Gemcitabine Hydrochloride and Cisplatin in Treating Participants With Invasive Bladder Urothelial Cancer
Status: | Recruiting |
---|---|
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 2/23/2019 |
Start Date: | August 1, 2018 |
End Date: | February 2029 |
Contact: | Gopa Iyer, MD |
Email: | iyerg@mskcc.org |
Phone: | 646-888-4737 |
A Phase II Study of Dose-Dense Gemcitabine Plus Cisplatin (ddGC) in Patients With Muscle-Invasive Bladder Cancer With Bladder Preservation for Those Patients Whose Tumors Harbor Deleterious DNA Damage Response (DDR) Gene Alterations
This phase II trial studies how well gemcitabine hydrochloride and cisplatin work in treating
participants with invasive bladder urothelial cancer. Drugs used in chemotherapy, such as
gemcitabine hydrochloride and cisplatin, 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.
participants with invasive bladder urothelial cancer. Drugs used in chemotherapy, such as
gemcitabine hydrochloride and cisplatin, 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.
PRIMARY OBJECTIVES:
I. To determine the 3-year event free survival, defined as the proportion of patients without
invasive or metastatic recurrence following definitive dose dense gemcitabine hydrochloride
(gemcitabine) and cisplatin chemotherapy in those patients whose pre-treatment transurethral
resection of bladder tumor (TURBT) tumors harbor deleterious DDR gene alterations and who
achieve < cT1 response to chemotherapy.
SECONDARY OBJECTIVES:
I. To determine the clinical response rate (< cT1) for patients harboring deleterious DDR
gene alterations following dose dense gemcitabine and cisplatin.
II. To determine the bladder-intact and overall survival for DDR-altered patients with < cT1.
III. For DDR gene altered patients who elect radical cystectomy despite < cT1, to determine
the pT0 rate in this patient population.
IV. To determine the pathologic response rate at cystectomy and 3-year recurrence-free and
overall survival for patients without DDR mutations who are registered onto this trial.
V. To assess the local treatment burden (Bacillus Calmette-Guerin [BCG] therapy, resection of
non-invasive disease) over time in the bladder-sparing group.
OUTLINE:
Participants receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on day 1,
cisplatin IV on days 1 and 2, and pegfilgrastim subcutaneously (SC) on day 3. Treatment
repeats every 14 days for up to 6 courses in the absence of disease progression or unaccepted
toxicity. Participants are then assigned to 1 of 2 arms.
ARM I: Participants with DDR gene alteration and disease stage < cT1 undergo bladder sparing.
ARM II: Participants with DDR gene alteration and disease stage >= cT1 or participants
without DDR gene alteration undergo radical cystectomy or chemoradiotherapy.
After completion of study treatment, participants are followed up for 5 years.
I. To determine the 3-year event free survival, defined as the proportion of patients without
invasive or metastatic recurrence following definitive dose dense gemcitabine hydrochloride
(gemcitabine) and cisplatin chemotherapy in those patients whose pre-treatment transurethral
resection of bladder tumor (TURBT) tumors harbor deleterious DDR gene alterations and who
achieve < cT1 response to chemotherapy.
SECONDARY OBJECTIVES:
I. To determine the clinical response rate (< cT1) for patients harboring deleterious DDR
gene alterations following dose dense gemcitabine and cisplatin.
II. To determine the bladder-intact and overall survival for DDR-altered patients with < cT1.
III. For DDR gene altered patients who elect radical cystectomy despite < cT1, to determine
the pT0 rate in this patient population.
IV. To determine the pathologic response rate at cystectomy and 3-year recurrence-free and
overall survival for patients without DDR mutations who are registered onto this trial.
V. To assess the local treatment burden (Bacillus Calmette-Guerin [BCG] therapy, resection of
non-invasive disease) over time in the bladder-sparing group.
OUTLINE:
Participants receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on day 1,
cisplatin IV on days 1 and 2, and pegfilgrastim subcutaneously (SC) on day 3. Treatment
repeats every 14 days for up to 6 courses in the absence of disease progression or unaccepted
toxicity. Participants are then assigned to 1 of 2 arms.
ARM I: Participants with DDR gene alteration and disease stage < cT1 undergo bladder sparing.
ARM II: Participants with DDR gene alteration and disease stage >= cT1 or participants
without DDR gene alteration undergo radical cystectomy or chemoradiotherapy.
After completion of study treatment, participants are followed up for 5 years.
Inclusion Criteria:
- Step 1 Patient Registration Eligibility Criteria
- Histologically confirmed muscle-invasive urothelial carcinoma of the bladder.
Urothelial carcinoma invading into the prostatic stroma with no histologic muscle
invasion is allowed, provided the extent of disease is confirmed via imaging and/or
examination under anesthesia (EUA). The diagnostic TURBT sample must have been
obtained within 60 days prior to registration
- 20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE)
pre-treatment diagnostic transurethral resection (TUR) specimen available (for
sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a
total of 22 unstained slides. An FFPE block is also acceptable
- Clinical stage T2-T4aN0/xM0 disease
- Medically appropriate candidate for radical cystectomy as assessed by surgeon
- No concomitant multifocal carcinoma in situ; a single focus is allowed
- One focus of muscle-invasive bladder cancer and/or a tumor < 5 cm in size
- No clinical or radiographic evidence for locally advanced or metastatic disease
- No prior anti-PD-1, anti PD-L1 therapies, or systemic chemotherapy (prior intravesical
induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x 6
treatments; BCG refractory disease, defined as disease recurrence within 3 months of
BCG therapy, is not allowed)
- No prior radiation therapy to the bladder
- No major surgery or radiation therapy =< 4 weeks of registration
- Not pregnant and not nursing. This study involves an agent that has known genotoxic,
mutagenic and teratogenic effects. 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
- Absolute neutrophil count (ANC) >= 1,000/mm^3
- Platelet count >= 100,000/mm^3
- Calculated creatinine clearance >= 55 mL/min
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
* (For patients with documented Gilbert's syndrome bilirubin =< 3 x ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
- Alkaline phosphatase =< 2.5 x ULN
- No hydronephrosis refractory to urinary diversion
- No evidence of New York Heart Association (NYHA) functional class III or IV heart
disease
- No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology
Criteria for Adverse Events (CTCAE) version 5.0 grade >= 2
- No pre-existing sensory grade >= 2 neuropathy
- No pre-existing grade >= 2 hearing loss
- No serious intercurrent medical or psychiatric illness, including serious active
infection
- None of the following within the 6 months prior to study drug administration:
myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass
graft, symptomatic congestive heart failure, cerebrovascular accident, or transient
ischemic attack
- No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness or other active infection. HIV-positive patients on combination
antiretroviral therapy are ineligible because of the potential for pharmacokinetic
interactions with the drugs used in this trial. In addition, these patients are at
increased risk of lethal infections when treated with marrow-suppressive therapy.
Appropriate studies will be undertaken in patients receiving combination
antiretroviral therapy, when indicated
- No history of allergic reaction attributed to compounds of similar chemical or
biologic composition to the agents used in this study
- No concurrent treatment on another clinical trial; supportive care trials or
non-therapeutic trials (e.g., quality of life) are allowed
- No prior malignancy except for: adequately treated basal or squamous cell skin cancer,
in situ cervical cancer, adequately treated stage I or II cancer from which the
patient is currently in complete remission, or any other cancer from which the patient
has been disease free for five years. Patients with localized prostate cancer who are
being followed by an active surveillance program are also eligible
- Step 2 Patient Registration Eligibility Criteria
- Patients must have completed 4 or more cycles of protocol-directed chemotherapy
- Step 3 Patient Registration Eligibility Criteria (only patients with a DDR gene
alteration)
- Deleterious alteration within 1 or more of 9 pre-defined DDR genes within the
pre-treatment TURBT deoxyribonucleic acid (DNA)
- Cystoscopy and imaging performed to determine stage/treatment assignment
We found this trial at
283
sites
1755 59th Place
West Des Moines, Iowa 50266
West Des Moines, Iowa 50266
(515) 358-8000
Principal Investigator: Richard L. Deming
Phone: 308-398-6518
Mercy Medical Center-West Lakes Mercy Medical Center-West Lakes is a 146-bed, full-service community hospital situated...
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2545 Schoenersville Rd
Bethlehem, Pennsylvania 18017
Bethlehem, Pennsylvania 18017
(484) 884-2200
Principal Investigator: Tareq Al Baghdadi
Phone: 734-712-3671
Lehigh Valley Hospital - Muhlenberg At Lehigh Valley Health Network, we continually go the extra...
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Bremerton, Washington 98310
Principal Investigator: Richard L. Deming
Phone: 308-398-6518
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666 Elm Street
Buffalo, New York 14263
Buffalo, New York 14263
(716) 845-2300
Principal Investigator: Ellis G. Levine
Phone: 800-767-9355
Roswell Park Cancer Institute Welcome to Roswell Park Cancer Institute (RPCI), America's first cancer center...
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1 Hurley Plaza
Flint, Michigan 48503
Flint, Michigan 48503
(810) 262-9000
Principal Investigator: Tareq Al Baghdadi
Phone: 734-712-3671
Hurley Medical Center From its founding in 1908, Hurley Medical Center has devoted itself to...
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Allentown, Pennsylvania 18103
Principal Investigator: Tareq Al Baghdadi
Phone: 734-712-3671
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5301 McAuley Drive
Ann Arbor, Michigan 48197
Ann Arbor, Michigan 48197
734-712-3456
Principal Investigator: Tareq Al Baghdadi
Phone: 734-712-3671
Saint Joseph Mercy Hospital St. Joseph Mercy Ann Arbor Hospital is a 537-bed teaching hospital...
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1625 Maple Lane
Ashland, Wisconsin 54806
Ashland, Wisconsin 54806
Principal Investigator: Bret E. Friday
Phone: 218-786-3308
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Ashland, Wisconsin 54806
Principal Investigator: Bret E. Friday
Phone: 218-786-3308
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Basking Ridge, New Jersey 07920
Principal Investigator: Gopakumar V. Iyer
Phone: 212-639-5007
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3535 Pentagon Boulevard
Beavercreek, Ohio 45431
Beavercreek, Ohio 45431
Principal Investigator: Howard M. Gross
Phone: 937-775-1350
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Bemidji, Minnesota 56601
Principal Investigator: Preston D. Steen
Phone: 218-333-5000
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Billings, Montana 59101
Principal Investigator: Benjamin T. Marchello
Phone: 800-996-2663
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300 N. Seventh St.
Bismarck, North Dakota 58501
Bismarck, North Dakota 58501
(701) 323-6000
Principal Investigator: Preston D. Steen
Phone: 701-323-5760
Sanford Bismarck Medical Center Whether your stay in our hospital is one day for same...
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Illinois CancerCare-Bloomington Illinois CancerCare, P.C. is a comprehensive practice treating patients withcancer andblood diseases. Our...
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Boise, Idaho 83706
Principal Investigator: Benjamin T. Marchello
Phone: 734-712-3671
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Bonne Terre, Missouri 63628
Principal Investigator: Bryan A. Faller
Phone: 314-996-5569
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915 Highland Blvd
Bozeman, Montana 59715
Bozeman, Montana 59715
(406) 414-5000
Principal Investigator: Benjamin T. Marchello
Phone: 406-969-6060
Bozeman Deaconess Hospital Bozeman Deaconess Hospital is a Joint Commission certified, licensed Level III trauma...
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Brainerd, Minnesota 56401
Principal Investigator: Bret E. Friday
Phone: 773-702-9171
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Bremerton, Washington 98310
Principal Investigator: Richard L. Deming
Phone: 308-398-6518
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Bridgeport, West Virginia 26330
Principal Investigator: Malcolm D. Mattes
Phone: 304-293-7374
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Bryan, Texas 77802
Principal Investigator: Richard L. Deming
Phone: 308-398-6518
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Burien, Washington 98166
Principal Investigator: Richard L. Deming
Phone: 308-398-6518
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201 E Nicollet Blvd
Burnsville, Minnesota 55337
Burnsville, Minnesota 55337
(952) 892-2000
Principal Investigator: Daniel M. Anderson
Phone: 952-993-1517
Fairview Ridges Hospital Fairview Ridges Hospital is a 150-bed, Level III Trauma Care facility, offering...
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3123 Medical Dr
Caldwell, Idaho 83605
Caldwell, Idaho 83605
Principal Investigator: Benjamin T. Marchello
Phone: 734-712-3671
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Illinois CancerCare - Canton Illinois CancerCare is one of the largest private oncology and hematology...
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211 Saint Francis Drive
Cape Girardeau, Missouri 63703
Cape Girardeau, Missouri 63703
573-331-3000
Principal Investigator: Bryan A. Faller
Phone: 573-334-2230
Saint Francis Medical Center Saint Francis Medical Center is a 282-bed facility serving more than...
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789 Mt Auburn Rd
Cape Girardeau, Missouri 63703
Cape Girardeau, Missouri 63703
(573) 519-4725
Principal Investigator: Bryan A. Faller
Phone: 573-651-5550
Southeast Cancer Center SoutheastHEALTH is a far-reaching network of providers and facilities including Southeast Hospital...
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Carbondale, Illinois 62902
Principal Investigator: Bryan A. Faller
Phone: 618-457-5200
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Carterville, Illinois 62918
Principal Investigator: Bryan A. Faller
Phone: 618-985-3333
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Illinois CancerCare - Carthage Illinois CancerCare, P.C. is a comprehensive practice treating patients withcancer andblood...
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Centerville, Ohio 45459
Principal Investigator: Howard M. Gross
Phone: 937-775-1350
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Centerville, Ohio 45459
Principal Investigator: Howard M. Gross
Phone: 937-775-1350
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Centralia, Illinois 62801
Principal Investigator: Bryan A. Faller
Phone: 217-876-4740
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Chattanooga, Tennessee 37404
Principal Investigator: Richard L. Deming
Phone: 308-398-6518
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Cincinnati, Ohio 45220
Principal Investigator: Richard L. Deming
Phone: 308-398-6518
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Cincinnati, Ohio 45236
Principal Investigator: Howard M. Gross
Phone: 937-775-1350
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Cincinnati, Ohio 45242
Principal Investigator: Richard L. Deming
Phone: 308-398-6518
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Clive, Iowa 50325
Principal Investigator: Richard L. Deming
Phone: 308-398-6518
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12495 University Ave
Clive, Iowa 50325
Clive, Iowa 50325
(515) 358-9700
Principal Investigator: Richard L. Deming
Phone: 308-398-6518
Mercy Cancer Center - West Lakes When it comes to cancer care, there
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6001 E Woodmen Rd
Colorado Springs, Colorado 80923
Colorado Springs, Colorado 80923
(719) 776-5000
Principal Investigator: Richard L. Deming
Phone: 308-398-6518
Penrose-Saint Francis Healthcare Founded by the Sisters of St. Francis and the Sisters of Charity,...
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Colorado Springs, Colorado 80907
Principal Investigator: Richard L. Deming
Phone: 308-398-6518
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Commack, New York 11725
Principal Investigator: Gopakumar V. Iyer
Phone: 631-623-4000
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4050 Coon Rapids Blvd NW
Coon Rapids, Minnesota 55433
Coon Rapids, Minnesota 55433
(763) 236-6000
Principal Investigator: Daniel M. Anderson
Phone: 952-993-1517
Mercy Hospital Mercy Hospital, located in Coon Rapids, Minnesota, is a 271-bed non-profit hospital that...
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10 Barnes West Drive
Creve Coeur, Missouri 63141
Creve Coeur, Missouri 63141
Principal Investigator: Vivek K. Arora
Phone: 800-600-3606
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2222 Philadelphia Dr
Dayton, Ohio 45406
Dayton, Ohio 45406
(937) 734-2612
Principal Investigator: Howard M. Gross
Phone: 937-775-1350
Good Samaritan Hospital - Dayton Good Samaritan Hospital (GSH) is passionate about providing the most...
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1 Wyoming St,
Dayton, Ohio 45409
Dayton, Ohio 45409
(937) 208-8000
Principal Investigator: Howard M. Gross
Phone: 937-775-1350
Miami Valley Hospital Miami Valley Hospital (MVH) is passionate about providing the most recent medical...
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Dayton, Ohio 45415
Principal Investigator: Howard M. Gross
Phone: 937-832-1093
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Dayton, Ohio 45415
Principal Investigator: Howard M. Gross
Phone: 937-775-1350
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210 West McKinley Avenue
Decatur, Illinois 62526
Decatur, Illinois 62526
Principal Investigator: Bryan A. Faller
Phone: 217-876-4740
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2300 N Edward St
Decatur, Illinois 62526
Decatur, Illinois 62526
(217) 876-8121
Principal Investigator: Bryan A. Faller
Phone: 217-876-4740
Decatur Memorial Hospital An American flag bearing only 48 stars waved above Decatur Memorial Hospital...
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115 10th Avenue Northeast
Deer River, Minnesota 56636
Deer River, Minnesota 56636
Principal Investigator: Bret E. Friday
Phone: 218-786-3308
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2525 S Downing St
Denver, Colorado 80210
Denver, Colorado 80210
(303) 778-1955
Principal Investigator: Richard L. Deming
Phone: 308-398-6518
Porter Adventist Hospital Founded in 1930, Porter Adventist Hospital has provided people throughout Denver and...
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1200 Pleasant St
Des Moines, Iowa 50309
Des Moines, Iowa 50309
(515) 241-6212
Principal Investigator: Robert J. Behrens
Phone: 515-241-6727
Iowa Methodist Medical Center Iowa Methodist Medical Center was established in 1901 in a single...
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Des Moines, Iowa 50309
Principal Investigator: Robert J. Behrens
Phone: 515-282-2921
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Des Moines, Iowa 50314
Principal Investigator: Robert J. Behrens
Phone: 515-282-2200
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700 E University Ave
Des Moines, Iowa 50316
Des Moines, Iowa 50316
(515) 263-5612
Principal Investigator: Robert J. Behrens
Phone: 515-241-8704
Iowa Lutheran Hospital Iowa Lutheran Hospital has a long history of serving the Des Moines...
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Des Moines, Iowa 50314
Principal Investigator: Richard L. Deming
Phone: 308-398-6518
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1111 6th Ave
Des Moines, Iowa 50314
Des Moines, Iowa 50314
(515) 247-3121
Principal Investigator: Richard L. Deming
Phone: 308-398-6518
Mercy Medical Center - Des Moines Mercy Medical Center
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Detroit, Michigan 48236
Principal Investigator: Tareq Al Baghdadi
Phone: 734-712-3671
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1027 Washington Avenue
Detroit Lakes, Minnesota 56501
Detroit Lakes, Minnesota 56501
Principal Investigator: Bret E. Friday
Phone: 773-702-9171
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Duluth, Minnesota 55805
Principal Investigator: Bret E. Friday
Phone: 218-786-3308
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Duluth, Minnesota 55805
Principal Investigator: Bret E. Friday
Phone: 888-203-7267
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Duluth, Minnesota 55805
Principal Investigator: Bret E. Friday
Phone: 218-786-3308
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17900 23 Mile Road
East China Township, Michigan 48054
East China Township, Michigan 48054
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East Stroudsburg, Pennsylvania 18301
Principal Investigator: Tareq Al Baghdadi
Phone: 570-422-1700
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2200 Craig Road
Eau Claire, Wisconsin 54701
Eau Claire, Wisconsin 54701
Principal Investigator: Dean A. Delmastro
Phone: 800-782-8581
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6401 France Ave S
Edina, Minnesota 55435
Edina, Minnesota 55435
(952) 924-5000
Principal Investigator: Daniel M. Anderson
Phone: 952-993-1517
Fairview Southdale Hospital Fairview Health Services is an award-winning nonprofit health care system based in...
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Effingham, Illinois 62401
Principal Investigator: Bryan A. Faller
Phone: 217-876-4740
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350 Engle St
Englewood, New Jersey 07631
Englewood, New Jersey 07631
(201) 894-3000
Principal Investigator: Brian H. Kim
Phone: 201-894-3456
Englewood Hospital and Medical Center Englewood Hospital was incorporated in 1888 as a non-profit, non-sectarian...
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Illinois CancerCare - Eureka Illinois CancerCare is one of the largest private oncology and hematology...
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801 Broadway North
Fargo, North Dakota 58122
Fargo, North Dakota 58122
Principal Investigator: Preston D. Steen
Phone: 800-437-4010
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Sanford Medical Center-Fargo Sanford Medical Center Fargo is a major medical center that provides comprehensive,...
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820 4th St N
Fargo, North Dakota 58102
Fargo, North Dakota 58102
(701) 234-6161
Principal Investigator: Preston D. Steen
Phone: 701-234-6161
Roger Maris Cancer Center Sanford Health is an integrated health system headquartered in the Dakotas...
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