Hormone Therapy, Radiation Therapy, and Steroid 17alpha-monooxygenase TAK-700 in Treating Patients With High-Risk Prostate Cancer

Phase 3

Active, not recruiting

Conditions: Prostate Cancer

Interventions: Drug: GnRH agonist
Drug: Anti-androgen
Drug: TAK-700
Radiation: Radiation therapy

Registration Number: NCT01546987

Lead Sponsor: Radiation Therapy Oncology Group

Brief Summary: RATIONALE: Androgens can cause the growth of prostate cancer cells. Drugs, such as steroid 17alpha-monooxygenase TAK-700, when used with other hormone therapy, may lessen the amount of androgens made by the body. Radiation therapy uses high energy x rays to kill tumor cells. This may be an effective treatment for prostate cancer when combined with hormone therapy. Studying quality-of-life in patients having cancer treatment may help identify the intermediate- and long-term effects of treatment on patients with prostate cancer.

PURPOSE: This randomized phase III trial is studying the use of hormone therapy, including TAK-700, together with radiation therapy in treating patients with prostate cancer.

Detailed Description: OBJECTIVES:

Primary

* To evaluate the difference in overall survival of patients with clinically localized prostate cancer with unfavorable prognostic features between a) standard treatment (androgen-deprivation therapy \[ADT\] + radiotherapy) and b) standard treatment with the addition of 24 months of steroid 17alpha-monooxygenase TAK-700 (TAK-700).

Secondary

* To characterize differences between the treatment groups with respect to incidence of unexpected grade ≥ 3 adverse events and/or clinically significant decrement in patient-reported quality of life (QOL) among subjects treated with TAK-700.

* To compare rates and cumulative incidence of biochemical control (freedom from PSA failure), local/regional progression, and distant metastases.

* To compare rate and cumulative incidence of clinical failure, defined as prostate-specific antigen (PSA) \> 25 ng/mL, documented local disease progression, regional or distant metastasis, or initiation of ADT.

* To compare prostate cancer-specific survival and other-cause mortality.

* To compare the change in severity of fatigue as measured by the Patient-Reported Outcome Measurement Information System (PROMIS) fatigue short form.

* To compare changes in patient-reported QOL as measured by Expanded Prostate Cancer Index Composite (EPIC).

* To assess quality-adjusted survival using the EQ-5D.

* To compare nadir and average serum testosterone at 12 and 24 months during treatment.

* To compare changes in hemoglobin A1C, fasting glucose, and fasting insulin during 24 months of systemic treatment and during the first three years of follow-up.

* To compare changes in fasting lipid levels during 24 months of treatment and during the first three years of follow-up.

* To compare changes in body mass index (BMI) during 24 months of treatment and during the first three years of follow-up.

* To compare the incidence of adverse events ascertained via CTCAE version 4.

* To compare the rate of recovery of testosterone to \> 230 ng/dL (accepted threshold for supplementation) after 12 and 24 months of follow-up.

* To compare the median time to recovery of testosterone to \> 230 ng/dL during the first five years of follow-up.

* To assess cumulative incidence of relevant clinical survivorship endpoints including new diagnosis of type 2 diabetes, coronary artery disease, myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis, or osteoporotic fracture.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to risk group (see Disease Characteristics) and type of radiation therapy (RT) boost (intensity-modulated RT (IMRT) vs brachytherapy). Patients are randomized to 1 of 2 treatment arms.

After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 1 year, and then annually thereafter.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: Male

Target Recruitment: 239

Inclusion Criteria

Histologically confirmed diagnosis of adenocarcinoma of the prostate within 180 days prior to registration at high risk for recurrence as determined by one of the following combinations:
- Gleason Score (GS) ≥ 9, PSA ≤ 150 ng/mL, any T stage
- GS ≥ 8, PSA < 20 ng/mL, T stage ≥ T2
- GS ≥ 8, PSA ≥ 20-150 ng/mL, any T stage
- GS ≥ 7, PSA ≥ 20-150 ng/mL, any T stage
History/physical examination within 60 days prior to registration.
Clinically negative lymph nodes as established by imaging [abdominal and/or pelvic computerized tomography (CT) or abdominal and/or pelvic magnetic resonance imaging (MRI)], nodal sampling, or dissection within 90 days prior to registration.

•Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are < 2.0 cm.
No distant metastases (M0) on bone scan within 90 days prior to registration (18F-Na bone scan is an acceptable substitute).

•Equivocal bone scan findings are allowed if plain films are negative for metastasis.
Baseline serum prostate-specific antigen (PSA) value performed with an FDA-approved assay (e.g., Abbott, Hybritech), obtained prior to any luteinizing hormone-releasing hormone (LHRH) or anti-androgen therapy, within 180 days of randomization.
Androgen deprivation therapy (ADT), such as LHRH agonists (e.g., goserelin, leuprolide), anti-androgens (e.g., flutamide, bicalutamide), estrogens (e.g., DES), or surgical castration (orchiectomy), may have been started prior to registration, provided that registration is within 50 days of beginning ADT. Please note: If the patient has started ADT he will not be eligible to participate in the quality of life component of this study.
Prior testosterone administration is allowed if last administered at least 90 days prior to registration.
Zubrod Performance Status 0-1 within 21 days prior to registration
Age ≥ 18
Complete blood count (CBC)/differential obtained within 14 days prior to registration on study, with adequate bone marrow function defined as follows:
- Absolute neutrophil count (ANC) ≥ 1,800 cells/mm3
- Platelets ≥ 100,000 cells/mm3
- Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
Serum creatinine < 2.0 mg/dl and creatinine clearance (can be calculated) > 40 mL/minute within 21 days prior to registration
Bilirubin < 1.5x upper limit of normal (ULN) and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5x ULN within 21 days prior to registration
Serum testosterone within 21 days prior to registration
Chemistry (including sodium, potassium, chloride, bicarbonate (carbon dioxide), blood urea nitrogen (BUN), glucose, calcium, magnesium and phosphorous) and liver panels (including albumin and alkaline phosphatase) obtained within 21 days prior to registration
Fasting glucose, fasting insulin, lipid panel [cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL)], and Hemoglobin A1C within 21 days prior to registration
Screening calculated ejection fraction of ≥ to institutional lower limit of normal by multiple gated acquisition (MUGA) scan or by echocardiogram (ECHO).
Baseline electrocardiogram (ECG) within 180 days prior to registration
Patients, even if surgically sterilized (ie, status post vasectomy), who:
1. Agree to practice effective barrier contraception during the entire study treatment period and for 4 months (120 days) after the last dose of study drug, or
2. Agree to completely abstain from intercourse.
Patient must be able to provide study-specific informed consent prior to study entry.

Exclusion Criteria

PSA > 150
Definite evidence of metastatic disease.
Pathologically positive lymph nodes or nodes > 2.0 cm on imaging.
Prior radical prostatectomy, cryosurgery for prostate cancer, or bilateral orchiectomy for any reason.
Prior invasive malignancy (except non-melanoma skin cancer) unless disease-free or not requiring systemic therapy for a minimum of 3 years.
Prior systemic chemotherapy for prostate cancer (Note that prior chemotherapy for a different cancer is allowed).
Prior radiotherapy, including brachytherapy, to the region of the prostate that would result in overlap of radiation therapy fields.

•Any patient undergoing brachytherapy must have transrectal ultrasound confirmation of prostate volume <60 cc, American Urological Association (AUA) score ≤15 within 60 days of registration, and no history of prior transurethral resection of the prostate (TURP); prior TURP is permitted for patients who receive external beam radiation therapy [EBRT] only).
Previous hormonal therapy for > 50 days.
Known hypersensitivity to TAK-700 or related compounds
A history of adrenal insufficiency
History of myocardial infarction, unstable symptomatic ischemic heart disease, ongoing arrhythmias of Grade > 2 [NCI CTCAE, version 4.02] (U.S. Department of Health and Human Services, National Institutes of Health National Cancer Institute, 2009), thromboembolic events (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), or any other cardiac condition (e.g., pericardial effusion restrictive cardiomyopathy) within 6 months prior to registration. Chronic stable atrial fibrillation on stable anticoagulant therapy is allowed.
New York Heart Association Class III or IV heart failure.
ECG abnormalities of:
1. Q-wave infarction, unless identified 6 or more months prior to screening
2. QTc interval > 460 msec
Patients who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
Prior allergic reaction to the drugs involved in this protocol.
Study entry PSA obtained during the following time frames:
1. 10-day period following prostate biopsy;
2. following initiation of hormonal therapy.
Cushing's syndrome
Severe chronic renal disease (serum creatinine > 2.0 mg/dl and confirmed by creatinine clearance < 40 mL/minute)
Chronic liver disease (bilirubin > 1.5x ULN, ALT or AST > 2.5x ULN)
Chronic treatment with glucocorticoids within one year
Uncontrolled hypertension despite appropriate medical therapy within 21 days prior to registration (blood pressure of greater than 150 mm Hg systolic and 90 mm Hg diastolic at 2 separate measurements no more than 60 minutes apart during Screening visit)
Unwilling or unable to comply with the protocol or cooperate fully with the investigator and site personnel.
Major surgery within 14 days prior to registration
Serious infection within 14 days prior to registration
Uncontrolled nausea, vomiting, or diarrhea [Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3] despite appropriate medical therapy at the time of registration
Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-700, including difficulty swallowing tablets

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ADT + RT	GnRH agonist	Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.
TAK-700 + ADT + RT	GnRH agonist	TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
TAK-700 + ADT + RT	Radiation therapy	TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
ADT + RT	Anti-androgen	Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.
ADT + RT	Radiation therapy	Standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT.
TAK-700 + ADT + RT	Anti-androgen	TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.
TAK-700 + ADT + RT	TAK-700	TAK-700 and standard androgen deprivation therapy (ADT) beginning two months prior to radiation therapy (RT). ADT comprised of anti-androgen continuing for two years and GnRH agonist stopping at end of RT. TAK-700 continues for two years.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Biochemical Failure (Primary Endpoint of Revised Protocol)	From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.	Note, the revised protocol (see Limitations and Caveats) changed this outcome measure from secondary (original protocol) to primary. Biochemical failure will be defined by the Phoenix definition (PSA ≥ 2 ng/ml over the nadir PSA, the presence of local, regional, or distant recurrence, or the initiation of salvage androgen deprivation therapy. Time to failure is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here.

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients Alive [Overall Survival] (Primary Endpoint of Original Protocol)	From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.	Note, the revised protocol (see Limitations and Caveats) changed this outcome measure from primary (original protocol) to secondary. Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. 5-year rates are provided.
Serum Testosterone	Baseline,12 months, 24 months
Fasting Total Cholesterol	Baseline, 12 months, 24 months
Fasting Plasma Glucose	Baseline, 12 months, 24 months
Fasting Plasma Insulin	Baseline, 12 months, 24 months
Percentage of Participants With Grade 3 or Higher Adverse Events	From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.	Time to grade 3 or higher adverse event (event) is defined as time from randomization to the date of first event, last known follow-up (censored), or death without failure (competing risk). Event rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here.
Change in Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form at One Year	Baseline, one year	The PROMIS Fatigue short form 8a contains 8 questions, each with 5 responses ranging from 1 to 5, evaluating self-reported fatigue symptoms over the past 7 days. The total score is the sum of all questions which is then converted into a pro-rated T-score with a mean of 50 and standard deviation of 10, with a possible range of 33.1 to 77.8. Higher scores indicate more fatigue. Change is defined as value at one year - value at baseline. Positive change from baseline indicates increased fatigue at one year.
Serum High-density Lipoprotein (HDL)	Baseline, 12 months, 24 months
Change From Baseline in Body Mass Index (BMI)	Baseline and yearly to five years.	Body Mass Index (BMI) is a person's weight in kilograms (or pounds) divided by the square of height in meters (or feet). Change from baseline = time point value - baseline value.
Percentage of Participants With Local Progression	From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates reported.	Local recurrence (failure) is defined as biopsy proven recurrence within the prostate gland. Time to failure is defined as time from randomization to the date of failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here.
Percentage of Participants With Distant Metastases	From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.	Distant metastases (failure) is defined as imaging or biopsy demonstrated evidence for systemic recurrence. Biopsy was not required, however it was encouraged in absence of a rising PSA. Time to failure is defined as time from randomization to the date of first failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here. Note, the protocol lists this endpoint as regional or distant metastasis, but regional progression data was not collected.
Percentage of Participants With General Clinical Treatment Failure	From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.	General clinical treatment failure (GCTF) is defined as: PSA \> 25 ng/ml, documented local disease progression, regional or distant metastasis, or initiation of salvage androgen deprivation therapy. Failure time is defined as time from registration to the date of failure, last known follow-up (censored), or death without failure (competing risk). Failure rates are estimated using the cumulative incidence method, while treatment effect comparisons are based on cause-specific hazards (deaths censored). Five-year rates are provided here.
Percentage of Participants With Death Due to Prostate Cancer	From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.	Time to prostate cancer death is defined as time from randomization to the date of death due to prostate cancer, last known follow-up (censored), or death due to other causes (competing risk). Failure rates were to be estimated using the cumulative incidence method. If too few events occur for meaningful estimates, then only counts of events will be reported.
Number of Patients With Clinical Survivorship Events	From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.	Clinical survivorship events are defined as the following newly diagnosed non-fatal cardiovascular events or other clinical endpoints relevant to prostate cancer survivorship: type 2 diabetes, coronary artery disease, myocardial infarction, stroke, pulmonary embolism, deep vein thrombosis, and osteoporotic fracture.
Change in Patient-reported Quality of Life as Measured by Expanded Prostate Cancer Index Composite (EPIC) Short Form at One Year	Baseline, one year	The EPIC-Short Form is a 26-item, validated self-administered tool to assess disease-specific aspects of prostate cancer and its therapies consisting of five summary domains (bowel, urinary incontinence, urinary irritation/obstruction, sexual, and hormonal function). Responses for each item form a Likert scale which are transformed to a 0-100 scale. A domain score is the average of the transformed domain item scores, ranging from 0-100 with higher scores representing better health-related quality of life (HRQOL). Change at one year is defined as one-year value - baseline value. Positive change at one year indicates improved quality of life.
Serum High-density Lipoprotein (LDL)	Baseline, 12 months, 24 months
Hemoglobin A1c	Baseline, 12 months, 24 months
Number of Participants by Highest Grade Adverse Event	From registration to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.	Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data
Testosterone Recovery at 12 and 24 Months	From registration to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years.	Testosterone recovery is defined as testosterone level after treatment greater than 230 ng/dL. Time to testosterone recovery is defined as time from randomization to the date of testosterone recovery, biochemical, local, or distant failure (competing risk), salvage therapy (competing risk), death (competing risk), or last known follow-up (censored). Testosterone recovery rates are estimated using the cumulative incidence method.
Median Testosterone Recovery Time	From randomization to last follow-up. Follow-up schedule: every 3 months from start of treatment for 2 years, then every 6 months for 3 years, then yearly. Maximum follow-up at time of analysis was 9.1 years. Five-year rates are reported here.	Testosterone recovery is defined as testosterone level after treatment greater than 230 ng/dL. Testosterone recovery rates are estimated using the Kaplan-Meier method, censoring for biochemical, local, or distant failure, salvage therapy, death, and otherwise alive without event. Testosterone recovery time is defined as time from randomization to testosterone recovery or censoring.

Trial Locations

Locations (172): Ohio State University Medical Center
🇺🇸
Columbus, Ohio, United States
Case Western Reserve University
🇺🇸
Cleveland, Ohio, United States
Saint John's Mercy Medical Center
🇺🇸
Saint Louis, Missouri, United States
Ochsner Medical Center Jefferson
🇺🇸
New Orleans, Louisiana, United States
Dana-Farber/Brigham and Women's Cancer Center at Milford Regional
🇺🇸
Milford, Massachusetts, United States
Kansas City Cancer Centers - North
🇺🇸
Kansas City, Missouri, United States
Peninsula Regional Medical Center
🇺🇸
Salisbury, Maryland, United States
OSF Saint Francis Medical Center
🇺🇸
Peoria, Illinois, United States
Saint Luke's Hospital of Duluth
🇺🇸
Duluth, Minnesota, United States
Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
Dana-Farber/Brigham and Women's Cancer Center at South Shore
🇺🇸
South Weymouth, Massachusetts, United States
Mary Bird Perkins Cancer Center
🇺🇸
Baton Rouge, Louisiana, United States
Radiation Oncology Associates PC
🇺🇸
Fort Wayne, Indiana, United States
McLaren-Flint
🇺🇸
Flint, Michigan, United States
Maine Medical Center- Scarborough Campus
🇺🇸
Scarborough, Maine, United States
Saint Agnes Hospital
🇺🇸
Baltimore, Maryland, United States
University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
Kansas City Cancer Center - South
🇺🇸
Kansas City, Missouri, United States
Saint Anne's Hospital
🇺🇸
Fall River, Massachusetts, United States
Northern Michigan Regional Hospital
🇺🇸
Petoskey, Michigan, United States
Kansas City Cancer Center-Lee's Summit
🇺🇸
Lee's Summit, Missouri, United States
Sanford Bismarck Medical Center
🇺🇸
Bismarck, North Dakota, United States
Decatur Memorial Hospital
🇺🇸
Decatur, Illinois, United States
Lake University Ireland Cancer Center
🇺🇸
Mentor, Ohio, United States
Massachusetts General Hospital Cancer Center
🇺🇸
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Regions Hospital
🇺🇸
Saint Paul, Minnesota, United States
Hines Veterans Administration Hospital
🇺🇸
Hines, Illinois, United States
Exeter Hospital
🇺🇸
Exeter, New Hampshire, United States
Siteman Cancer Center-South County
🇺🇸
Saint Louis, Missouri, United States
Cleveland Clinic Foundation
🇺🇸
Cleveland, Ohio, United States
Parkview Hospital Randallia
🇺🇸
Fort Wayne, Indiana, United States
University of Kentucky
🇺🇸
Lexington, Kentucky, United States
Touro Infirmary
🇺🇸
New Orleans, Louisiana, United States
North Shore Medical Center Cancer Center
🇺🇸
Peabody, Massachusetts, United States
Concord Hospital
🇺🇸
Concord, New Hampshire, United States
UTMB Cancer Center at Victory Lakes
🇺🇸
League City, Texas, United States
West Michigan Cancer Center
🇺🇸
Kalamazoo, Michigan, United States
William Beaumont Hospital-Royal Oak
🇺🇸
Royal Oak, Michigan, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Saint Vincent Hospital
🇺🇸
Green Bay, Wisconsin, United States
Summa Akron City Hospital/Cooper Cancer Center
🇺🇸
Akron, Ohio, United States
MD Anderson Cancer Center at Cooper-Voorhees
🇺🇸
Voorhees, New Jersey, United States
Elliot Hospital
🇺🇸
Manchester, New Hampshire, United States
Sentara Hospitals
🇺🇸
Norfolk, Virginia, United States
Southeast Cancer Center
🇺🇸
Cape Girardeau, Missouri, United States
UHHS-Chagrin Highlands Medical Center
🇺🇸
Orange Village, Ohio, United States
Lankenau Hospital
🇺🇸
Wynnewood, Pennsylvania, United States
Appleton Medical Center
🇺🇸
Appleton, Wisconsin, United States
CHUM - Hopital Notre-Dame
🇨🇦
Montreal, Quebec, Canada
Saint Peter's University Hospital
🇺🇸
New Brunswick, New Jersey, United States
Cooper Hospital University Medical Center
🇺🇸
Camden, New Jersey, United States
Rogue Valley Medical Center
🇺🇸
Medford, Oregon, United States
Texas Cancer Center-Sherman
🇺🇸
Sherman, Texas, United States
Bay Area Medical Center
🇺🇸
Marinette, Wisconsin, United States
Geaugra Hospital
🇺🇸
Chardon, Ohio, United States
Southwest General Health Center Ireland Cancer Center
🇺🇸
Middleburg Heights, Ohio, United States
Summa Barberton Hospital
🇺🇸
Barberton, Ohio, United States
Saskatoon Cancer Centre
🇨🇦
Saskatoon, Saskatchewan, Canada
Mercy Cancer Center-Elyria
🇺🇸
Elyria, Ohio, United States
Texas Oncology PA - Bedford
🇺🇸
Bedford, Texas, United States
Robinson Radiation Oncology
🇺🇸
Ravenna, Ohio, United States
Akron General Medical Center
🇺🇸
Akron, Ohio, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
Rapid City Regional Hospital
🇺🇸
Rapid City, South Dakota, United States
Intermountain Medical Center
🇺🇸
Murray, Utah, United States
Oncology and Hematology Associates of Southwest Virginia
🇺🇸
Roanoke, Virginia, United States
Adams Cancer Center
🇺🇸
Gettysburg, Pennsylvania, United States
Tom Baker Cancer Centre
🇨🇦
Calgary, Alberta, Canada
Gundersen Lutheran
🇺🇸
La Crosse, Wisconsin, United States
London Regional Cancer Program
🇨🇦
London, Ontario, Canada
Door County Cancer Center
🇺🇸
Sturgeon Bay, Wisconsin, United States
Wheaton Franciscan Cancer Care - All Saints
🇺🇸
Racine, Wisconsin, United States
Saint Mary's Hospital
🇺🇸
Green Bay, Wisconsin, United States
Allan Blair Cancer Centre
🇨🇦
Regina, Saskatchewan, Canada
Virginia Mason CCOP
🇺🇸
Seattle, Washington, United States
Memorial Hermann Memorial City Medical Center
🇺🇸
Houston, Texas, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
University of California At San Diego
🇺🇸
San Diego, California, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
UCSF-Mount Zion
🇺🇸
San Francisco, California, United States
Utah Cancer Specialists-Salt Lake City
🇺🇸
Salt Lake City, Utah, United States
Kansas City Cancer Centers-Southwest
🇺🇸
Overland Park, Kansas, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Arizona Oncology Services Foundation
🇺🇸
Scottsdale, Arizona, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
🇺🇸
Auburn, California, United States
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
🇺🇸
Cameron Park, California, United States
Mercy San Juan Medical Center
🇺🇸
Carmichael, California, United States
Veterans Administration Long Beach Medical Center
🇺🇸
Long Beach, California, United States
Los Angeles County-USC Medical Center
🇺🇸
Los Angeles, California, United States
University of Southern California/Norris Cancer Center
🇺🇸
Los Angeles, California, United States
Pomona Valley Hospital Medical Center
🇺🇸
Pomona, California, United States
Rohnert Park Cancer Center
🇺🇸
Rohnert Park, California, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
🇺🇸
Roseville, California, United States
Kaiser Permanente Cancer Treatment Center
🇺🇸
South San Francisco, California, United States
Stanford University Hospitals and Clinics
🇺🇸
Stanford, California, United States
Sutter Solano Medical Center
🇺🇸
Vallejo, California, United States
Sutter Cancer Centers Radiation Oncology Services-Vacaville
🇺🇸
Vacaville, California, United States
Poudre Valley Radiation Oncology
🇺🇸
Fort Collins, Colorado, United States
The Hospital of Central Connecticut
🇺🇸
New Britain, Connecticut, United States
Hartford Hospital
🇺🇸
Hartford, Connecticut, United States
William Backus Hospital
🇺🇸
Norwich, Connecticut, United States
Helen F Graham Cancer Center
🇺🇸
Newark, Delaware, United States
Christiana Care Health System-Christiana Hospital
🇺🇸
Newark, Delaware, United States
University of Miami Sylvester Comprehensive Cancer Center at Deerfield Beach
🇺🇸
Deerfield Beach, Florida, United States
Florida Hospital
🇺🇸
Orlando, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸
Miami, Florida, United States
Grady Health System
🇺🇸
Atlanta, Georgia, United States
Piedmont Hospital
🇺🇸
Atlanta, Georgia, United States
Emory University/Winship Cancer Institute
🇺🇸
Atlanta, Georgia, United States
Atlanta VA Medical Center
🇺🇸
Decatur, Georgia, United States
Saint Joseph's-Candler Health System
🇺🇸
Savannah, Georgia, United States
Queen's Medical Center
🇺🇸
Honolulu, Hawaii, United States
Saint Alphonsus Regional Medical Center
🇺🇸
Boise, Idaho, United States
Weiss Memorial Hospital
🇺🇸
Chicago, Illinois, United States
Idaho Urologic Institute PA
🇺🇸
Meridian, Idaho, United States
Arizona Oncology-Deer Valley Center
🇺🇸
Phoenix, Arizona, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Nebraska Methodist Hospital
🇺🇸
Omaha, Nebraska, United States
The Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Columbia Saint Mary's Water Tower Medical Commons
🇺🇸
Milwaukee, Wisconsin, United States
Froedtert and the Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
Clement J. Zablocki VA Medical Center
🇺🇸
Milwaukee, Wisconsin, United States
The Kirklin Clinic at Acton Road
🇺🇸
Birmingham, Alabama, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Barnes-Jewish West County Hospital
🇺🇸
Saint Louis, Missouri, United States
Siteman Cancer Center - Saint Peters
🇺🇸
Saint Peters, Missouri, United States
Mercy Hospital Springfield
🇺🇸
Springfield, Missouri, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
William Beaumont Hospital - Troy
🇺🇸
Troy, Michigan, United States
Temple University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
Great Lakes Cancer Institute-Lapeer Campus
🇺🇸
Lapeer, Michigan, United States
Sanford Clinic North-Bemidgi
🇺🇸
Bemidji, Minnesota, United States
Cedars-Sinai Medical Center
🇺🇸
Los Angeles, California, United States
McLaren Cancer Institute-Owosso
🇺🇸
Owosso, Michigan, United States
The Regional Cancer Center
🇺🇸
Erie, Pennsylvania, United States
Paoli Memorial Hospital
🇺🇸
Paoli, Pennsylvania, United States
Cherry Tree Cancer Center
🇺🇸
Hanover, Pennsylvania, United States
Missouri Baptist Medical Center
🇺🇸
Saint Louis, Missouri, United States
Dartmouth Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
Thomas Jefferson University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
Reading Hospital
🇺🇸
West Reading, Pennsylvania, United States
Summa Health Center at Lake Medina
🇺🇸
Medina, Ohio, United States
Natalie Warren Bryant Cancer Center at Saint Francis
🇺🇸
Tulsa, Oklahoma, United States
WellSpan Health-York Hospital
🇺🇸
York, Pennsylvania, United States
Flower Hospital
🇺🇸
Sylvania, Ohio, United States
University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
Delaware County Memorial Hospital
🇺🇸
Drexel Hill, Pennsylvania, United States
Gibbs Cancer Center-Pelham
🇺🇸
Greer, South Carolina, United States
Spartanburg Regional Medical Center
🇺🇸
Spartanburg, South Carolina, United States
Columbia Saint Mary's Hospital - Ozaukee
🇺🇸
Mequon, Wisconsin, United States
Lexington Medical Center
🇺🇸
West Columbia, South Carolina, United States
Sentara Virginia Beach General Hospital
🇺🇸
Virginia Beach, Virginia, United States
The Klabzuba Cancer Center
🇺🇸
Fort Worth, Texas, United States
University of Texas Medical Branch at Galveston
🇺🇸
Galveston, Texas, United States
Texas Oncology Cancer Center Sugar Land
🇺🇸
Sugar Land, Texas, United States
Dixie Medical Center Regional Cancer Center
🇺🇸
Saint George, Utah, United States
Sentara Cancer Institute at Sentara CarePlex Hospital
🇺🇸
Hampton, Virginia, United States
Saint Francis Hospital
🇺🇸
Federal Way, Washington, United States
Ottawa Health Research Institute-General Division
🇨🇦
Ottawa, Ontario, Canada
Sutter General Hospital
🇺🇸
Sacramento, California, United States
University of Colorado Cancer Center - Anschutz Cancer Pavilion
🇺🇸
Aurora, Colorado, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Saint Joseph Mercy Hospital
🇺🇸
Ann Arbor, Michigan, United States
Benefis Healthcare- Sletten Cancer Institute
🇺🇸
Great Falls, Montana, United States
BCCA-Cancer Centre for the Southern Interior
🇨🇦
Kelowna, British Columbia, Canada
Sanford Medical Center-Fargo
🇺🇸
Fargo, North Dakota, United States
Ireland Cancer Center at Firelands Regional Medical Center
🇺🇸
Sandusky, Ohio, United States
UHHS-Westlake Medical Center
🇺🇸
Westlake, Ohio, United States
Kaiser Permanente Medical Center - Santa Clara
🇺🇸
Santa Clara, California, United States
Bixby Medical Center
🇺🇸
Adrian, Michigan, United States
University of Kansas Medical Center
🇺🇸
Kansas City, Kansas, United States