during surgery, or distant recurrence after resection. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
R0 resection rate [At time of surgery.]
The rate (percentage) of patients with negative resection margins after undergoing surgery.
Rate of unresectability [At time of surgery or planned time of surgery.]
The rate (percentage) of patients who cannot undergo surgery due to adverse events, progressive disease, death, poor performance, or patient/physician decision, are deemed unresectable before surgery, or resection was not performed during surgery.
Pathologic complete response (pCR) rate [At time of surgery.]
The rate (percentage) of patients who achieve a pathologic complete response (pCR) confirmed by histopathologic review of the surgical specimen.
Incidence of adverse events (AEs), assessed using National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) version 5.0 (v5.0) [Up to 2 years.]
The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns within treatment arms and during the following three time points: during perioperative chemotherapy, surgical complications during surgery and post-operative period for 30 days, and during adjuvant chemotherapy.
Fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin (modified [m]FOLFIRINOX) dose intensity delivered [8 months]
Dose intensity is defined as the percentage of total cumulative dose the patient received divided by the total dose planned per protocol times 100.
Fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin (modified [m]FOLFIRINOX) number of cycles received [8 months]
The number of cycles received is defined as the total number of cycles that the participant received at least one dose of any agent in mFOLFIRINOX.
Quality of life as assessed by the physical functioning, nausea/vomiting, and diarrhea subscales in the Quality of Life Questionnaire-Core 30 (QLQ-C30) [8 weeks]
Quality of Life Questionnaire-Core 30 (QLQ-C30) is a 30-item questionnaire to assess the overall quality of life in cancer patients. QLQ-C30 includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale; higher score=better level of physical functioning, greater occurrence of nausea/vomiting, and greater occurrence of diarrhea.
Influence of diet, body mass index, weight loss, physical activity, and other lifestyle habits on overall survival [Time between randomization and death from any cause, assessed up to 6 years.]
Multivariate Cox proportional hazards models will be fit for overall survival (OS) endpoint (defined above) with covariates corresponding to baseline diet and lifestyle questionnaire responses and hazard ratios and 95% confidence intervals will be reported.
Influence of diet, body mass index, weight loss, physical activity, and other lifestyle habits on disease-free survival (DFS) [Time between randomization and progression prior to surgery, metastases detected during surgery, recurrence (locoregional and/or distant) after resection, and death due to all causes, assessed up to 6 years.]
Multivariate Cox proportional hazards models will be fit for disease-free survival (DFS) endpoint (defined above) with covariates corresponding to baseline diet and lifestyle questionnaire responses and hazard ratios and 95% confidence intervals will be reported.
Influence of diet, body mass index, weight loss, physical activity, and other lifestyle habits on the risk of grade 3+ adverse event associated with chemotherapy [Up to 2 years.]
Multivariate Logistic models will be fit for the binary endpoint of grade 3+ adverse event (patient experiences at least one grade 3 or higher adverse event during treatment)
The ability of computed tomography (CT)-based radiomics to distinguish post-neoadjuvant chemotherapy (NAC) fibrosis from viable tumor as measured by comparison to histological evaluation [At time of surgery.]
Comparison between computed tomography (CT)-based radiomics and histological tumor fibrosis proportions will be measured using Spearman's rank correlation coefficient.
Computed tomography (CT)-based radiomics as non-invasive predictors of overall survival [Time between randomization and death from any cause, assessed up to 6 years.]
Multivariate Cox proportional hazards model will be fit for overall survival (OS) endpoint (defined above) with covariates chosen from all available radiomics features using the least absolute shrinkage and selection operator (LASSO) method with 10-fold cross-validation (CV) and additionally adjusted for clinically important confounders. After the final model is selected the area under the receiver operating characteristic curve (AUC) will be reported to indicate the prediction performance of the radiomics model.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

PRE-REGISTRATION:

Pathology: Histologic or cytologic proof of pancreatic adenocarcinoma or adenosquamous carcinoma
TNM Stage: Tx-4, N0-1, M0 (M0 disease does not include spread to distant lymph nodes and organs)
Resectable Primary Tumor: Local radiographic reading must be consistent with resectable disease defined as the following on 1) arterial and venous phase contrast-enhanced abdominal/pelvic CT scan or abdominal/pelvic magnetic resonance imaging (MRI) scan and 2) chest CT:
No involvement or abutment of the celiac artery, common hepatic artery, superior mesenteric artery, or replaced right hepatic artery (if applicable)
Less than 180 degree interface between tumor and vessel wall of the portal vein or superior mesenteric vein, and patent portal vein/splenic vein confluence
No evidence of metastatic disease
Measurable disease or non-measurable disease o Non-measurable disease is defined as cytologic or histologic confirmation of adenocarcinoma of adenosquamous carcinoma by fine needle aspiration or core-biopsy of the pancreas without measurable disease by radiographic imaging

REGISTRATION:

Confirmation of resectable disease by real-time central imaging review by the Alliance Imaging Core Lab at Imaging and Radiation Oncology Core (IROC) Ohio
Determined to be appropriate candidate for curative-intent pancreatectomy by surgeon intending to perform the resection
No prior radiation therapy, chemotherapy, targeted therapy, investigational therapy, or surgery for pancreatic cancer
Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects.
Therefore, for women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Total Neuropathy Score < 2
Absolute neutrophil count (ANC) >= 1,500/uL
Platelet count >= 100,000/uL
Total bilirubin =< 1.5 x upper limit of normal (ULN) (If obstructive jaundice is present, then biliary drainage must be initiated and total bilirubin =< 3.0)
Creatinine =< 1.5 x ULN OR calculated (Calc.) creatinine clearance >= 30 mL/min (Calculated using the Cockcroft-Gault equation)
No known Gilbert's Syndrome or known homozygosity for UGAT1A1*28 polymorphism
No comorbid conditions that would prohibit curative-intent pancreatectomy
Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug prior to registration
Chronic concomitant treatment with strong inducers of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inducers must discontinue the drug prior to registration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama	United States	36688
2	Anchorage Associates in Radiation Medicine	Anchorage	Alaska	United States	98508
3	Alaska Breast Care and Surgery LLC	Anchorage	Alaska	United States	99508
4	Alaska Oncology and Hematology LLC	Anchorage	Alaska	United States	99508
5	Alaska Women's Cancer Care	Anchorage	Alaska	United States	99508
6	Anchorage Oncology Centre	Anchorage	Alaska	United States	99508
7	Katmai Oncology Group	Anchorage	Alaska	United States	99508
8	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
9	Mercy Hospital Fort Smith	Fort Smith	Arkansas	United States	72903
10	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California	United States	95603
11	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
12	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
13	Mills-Peninsula Medical Center	Burlingame	California	United States	94010
14	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California	United States	95682
15	Memorial Medical Center	Modesto	California	United States	95355
16	Palo Alto Medical Foundation-Camino Division	Mountain View	California	United States	94040
17	Palo Alto Medical Foundation Health Care	Palo Alto	California	United States	94301
18	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California	United States	95661
19	Sutter Roseville Medical Center	Roseville	California	United States	95661
20	Sutter Medical Center Sacramento	Sacramento	California	United States	95816
21	California Pacific Medical Center-Pacific Campus	San Francisco	California	United States	94115
22	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California	United States	94086
23	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California	United States	95687
24	Sutter Solano Medical Center/Cancer Center	Vallejo	California	United States	94589
25	Danbury Hospital	Danbury	Connecticut	United States	06810
26	Norwalk Hospital	Norwalk	Connecticut	United States	06856
27	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
28	AdventHealth Altamonte	Altamonte Springs	Florida	United States	32701
29	Mount Sinai Comprehensive Cancer Center at Aventura	Aventura	Florida	United States	33180
30	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
31	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
32	AdventHealth Orlando	Orlando	Florida	United States	32803
33	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
34	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
35	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho	United States	83605
36	Kootenai Medical Center	Coeur d'Alene	Idaho	United States	83814
37	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho	United States	83619
38	Idaho Urologic Institute-Meridian	Meridian	Idaho	United States	83642
39	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho	United States	83642
40	Saint Alphonsus Medical Center-Nampa	Nampa	Idaho	United States	83686
41	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho	United States	83686
42	Kootenai Cancer Center	Post Falls	Idaho	United States	83854
43	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho	United States	83301
44	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
45	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
46	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
47	Memorial Hospital of Carbondale	Carbondale	Illinois	United States	62902
48	SIH Cancer Institute	Carterville	Illinois	United States	62918
49	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
50	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
51	University of Illinois	Chicago	Illinois	United States	60612
52	Carle on Vermilion	Danville	Illinois	United States	61832
53	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois	United States	62526
54	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
55	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois	United States	60115
56	Carle Physician Group-Effingham	Effingham	Illinois	United States	62401
57	Crossroads Cancer Center	Effingham	Illinois	United States	62401
58	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
59	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
60	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
61	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois	United States	60134
62	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
63	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
64	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois	United States	61938
65	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
66	Cancer Care Center of O'Fallon	O'Fallon	Illinois	United States	62269
67	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
68	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
69	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
70	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
71	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
72	Valley Radiation Oncology	Peru	Illinois	United States	61354
73	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
74	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
75	Springfield Clinic	Springfield	Illinois	United States	62702
76	Memorial Medical Center	Springfield	Illinois	United States	62781
77	Carle Cancer Center	Urbana	Illinois	United States	61801
78	The Carle Foundation Hospital	Urbana	Illinois	United States	61801
79	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois	United States	60555
80	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
81	Mary Greeley Medical Center	Ames	Iowa	United States	50010
82	McFarland Clinic PC - Ames	Ames	Iowa	United States	50010
83	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
84	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
85	Broadlawns Medical Center	Des Moines	Iowa	United States	50314
86	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
87	Methodist West Hospital	West Des Moines	Iowa	United States	50266-7700
88	Baptist Health Lexington	Lexington	Kentucky	United States	40503
89	Baptist Health Louisville	Louisville	Kentucky	United States	40207
90	Baptist Health Madisonville/Merle Mahr Cancer Center	Madisonville	Kentucky	United States	42431
91	Hickman Cancer Center	Adrian	Michigan	United States	49221
92	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
93	Saint Joseph Mercy Brighton	Brighton	Michigan	United States	48114
94	Saint Joseph Mercy Canton	Canton	Michigan	United States	48188
95	Saint Joseph Mercy Chelsea	Chelsea	Michigan	United States	48118
96	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
97	Weisberg Cancer Treatment Center	Farmington Hills	Michigan	United States	48334
98	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri	United States	63011
99	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
100	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
101	University of Missouri - Ellis Fischel	Columbia	Missouri	United States	65212
102	Capital Region Southwest Campus	Jefferson City	Missouri	United States	65109
103	Mercy Hospital Joplin	Joplin	Missouri	United States	64804
104	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
105	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
106	Heartland Regional Medical Center	Saint Joseph	Missouri	United States	64506
107	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
108	Mercy Hospital South	Saint Louis	Missouri	United States	63128
109	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
110	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
111	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri	United States	63670
112	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
113	CoxHealth South Hospital	Springfield	Missouri	United States	65807
114	Missouri Baptist Sullivan Hospital	Sullivan	Missouri	United States	63080
115	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri	United States	63127
116	Billings Clinic Cancer Center	Billings	Montana	United States	59101
117	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
118	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
119	Great Falls Clinic	Great Falls	Montana	United States	59405
120	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
121	Community Medical Hospital	Missoula	Montana	United States	59804
122	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
123	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
124	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
125	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
126	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
127	Hematology Oncology Associates of Central New York-East Syracuse	East Syracuse	New York	United States	13057
128	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
129	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
130	University of Rochester	Rochester	New York	United States	14642
131	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
132	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553
133	Sanford Broadway Medical Center	Fargo	North Dakota	United States	58122
134	Sanford Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
135	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
136	Mount Carmel East Hospital	Columbus	Ohio	United States	43213
137	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
138	Grant Medical Center	Columbus	Ohio	United States	43215
139	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
140	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
141	Doctors Hospital	Columbus	Ohio	United States	43228
142	Dublin Methodist Hospital	Dublin	Ohio	United States	43016
143	Mount Carmel Grove City Hospital	Grove City	Ohio	United States	43123
144	OhioHealth Mansfield Hospital	Mansfield	Ohio	United States	44903
145	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
146	Licking Memorial Hospital	Newark	Ohio	United States	43055
147	Newark Radiation Oncology	Newark	Ohio	United States	43055
148	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
149	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
150	Saint Ann's Hospital	Westerville	Ohio	United States	43081
151	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
152	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma	United States	73120
153	Saint Charles Health System	Bend	Oregon	United States	97701
154	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
155	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon	United States	97015
156	Bay Area Hospital	Coos Bay	Oregon	United States	97420
157	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
158	Providence Portland Medical Center	Portland	Oregon	United States	97213
159	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
160	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
161	Prisma Health Cancer Institute - Faris	Greenville	South Carolina	United States	29605
162	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
163	Prisma Health Cancer Institute - Greer	Greer	South Carolina	United States	29650
164	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina	United States	29672
165	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
166	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington	United States	98520
167	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
168	Providence Regional Cancer System-Centralia	Centralia	Washington	United States	98531
169	Swedish Cancer Institute-Edmonds	Edmonds	Washington	United States	98026
170	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
171	Swedish Cancer Institute-Issaquah	Issaquah	Washington	United States	98029
172	Providence Regional Cancer System-Lacey	Lacey	Washington	United States	98503
173	PeaceHealth Saint John Medical Center	Longview	Washington	United States	98632
174	Swedish Medical Center-Ballard Campus	Seattle	Washington	United States	98107
175	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
176	PeaceHealth United General Medical Center	Sedro-Woolley	Washington	United States	98284
177	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
178	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington	United States	99362
179	Langlade Hospital and Cancer Center	Antigo	Wisconsin	United States	54409
180	Aspirus Medford Hospital	Medford	Wisconsin	United States	54451
181	Aspirus Regional Cancer Center	Wausau	Wisconsin	United States	54401
182	Aspirus UW Cancer Center	Wisconsin Rapids	Wisconsin	United States	54494
183	Welch Cancer Center	Sheridan	Wyoming	United States	82801