Comparing Two Treatment Combinations, Gemcitabine and Nab-Paclitaxel With 5-Fluorouracil, Leucovorin, and Liposomal Irinotecan for Older Patients With Pancreatic Cancer That Has Spread

Sponsor

ECOG-ACRIN Cancer Research Group (Other)

Overall Status

Recruiting

CT.gov ID

NCT04233866

Collaborator

National Cancer Institute (NCI) (NIH)

184

Enrollment

Locations

Arms

42.4

Anticipated Duration (Months)

4.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II trial compares two treatment combinations: gemcitabine hydrochloride and nab-paclitaxel, or fluorouracil, leucovorin calcium, and liposomal irinotecan in older patients with pancreatic cancer that has spread to other places in the body (metastatic). Drugs used in chemotherapy, such as gemcitabine hydrochloride, nab-paclitaxel, fluorouracil, leucovorin calcium, and liposomal irinotecan, 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. This study may help doctors find out which treatment combination is better at prolonging life in older patients with metastatic pancreatic cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Pancreatic Adenocarcinoma Stage IV Pancreatic Cancer AJCC v8	Drug: Fluorouracil Drug: Gemcitabine Drug: Gemcitabine Hydrochloride Drug: Leucovorin Drug: Leucovorin Calcium Drug: Liposomal Irinotecan Drug: Nab-paclitaxel Other: Quality-of-Life Assessment Other: Questionnaire Administration	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

Overall survival.

SECONDARY OBJECTIVES:

Progression-free survival. II. Objective tumor response.

III. Comprehensive Geriatric Assessment (CGA)/quality of life (QOL) related objectives:

IIIa. Hypothesize that lower scores in functional status assessment tool - instrumental activities of daily living (IADL) will correlate with higher rates of grade 3 or higher chemotherapy toxicity.

IV. CGA/QOL related exploratory objectives:

IVa. Evaluation of other pre-treatment CGA domains including co-morbidities, depression, nutrition and cognition as predictors of chemotherapy tolerance.

IVb. Evaluation of the association between change in functional status during treatment course (comparison between activities of daily living [ADL] and IADL score pre-treatment and at time of disease evaluation) as predictors of chemotherapy tolerance.

IVc. Evaluation of the correlation between CGA domains and overall survival by treatment arm.

IVd. Evaluation of the difference in QOL scores (Functional Assessment of Cancer Therapy - Hepatitis [FACT-Hep] version 4) between baseline measures and assessment during treatment course between by treatment arms.

V. Focused evaluation of toxicities that are of interest for older patients including:

peripheral neuropathy, fatigue, falls, emergency room visits, hospitalization, treatment modification and discontinuation.

VI. Imaging correlative study objectives:

VIa. Evaluate the association between baseline and change during treatment of skeletal muscle index (SMI) and intermuscular adipose tissue (IMAT) and rates of grade 3 or higher chemotherapy toxicity experienced on treatment.

VIb. Evaluate the association between baseline and change during treatment of skeletal muscle index (SMI) and intermuscular adipose tissue (IMAT) and overall survival among older patients with metastatic pancreatic cancer.

VIc. Evaluate the association between baseline and change during treatment of skeletal muscle index (SMI) and intermuscular adipose tissue (IMAT) and geriatric assessment scores evaluating functional status.

VII. Laboratory correlative study objectives:

VIIa. Evaluation of the correlation between base line levels of biomarkers of aging (CRP and IL-6) and rates of grade 3 or higher chemotherapy toxicity during therapy.

VIIb. Evaluation of the correlation between changes in levels of CRP and IL-6 during therapy and rates of grade 3 chemotherapy toxicity.

VIIc. Evaluation of the correlation between baseline levels of biomarkers of aging (CRP and IL-6) and overall survival among older patients with metastatic pancreatic cancer.

VIId. Evaluation of the correlation between levels of baseline biomarkers of aging (CRP and IL-6) and geriatric assessments scores evaluation functional status.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive gemcitabine intravenously (IV) over 30 minutes and nab-paclitaxel IV over 30 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive fluorouracil IV over 46 hours starting on day 1. Patients also receive leucovorin IV over 90-120 minutes and liposomal irinotecan IV over 90 minutes on day

Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

184 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase II Study of Gemcitabine and Nab-Paclitaxel Compared With 5-Fluorouracil, Leucovorin, and Liposomal Irinotecan in Older Patients With Treatment Naïve Metastatic Pancreatic Cancer (GIANT)

Actual Study Start Date :

Jun 18, 2020

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (gemcitabine, nab-paclitaxel) Patients receive gemcitabine IV over 30 minutes and nab-paclitaxel IV over 30 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Drug: Gemcitabine Given IV Other Names: dFdC dFdCyd Difluorodeoxycytidine Drug: Gemcitabine Hydrochloride Given IV Other Names: dFdCyd Difluorodeoxycytidine Hydrochloride FF 10832 FF-10832 FF10832 Gemcitabine HCI Gemzar LY-188011 LY188011 Drug: Nab-paclitaxel Given IV Other Names: ABI 007 ABI-007 Abraxane Albumin-bound Paclitaxel Albumin-Stabilized Nanoparticle Paclitaxel Nanoparticle Albumin-bound Paclitaxel Nanoparticle Paclitaxel Paclitaxel Albumin paclitaxel albumin-stabilized nanoparticle formulation protein-bound paclitaxel Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies
Experimental: Arm B (fluorouracil, leucovorin, liposomal irinotecan) Patients receive fluorouracil IV over 46 hours starting on day 1. Patients also receive leucovorin IV over 90-120 minutes and liposomal irinotecan IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.	Drug: Fluorouracil Given IV Other Names: 5 Fluorouracil 5 Fluorouracilum 5 FU 5-Fluoro-2,4(1H, 3H)-pyrimidinedione 5-Fluorouracil 5-Fluracil 5-FU 5FU AccuSite Carac Fluoro Uracil Fluouracil Flurablastin Fluracedyl Fluracil Fluril Fluroblastin Ribofluor Ro 2-9757 Ro-2-9757 Drug: Leucovorin Given IV Other Names: Folinic acid Drug: Leucovorin Calcium Given IV Other Names: Adinepar Calcifolin Calcium (6S)-Folinate Calcium Folinate Calcium Leucovorin Calfolex Calinat Cehafolin Citofolin Citrec Citrovorum Factor Cromatonbic Folinico Dalisol Disintox Divical Ecofol Emovis Factor, Citrovorum Flynoken A Folaren Folaxin FOLI-cell Foliben Folidan Folidar Folinac Folinate Calcium folinic acid Folinic Acid Calcium Salt Pentahydrate Folinoral Folinvit Foliplus Folix Imo Lederfolat Lederfolin Leucosar leucovorin Rescufolin Rescuvolin Tonofolin Wellcovorin Drug: Liposomal Irinotecan Given IV Other Names: Irinotecan Liposome MM-398 nal-IRI Nanoliposomal Irinotecan Nanoparticle Liposome Formulation of Irinotecan Onivyde PEP02 Other: Quality-of-Life Assessment Ancillary studies Other Names: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies

Arm

Intervention/Treatment

Experimental: Arm A (gemcitabine, nab-paclitaxel)

Patients receive gemcitabine IV over 30 minutes and nab-paclitaxel IV over 30 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Drug: Gemcitabine

Given IV

Other Names:

dFdC

dFdCyd

Difluorodeoxycytidine

Drug: Gemcitabine Hydrochloride

Given IV

Other Names:

dFdCyd

Difluorodeoxycytidine Hydrochloride

FF 10832

FF-10832

FF10832

Gemcitabine HCI

Gemzar

LY-188011

LY188011

Drug: Nab-paclitaxel

Given IV

Other Names:

ABI 007

ABI-007

Abraxane

Albumin-bound Paclitaxel

Albumin-Stabilized Nanoparticle Paclitaxel

Nanoparticle Albumin-bound Paclitaxel

Nanoparticle Paclitaxel

Paclitaxel Albumin

paclitaxel albumin-stabilized nanoparticle formulation

protein-bound paclitaxel

Other: Quality-of-Life Assessment

Ancillary studies

Other Names:

Quality of Life Assessment

Other: Questionnaire Administration

Ancillary studies

Experimental: Arm B (fluorouracil, leucovorin, liposomal irinotecan)

Patients receive fluorouracil IV over 46 hours starting on day 1. Patients also receive leucovorin IV over 90-120 minutes and liposomal irinotecan IV over 90 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Drug: Fluorouracil

Given IV

Other Names:

5 Fluorouracil

5 Fluorouracilum

5 FU

5-Fluoro-2,4(1H, 3H)-pyrimidinedione

5-Fluorouracil

5-Fluracil

5-FU

5FU

AccuSite

Carac

Fluoro Uracil

Fluouracil

Flurablastin

Fluracedyl

Fluracil

Fluril

Fluroblastin

Ribofluor

Ro 2-9757

Ro-2-9757

Drug: Leucovorin

Given IV

Other Names:

Folinic acid

Drug: Leucovorin Calcium

Given IV

Other Names:

Adinepar

Calcifolin

Calcium (6S)-Folinate

Calcium Folinate

Calcium Leucovorin

Calfolex

Calinat

Cehafolin

Citofolin

Citrec

Citrovorum Factor

Cromatonbic Folinico

Dalisol

Disintox

Divical

Ecofol

Emovis

Factor, Citrovorum

Flynoken A

Folaren

Folaxin

FOLI-cell

Foliben

Folidan

Folidar

Folinac

Folinate Calcium

folinic acid

Folinic Acid Calcium Salt Pentahydrate

Folinoral

Folinvit

Foliplus

Folix

Imo

Lederfolat

Lederfolin

Leucosar

leucovorin

Rescufolin

Rescuvolin

Tonofolin

Wellcovorin

Drug: Liposomal Irinotecan

Given IV

Other Names:

Irinotecan Liposome

MM-398

nal-IRI

Nanoliposomal Irinotecan

Nanoparticle Liposome Formulation of Irinotecan

Onivyde

PEP02

Other: Quality-of-Life Assessment

Ancillary studies

Other Names:

Quality of Life Assessment

Other: Questionnaire Administration

Ancillary studies

Outcome Measures

Primary Outcome Measures

Overall survival (OS) [Up to 2 years post treatment]
Will use a stratified log rank test with one-sided alpha of 0.05 and 90% power. A truncated O'Brien-Fleming boundary will be used to control type I error for efficacy testing and repeated confidence interval methodology on the OS hazard ratio will be used for futility analyses

Secondary Outcome Measures

Instrumental Activities of Daily Living (IADL) [Up to 2 years post treatment]
Will evaluate the association between functional status as recorded by the IADL assessment tool and rates of grade 3 or higher chemotherapy toxicity within treatment arm. Will use logistic regression and a 0.025 level one-sided test for the odds ratio.

Other Outcome Measures

Progression-free survival (PFS) [Up to 2 years post treatment]
Objective tumor response [Up to 2 years post treatment]
Co-morbidities as a predictor of chemotherapy tolerance [Baseline up to time of disease evaluation, assessed up to 2 years]
Depression as a predictor of chemotherapy tolerance [Baseline up to time of disease evaluation, assessed up to 2 years]
Nutrition as a predictor of chemotherapy tolerance [Baseline up to time of disease evaluation, assessed up to 2 years]
Cognition as a predictor of chemotherapy tolerance [Baseline up to time of disease evaluation, assessed up to 2 years]
Change in functional status [Baseline up to time of disease evaluation, assessed up to 2 years]
Will evaluate the association between changes in functional status using a geriatric assessment, which will include the number of falls, cumulative illness rating scale, body mass index, weight loss and scores, such as the geriatric depression scale, and the blessed orientation memory concentration test. These will be treated as continuous measures as predictors of chemotherapy tolerance and will be assessed using a paired t-test. Longitudinal analyses will be conducted to evaluate the trajectory of patient-reported outcomes over time for each arm and to compare across the arms. Will explore the possibility that geriatric assessments at baseline that are prognostic for subsequent adverse events of interest, and will perform regression models for key adverse events (logistic, Poisson or linear regression as appropriate) to assess the relative predictive ability of the proposed geriatric assessments over those traditionally used to identify patients at risk.
Comprehensive Geriatric Assessment (CGA) domains [Baseline up to time of disease evaluation, assessed up to 2 years]
Will evaluate the correlation between CGA domains and overall survival by treatment arm.
Quality of life scores [Baseline up to time of disease evaluation, assessed up to 2 years]
Will be assessed as a continuous variable by the Functional Assessment of Cancer Treatment - Hepatitis version 4 between baseline measures and assessment during treatment course by treatment arms.
Incidence of toxicities in older patients [Up to 2 years post treatment]
Will include peripheral neuropathy grade 2 or higher, fatigue grade 3 or higher, falls, emergency room visits, hospitalization, treatment modification and discontinuation. These data will be obtained and recorded by the study nurse while conducting the patient's toxicity evaluation using the National Cancer Institute Common Terminology Criteria for Adverse Events.
Rate of grade 3 or higher chemotherapy toxicity experienced on treatment [Baseline up to time of disease evaluation, assessed up to 2 years]
Will evaluate the association between skeletal muscle index (SMI) and intermuscular adipose tissue (IMAT) and rate of grade 3 or higher chemotherapy toxicity. In a preliminary analysis, the longitudinal course of SMI and IMAT will be examined graphically and use longitudinal regression modeling to account for correlations due to the repeated assessments. The main analysis will utilize logistic regression modeling. Models will be fitted first with only the baseline values of SMI and IMAT and subsequently will be elaborated to include both baseline and change from baseline. The models will control for sociodemographic and clinical status measures at baseline and will also consider interactions between the two imaging-based markers
OS [Baseline up to time of disease evaluation, assessed up to 2 years]
Will evaluate the association between SMI and IMAT and OS. In a preliminary analysis, the longitudinal course of SMI and IMAT will be examined graphically and use Cox regression modeling to account for correlations due to the repeated assessments. The main analysis will utilize logistic regression modeling. Models will be fitted first with only the baseline values of SMI and IMAT and subsequently will be elaborated to include both baseline and change from baseline. The models will control for sociodemographic and clinical status measures at baseline and will also consider interactions between the two imaging-based markers.
Geriatric assessment scores [Baseline up to time of disease evaluation, assessed up to 2 years]
Will evaluate the association between skeletal muscle index (SMI) and intermuscular adipose tissue (IMAT) and geriatric assessment scores evaluating functional status. In a preliminary analysis, the longitudinal course of SMI and IMAT will be examined graphically and linear regression modeling to account for correlations due to the repeated assessments. The main analysis will utilize logistic regression modeling. Models will be fitted first with only the baseline values of SMI and IMAT and subsequently will be elaborated to include both baseline and change from baseline. The models will control for sociodemographic and clinical status measures at baseline and will also consider interactions between the two imaging-based markers
Toxicity and biomarkers of aging (CRP and IL-6) [Baseline up to time of disease evaluation, assessed up to 2 years]
Will evaluate the association between biomarkers of aging (CRP and IL-6) and rates of grade 3 or higher chemotherapy toxicity. Will be analyzed as continuous variables and correlated with clinical outcomes. Analysis of interaction with treatment arm will be performed but power for these effects is lower as the study is not designed to detect interactions. Logistic regression will be used to determine if levels of these biomarkers serve as predictors of toxicity or binary measures of efficacy (response).
Changes in levels of CRP and IL-6 and toxicity [Baseline up to time of disease evaluation, assessed up to 2 years]
Will evaluate the association correlation between changes in levels of CRP and IL-6 and rates of grade 3 chemotherapy toxicity. Will be analyzed as continuous variables and correlated with clinical outcomes. Analysis of interaction with treatment arm will be performed but power for these effects is lower as the study is not designed to detect interactions. Logistic regression will be used to determine if levels of these biomarkers serve as predictors of toxicity or binary measures of efficacy (response).
OS and biomarkers of aging (CRP and IL-6) [Baseline up to time of disease evaluation, assessed up to 2 years]
Will evaluate the association correlation between changes in levels of CRP and IL-6 and overall survival. Will be analyzed as continuous variables and correlated with clinical outcomes. Analysis of interaction with treatment arm will be performed but power for these effects is lower as the study is not designed to detect interactions. Standard time to event analyses (Kaplan-Meier curves and Cox models) will be used to determine association of biomarkers with PFS and OS.
Geriatric assessment scores and biomarkers of aging (CRP and IL-6) [Baseline up to time of disease evaluation, assessed up to 2 years]
Will evaluate the association correlation between levels of CRP and IL-6 and geriatric assessments scores evaluation functional status. Will be analyzed as continuous variables and correlated with clinical outcomes. Analysis of interaction with treatment arm will be performed but power for these effects is lower as the study is not designed to detect interactions. Logistic regression will be used to determine if levels of these biomarkers serve as predictors of toxicity or binary measures of efficacy (response).

Eligibility Criteria

Criteria

Ages Eligible for Study:

70 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Newly diagnosed untreated metastatic adenocarcinoma of the pancreas. However, previous surgery, adjuvant chemotherapy and/or radiation therapy will be allowed, provided radiation therapy is completed at least 2 weeks prior to registration and adjuvant therapy was administered more than 6 months prior to registration. Patients with the following histology are excluded: acinar cell; adenosquamous carcinoma
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Patient is an English speaker with the ability to understand and complete the informed consent and questionnaires
Leukocytes >= 3,000/mcL (obtained within 4 weeks of registration)
Absolute neutrophil count >= 1,500/mcL (obtained within 4 weeks of registration)
Platelets >= 100,000/mcL (obtained within 4 weeks of registration)
Total bilirubin =< institutional upper limit of normal (ULN) (obtained within 4 weeks of registration)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained within 4 weeks of registration)
Creatinine =< institutional ULN unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2 (obtained within 4 weeks of registration)
Glomerular filtration rate (GFR) >= 40 mL/min/1.73 m^{2 unless data exists supporting
safe use at lower kidney function values, no lower than 30 mL/min/1.73 m}2 (obtained within 4 weeks of registration)
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this protocol. HIV positive (+) patients who are on ritonavir or/and cobicistat-based regimen must be switched to alternative anti-retroviral therapy (ART)
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Male patients must agree not to father children while on study
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this protocol, patients should be class 2B or better
Patients must have measurable disease and scans must be done within 4 weeks of registration
Patients classified to have mild-moderate abnormalities in any of the domains evaluated in the screening geriatric assessment and are classified as "vulnerable" are eligible. Patients classified without any abnormalities ("fit") or with severe cognitive/functional impairment or high co-morbidity score ("frail") on the screening geriatric assessment are ineligible
Patients must agree not to take any medications or substances that are strong inhibitors or inducers of CYP3A4. Those who are randomized to liposomal irinotecan treatment arm should avoid drugs that are UGT1A1 inhibitors

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
2	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho	United States	83605
3	Kootenai Medical Center	Coeur d'Alene	Idaho	United States	83814
4	Walter Knox Memorial Hospital	Emmett	Idaho	United States	83617
5	Idaho Urologic Institute-Meridian	Meridian	Idaho	United States	83642
6	Saint Alphonsus Medical Center-Nampa	Nampa	Idaho	United States	83686
7	Kootenai Cancer Center	Post Falls	Idaho	United States	83854
8	Kootenai Cancer Clinic	Sandpoint	Idaho	United States	83864
9	Community Hospital of Anaconda	Anaconda	Montana	United States	59711
10	Billings Clinic Cancer Center	Billings	Montana	United States	59101
11	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
12	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
13	Great Falls Clinic	Great Falls	Montana	United States	59405
14	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
15	Community Medical Hospital	Missoula	Montana	United States	59804
16	Strecker Cancer Center-Belpre	Belpre	Ohio	United States	45714
17	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
18	Mount Carmel East Hospital	Columbus	Ohio	United States	43213
19	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio	United States	43214
20	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
21	Grant Medical Center	Columbus	Ohio	United States	43215
22	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
23	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
24	Doctors Hospital	Columbus	Ohio	United States	43228
25	Delaware Health Center-Grady Cancer Center	Delaware	Ohio	United States	43015
26	Grady Memorial Hospital	Delaware	Ohio	United States	43015
27	Dublin Methodist Hospital	Dublin	Ohio	United States	43016
28	Central Ohio Breast and Endocrine Surgery	Gahanna	Ohio	United States	43230
29	Mount Carmel Grove City Hospital	Grove City	Ohio	United States	43123
30	Fairfield Medical Center	Lancaster	Ohio	United States	43130
31	OhioHealth Mansfield Hospital	Mansfield	Ohio	United States	44903
32	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
33	OhioHealth Marion General Hospital	Marion	Ohio	United States	43302
34	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
35	Licking Memorial Hospital	Newark	Ohio	United States	43055
36	Newark Radiation Oncology	Newark	Ohio	United States	43055
37	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
38	Saint Ann's Hospital	Westerville	Ohio	United States	43081
39	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
40	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon	United States	97814
41	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon	United States	97914
42	Billings Clinic-Cody	Cody	Wyoming	United States	82414
43	Welch Cancer Center	Sheridan	Wyoming	United States	82801