Transoral Surgery Followed By Low-Dose or Standard-Dose Radiation Therapy With or Without Chemotherapy in Treating Patients With HPV Positive Stage III-IVA Oropharyngeal Cancer
Status: | Active, not recruiting |
---|---|
Conditions: | Cancer, Infectious Disease, Women's Studies |
Therapuetic Areas: | Immunology / Infectious Diseases, Oncology, Reproductive |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 8/3/2018 |
Start Date: | August 2013 |
End Date: | February 2023 |
Phase II Randomized Trial of Transoral Surgical Resection Followed by Low-Dose or Standard-Dose IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer
This randomized phase II trial studies how well transoral surgery followed by low-dose or
standard-dose radiation therapy works in treating patients with human papilloma virus (HPV)
positive stage III-IVA oropharyngeal cancer. Radiation therapy uses high-energy x-rays to
kill tumor cells. Drugs used in chemotherapy work in different ways to stop the growth of
tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation
therapy with chemotherapy may kill any tumor cells that remain after surgery. It is not yet
known how much extra treatment needs to be given after surgery.
standard-dose radiation therapy works in treating patients with human papilloma virus (HPV)
positive stage III-IVA oropharyngeal cancer. Radiation therapy uses high-energy x-rays to
kill tumor cells. Drugs used in chemotherapy work in different ways to stop the growth of
tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation
therapy with chemotherapy may kill any tumor cells that remain after surgery. It is not yet
known how much extra treatment needs to be given after surgery.
PRIMARY OBJECTIVES:
I. Accrual, risk distribution, and surgical quality will be used to determine the feasibility
of a prospective multi-institutional study of transoral surgery for HPV positive (+)
oropharynx cancer followed by risk-adjusted adjuvant therapy.
II. To assess the oncologic efficacy following transoral resection and adjuvant therapy in
patients determined to be at "intermediate risk" after surgical excision, the 2-year
progression free survival (PFS) rate will be examined.
SECONDARY OBJECTIVES:
I. To estimate the patient distribution with various histologic risk features. II. To assess
and compare early and late toxicities associated with transoral surgery (TOS) and the
different doses of adjuvant postoperative radiotherapy (PORT).
III. To evaluate swallowing function before and after TOS and risk-adjusted adjuvant therapy.
IV. To evaluate quality of life (QOL), swallowing perception and performance, voice outcomes,
and head and neck symptoms.
TERTIARY OBJECTIVES:
I. To correlate tumor TP53 mutation and other associated mutation profile with pathologic
findings, with PFS and other outcome parameters in patients with resectable HPV-associated
oropharyngeal squamous cell carcinoma (OPSCC) after the above treatments.
II. To evaluate radiation resistance markers, including excision repair cross complementing 1
(ERCC1) single nucleotide polymorphism and protein expression, and correlate them with
treatment efficacy.
III. To investigate the usefulness of biomarkers in predicting progression-free survival and
biomarkers, including tumor ERCC1, epidermal growth factor receptor (EGFR), plasma
cytokine/chemokines, cellular immunity to HPV, and oral HPV deoxyribonucleic acid (DNA).
OUTLINE: Patients are classified by risk status (low risk, intermediate risk, or high risk)
and assigned to the appropriate treatment group. Patients classified as intermediate risk are
randomized to 1 or 2 treatment arms.
ARM A (low risk): Patients undergo transoral surgical resection of the oropharyngeal tumor.
ARM B (intermediate risk): Patients undergo transoral surgical resection of the oropharyngeal
tumor. Patients then undergo low-dose intensity modulated radiation therapy (IMRT) once daily
(QD) five days a week for 5 weeks.
ARM C (intermediate risk): Patients undergo transoral surgical resection of the oropharyngeal
tumor. Patients then undergo standard-dose IMRT QD five days a week for 6 weeks.
ARM D (high risk): Patients undergo transoral surgical resection of the oropharyngeal tumor.
Patients then undergo standard-dose IMRT QD five days a week for 6-7 weeks. Patients also
receive cisplatin intravenously (IV) over 60 minutes or carboplatin IV over 30 minutes on
days 1, 8, 15, 22, 29, 36, and 43 during radiation therapy.
After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 1 year.
I. Accrual, risk distribution, and surgical quality will be used to determine the feasibility
of a prospective multi-institutional study of transoral surgery for HPV positive (+)
oropharynx cancer followed by risk-adjusted adjuvant therapy.
II. To assess the oncologic efficacy following transoral resection and adjuvant therapy in
patients determined to be at "intermediate risk" after surgical excision, the 2-year
progression free survival (PFS) rate will be examined.
SECONDARY OBJECTIVES:
I. To estimate the patient distribution with various histologic risk features. II. To assess
and compare early and late toxicities associated with transoral surgery (TOS) and the
different doses of adjuvant postoperative radiotherapy (PORT).
III. To evaluate swallowing function before and after TOS and risk-adjusted adjuvant therapy.
IV. To evaluate quality of life (QOL), swallowing perception and performance, voice outcomes,
and head and neck symptoms.
TERTIARY OBJECTIVES:
I. To correlate tumor TP53 mutation and other associated mutation profile with pathologic
findings, with PFS and other outcome parameters in patients with resectable HPV-associated
oropharyngeal squamous cell carcinoma (OPSCC) after the above treatments.
II. To evaluate radiation resistance markers, including excision repair cross complementing 1
(ERCC1) single nucleotide polymorphism and protein expression, and correlate them with
treatment efficacy.
III. To investigate the usefulness of biomarkers in predicting progression-free survival and
biomarkers, including tumor ERCC1, epidermal growth factor receptor (EGFR), plasma
cytokine/chemokines, cellular immunity to HPV, and oral HPV deoxyribonucleic acid (DNA).
OUTLINE: Patients are classified by risk status (low risk, intermediate risk, or high risk)
and assigned to the appropriate treatment group. Patients classified as intermediate risk are
randomized to 1 or 2 treatment arms.
ARM A (low risk): Patients undergo transoral surgical resection of the oropharyngeal tumor.
ARM B (intermediate risk): Patients undergo transoral surgical resection of the oropharyngeal
tumor. Patients then undergo low-dose intensity modulated radiation therapy (IMRT) once daily
(QD) five days a week for 5 weeks.
ARM C (intermediate risk): Patients undergo transoral surgical resection of the oropharyngeal
tumor. Patients then undergo standard-dose IMRT QD five days a week for 6 weeks.
ARM D (high risk): Patients undergo transoral surgical resection of the oropharyngeal tumor.
Patients then undergo standard-dose IMRT QD five days a week for 6-7 weeks. Patients also
receive cisplatin intravenously (IV) over 60 minutes or carboplatin IV over 30 minutes on
days 1, 8, 15, 22, 29, 36, and 43 during radiation therapy.
After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 1 year.
Inclusion Criteria:
- REGISTRATION TO SURGERY (ARM S)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Patients must have newly diagnosed, histologically or cytologically confirmed squamous
cell carcinoma or undifferentiated carcinoma of the oropharynx; patients must have
been determined to have resectable oropharyngeal disease; patients with primary tumor
or nodal metastasis fixed to the carotid artery, skull base or cervical spine are not
eligible
- Patients must have American Joint Committee on Cancer (AJCC) TNM tumor stage III, IV
a, or IV b (with no evidence of distant metastases) as determined by imaging studies
(performed < 4 weeks prior to pre-registration) and complete head and neck exam; the
following imaging is required: computed tomography (CT) scan with IV contrast or
magnetic resonance imaging (MRI)
- Patients must have biopsy-proven cyclin-dependent kinase inhibitor 2A (p16)+
oropharynx cancer; the histologic evidence of invasive squamous cell carcinoma may
have been obtained from the primary tumor or metastatic lymph node; it is required
that patients have nodal stage N1-N2b confirmed by clinical or radiographic methods
(clinically N0 patients are not eligible)
- Carcinoma of the oropharynx associated with HPV as determined by p16 protein
expression using immunohistochemistry (IHC) performed by a Clinical Laboratory
Improvement Amendments (CLIA) approved laboratory; using p16 antibody obtained from
Roche mtm laboratories AG (CINtec, clone E6H4) is recommended
- No prior radiation above the clavicles
- Patients with a history of a curatively treated malignancy must be disease-free for at
least two years except for carcinoma in situ of cervix and/or non-melanomatous skin
cancer
- Patients with the following within the last 6 months prior to pre-registration must be
evaluated by a cardiologist and/or neurologist prior to entry into the study
- Patients must not have evidence of extensive or "matted/fixed" pathologic adenopathy
on preoperative imaging
- Absolute neutrophil count >= 1,500/mm^3
- Platelets >= 100,000/mm^3
- Total bilirubin =< the upper limit of normal (ULN)
- Calculated creatinine clearance must be > 60 ml/min using the Cockcroft-Gault formula
- Women must not be pregnant or breast-feeding due to the teratogenicity of
chemotherapy; all females of childbearing potential must have a blood test or urine
study within 2 weeks prior to registration to rule out pregnancy; a female of
childbearing potential is any woman, regardless of sexual orientation or whether they
have undergone tubal ligation, who meets the following criteria: has not undergone a
hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for
at least 24 consecutive months (i.e., has had menses at any time in the preceding 24
consecutive months)
- Patient must not have an intercurrent illness likely to interfere with protocol
therapy or prevent surgical resection
- Patients must not have uncontrolled diabetes, uncontrolled infection despite
antibiotics or uncontrolled hypertension within 30 days prior to pre-registration
- REGISTRATION/RANDOMIZATION TO STEP 2 - ARMS A, B, C AND D AND REGISTRATION TO STEP 3
- Histopathologic assessment of surgical pathology must include examination for
perineural invasion (PNI) and lymphovascular invasion (LVI) and reported as absent or
present; the absence or presence of extracapsular extension (ECE) requires gross and
microscopic assessment and is defined to be:
- Absent (negative or nodal metastasis with smooth/rounded leading edge confined to
thickened capsule/pseudocapsule),
- Present - minimal (tumor extends =< 1 mm beyond the lymph node capsule), or
- Present - extensive (gross, tumor extends > 1 mm beyond the lymph node capsule
(includes soft tissue metastasis)
- Patients must have ECOG performance status 0 or 1
- Patient must be registered/randomized within 5-7 weeks following surgery
- Women of childbearing potential and sexually active males are strongly advised to use
an accepted and effective method of contraception
We found this trial at
58
sites
1500 E Duarte Rd
Duarte, California 91010
Duarte, California 91010
(626) 256-4673
Principal Investigator: Ellie G. Maghami
Phone: 800-826-4673
City of Hope Comprehensive Cancer Center City of Hope is a leading research and treatment...
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75 Francis street
Boston, Massachusetts 02115
Boston, Massachusetts 02115
(617) 732-5500
Principal Investigator: Tom Thomas
Phone: 617-724-5200
Brigham and Women's Hosp Boston’s Brigham and Women’s Hospital (BWH) is an international leader in...
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1300 Jefferson Park Avenue
Charlottesville, Virginia 22908
Charlottesville, Virginia 22908
434-243-6784
Principal Investigator: Mark J. Jameson
Phone: 434-243-6143
University of Virginia Cancer Center We are fortunate in having state of the art clinical...
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3300 Gallows Road
Falls Church, Virginia 22042
Falls Church, Virginia 22042
(703) 776-4001
Principal Investigator: John F. Deeken
Phone: 703-970-6431
Inova Fairfax Hospital Inova Fairfax Hospital, Inova's flagship hospital, is an 833-bed, nationally recognized regional...
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529 West Markham Street
Little Rock, Arkansas 72205
Little Rock, Arkansas 72205
(501) 686-7000
Principal Investigator: Rangaswamy Govindarajan
Phone: 501-686-8274
University of Arkansas for Medical Sciences The University of Arkansas for Medical Sciences (UAMS) in...
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3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
Portland, Oregon 97239
503 494-8311
Principal Investigator: Peter E. Andersen
Phone: 503-494-1080
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
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4805 Northeast Glisan Street
Portland, Oregon 97213
Portland, Oregon 97213
(503) 215-1111
Principal Investigator: Keith S. Lanier
Phone: 503-215-6412
Providence Portland Medical Center We strive to give those we serve exceptional, compassionate health care...
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Albuquerque, New Mexico 87131
(505) 277-0111
Principal Investigator: Andrew T. Cowan
Phone: 505-272-6972
University of New Mexico Founded in 1889 as New Mexico’s flagship institution, the University of...
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Atlanta, Georgia 30322
Principal Investigator: Nabil F. Saba
Phone: 404-778-1868
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550 Peachtree St NE
Atlanta, Georgia 30308
Atlanta, Georgia 30308
(404) 686-4411
Principal Investigator: Nabil F. Saba
Phone: 404-778-1868
Emory University Hospital Midtown Emory University Hospital Midtown is a 511-bed community-based, acute care teaching...
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6701 N Charles St
Baltimore, Maryland 21204
Baltimore, Maryland 21204
(443) 849-2000
Principal Investigator: Marshall A. Levine
Phone: 443-849-3706
Greater Baltimore Medical Center The 255-bed medical center (acute and sub-acute care) is located on...
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401 North Broadway
Baltimore, Maryland 21287
Baltimore, Maryland 21287
410-955-5000
Principal Investigator: Jeremy D. Richmon
Phone: 410-955-8804
Johns Hopkins University-Sidney Kimmel Cancer Center The name Johns Hopkins has become synonymous with excellence...
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Birmingham, Alabama 35233
Principal Investigator: Sharon A. Spencer
Phone: 205-934-0309
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450 Brookline Ave
Boston, Massachusetts 2215
Boston, Massachusetts 2215
617-632-3000
Principal Investigator: Tom Thomas
Phone: 617-724-5200
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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Boston, Massachusetts 02118
Principal Investigator: Scharukh Jalisi
Phone: 617-638-8265
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Boulder, Colorado 80303
Principal Investigator: Keren Sturtz
Phone: 888-785-6789
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171 Ashley Avenue
Charleston, South Carolina 29425
Charleston, South Carolina 29425
843-792-1414
Principal Investigator: Terry A. Day
Phone: 843-792-9321
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
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2049 E 100th St
Cleveland, Ohio 44106
Cleveland, Ohio 44106
(216) 444-2200
Principal Investigator: David J. Adelstein
Phone: 866-223-8100
Cleveland Clinic Foundation The Cleveland Clinic (formally known as The Cleveland Clinic Foundation) is a...
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10900 Euclid Ave
Cleveland, Ohio 44106
Cleveland, Ohio 44106
216-368-2000
Principal Investigator: David J. Adelstein
Phone: 866-223-8100
Case Western Reserve Univ Continually ranked among America's best colleges, Case Western Reserve University has...
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6001 E Woodmen Rd
Colorado Springs, Colorado 80923
Colorado Springs, Colorado 80923
(719) 776-5000
Principal Investigator: Keren Sturtz
Phone: 888-785-6789
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: Keren Sturtz
Phone: 888-785-6789
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Columbus, Ohio 43210
Principal Investigator: Enver Ozer
Phone: 800-293-5066
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Deerfield Beach, Florida 33442
Principal Investigator: Giovana R. Thomas
Phone: 866-574-5124
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2525 S Downing St
Denver, Colorado 80210
Denver, Colorado 80210
(303) 778-1955
Principal Investigator: Keren Sturtz
Phone: 888-785-6789
Porter Adventist Hospital Founded in 1930, Porter Adventist Hospital has provided people throughout Denver and...
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2799 W Grand Blvd
Detroit, Michigan 48202
Detroit, Michigan 48202
(313) 916-2600
Principal Investigator: Robert A. Chapman
Phone: 313-916-1784
Henry Ford Hospital Founded in 1915 by auto pioneer Henry Ford and now one of...
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2301 Erwin Rd
Durham, North Carolina 27710
Durham, North Carolina 27710
919-684-8111
Principal Investigator: Walter T. Lee
Phone: 888-275-3853
Duke Univ Med Ctr As a world-class academic and health care system, Duke Medicine strives...
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Hampton, Virginia 23666
Principal Investigator: Scott S. Williams
Phone: 757-388-2406
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Harrisburg, Pennsylvania 17109
Principal Investigator: Brij M. Sood
Phone: 717-724-6765
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Houston, Texas 77030
Principal Investigator: Michael E. Kupferman
Phone: 713-792-3245
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Iowa City, Iowa 52242
Principal Investigator: Daniel A. Vaena
Phone: 800-237-1225
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Kansas City, Kansas 66160
Principal Investigator: Yelizaveta Shnayder
Phone: 913-945-7552
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1 Medical Center Dr
Lebanon, New Hampshire 03756
Lebanon, New Hampshire 03756
(603) 650-5000
Principal Investigator: Thomas H. Davis
Phone: 800-639-6918
Dartmouth Hitchcock Medical Center Dartmouth-Hitchcock is a national leader in patient-centered health care and building...
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Lexington, Kentucky
Principal Investigator: Thomas J. Gal
Phone: 859-257-3379
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600 Highland Ave
Madison, Wisconsin 53792
Madison, Wisconsin 53792
(608) 263-6400
Principal Investigator: Paul M. Harari
Phone: 877-405-6866
University of Wisconsin Hospital and Clinics UW Health strives to meet the health needs of...
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Miami, Florida 33136
Principal Investigator: Giovana R. Thomas
Phone: 866-574-5124
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9200 W Wisconsin Ave
Milwaukee, Wisconsin 53226
Milwaukee, Wisconsin 53226
(414) 805-3666
Principal Investigator: Stuart J. Wong
Phone: 414-805-4380
Froedtert and the Medical College of Wisconsin Froedtert Health combines with the Medical College of...
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Milwaukee, Wisconsin 53295
Principal Investigator: Elizabeth M. Gore
Phone: 414-805-4380
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Nashville, Tennessee 37232
Principal Investigator: James L. Netterville
Phone: 800-811-8480
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New Haven, Connecticut 6520
(203) 432-4771
Principal Investigator: Benjamin L. Judson
Phone: 203-785-5702
Yale University Yale's roots can be traced back to the 1640s, when colonial clergymen led...
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1275 York Ave
New York, New York 10021
New York, New York 10021
(212) 639-2000
Principal Investigator: Luc G. Morris
Phone: 212-639-7202
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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Norfolk, Virginia 23507
Principal Investigator: Scott S. Williams
Phone: 757-388-2406
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Oakland, California 94611
Principal Investigator: Samantha A. Seaward
Phone: 626-564-3455
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Emile St
Omaha, Nebraska 68198
Omaha, Nebraska 68198
(402) 559-4000
Principal Investigator: Apar K. Ganti
Phone: 402-559-6941
Univ of Nebraska Med Ctr A vital enterprise in the nation’s heartland, the University of...
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8303 Dodge Street
Omaha, Nebraska 68114
Omaha, Nebraska 68114
(402) 354–4000
Principal Investigator: Russell B. Smith
Phone: 402-354-5144
Nebraska Methodist Hospital Methodist Hospital is a general medical and surgical hospital in Omaha, NE....
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Orlando, Florida 32803
Principal Investigator: Lee M. Zehngebot
Phone: 407-303-5623
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Philadelphia, Pennsylvania 19104
Principal Investigator: Gregory S. Weinstein
Phone: 800-474-9892
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Philadelphia, Pennsylvania 19111
Principal Investigator: Miriam N. Lango
Phone: 215-728-4790
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111 S 11th St
Philadelphia, Pennsylvania 19107
Philadelphia, Pennsylvania 19107
(215) 955-6000
Principal Investigator: David M. Cognetti
Phone: 215-955-6084
Thomas Jefferson University Hospital Our hospitals in Center City Philadelphia share a 13-acre campus with...
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Pittsburgh, Pennsylvania 15232
Principal Investigator: Robert L. Ferris
Phone: 412-647-8073
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San Francisco, California 94115
Principal Investigator: Sue S. Yom
Phone: 877-827-3222
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13400 E. Shea Blvd.
Scottsdale, Arizona 85259
Scottsdale, Arizona 85259
480-301-8000
Principal Investigator: Michael L. Hinni
Phone: 507-538-7623
Mayo Clinic Arizona Mayo Clinic in Arizona provides medical care for thousands of people from...
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1959 NE Pacific St
Seattle, Washington 98195
Seattle, Washington 98195
(206) 598-3300
Principal Investigator: Eduardo Mendez
Phone: 206-616-8289
University of Washington Medical Center University of Washington Medical Center is one of the nation's...
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1235 E Cherokee St
Springfield, Missouri 65804
Springfield, Missouri 65804
(417) 820-2000
Principal Investigator: Jay W. Carlson
Phone: 800-821-7532
Mercy Hospital Springfield We're continuing a tradition of healing more than 120 years old. Mercy...
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Virginia Beach, Virginia 23454
Principal Investigator: Scott S. Williams
Phone: 757-388-2406
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