Bladder Cancer Clinical Trial
A Study of Chemotherapy and Radiation Therapy Compared to Chemotherapy and Radiation Therapy Plus MEDI4736 (Durvalumab) Immunotherapy for Bladder Cancer Which Has Spread to the Lymph Nodes (The INSPIRE Study)
Summary
This phase II trial studies the benefit of adding an immunotherapy drug called MEDI4736 (durvalumab) to standard chemotherapy and radiation therapy in treating bladder cancer which has spread to the lymph nodes. Drugs used in standard chemotherapy 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. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Immunotherapy with durvalumab may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving chemotherapy and radiation therapy with the addition of durvalumab may work better in helping tumors respond to treatment compared to chemotherapy and radiation therapy alone. Patients with limited regional lymph node involvement may benefit from attempt at bladder preservation, and use of immunotherapy and systemic chemotherapy.
Full Description
PRIMARY OBJECTIVE:
I. To compare the clinical complete response rate (cCR) after chemoradiotherapy (chemoRT) with or without durvalumab in node-positive bladder cancer patients.
SECONDARY OBJECTIVES:
I. To compare the toxicity profile in both arms using the Common Terminology Criteria for Adverse Events (CTCAE).
II. To estimate the progression-free survival (PFS) in both arms. III. To estimate overall survival (OS) post randomization in both arms. IV. To estimate the bladder intact event free survival (BIEFS) in both arms. V. To estimate the metastasis free survival (MFS) in both arms. VI. To estimate bladder cancer specific survival in both arms. VII. To estimate the complete clinical response duration in both arms. VIII. To estimate salvage cystectomy rates in both arms.
EXPLORATORY OBJECTIVE:
I. Planned subgroup analyses for clinical outcome (clinical complete response [CR] rate post chemoRT +/- durvalumab, MFS, OS, PFS) based on stratification factors.
TRANSLATIONAL OBJECTIVE:
I. To collect and bank tumor tissue and blood specimens at pre-and post-treatment with chemoRT +/- durvalumab to determine predictive or prognostic markers.
OUTLINE:
STEP 1 - Randomization: Patients are randomized to 1 of 2 arms.
ARM C: Patients undergo radiation therapy for 6.5-8 weeks. Beginning 4 days before or after starting radiation therapy, patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning 4 days before or after starting radiation therapy, patients also receive gemcitabine hydrochloride IV over 30-60 minutes twice a week (BIW) for 6 weeks; cisplatin IV over 30-60 minutes once a week (QW) for 6 weeks; or mitomycin IV over 30 minutes on day 1 of radiation and fluorouracil IV continuous infusion on days 1-5 and 16-20 of radiation in the absence of disease progression or unacceptable toxicity. Patients also undergo bladder biopsy, cystoscopy, and computed tomography (CT) or magnetic resonance imaging (MRI) on study. Patients may also undergo tumor tissue and blood sample collection on study.
ARM D: Patients undergo radiation therapy for 6.5-8 weeks. Beginning 4 days before or after starting radiation therapy, patients also receive gemcitabine hydrochloride IV over 30-60 minutes BIW for 6 weeks; cisplatin IV over 30-60 minutes QW for 6 weeks; or mitomycin IV over 30 minutes on day 1 of radiation and fluorouracil IV continuous infusion on days 1-5 and 16-20 of radiation in the absence of disease progression or unacceptable toxicity. Patients also undergo bladder biopsy, cystoscopy, and CT or MRI on study. Patients may also undergo tumor tissue and blood sample collection on study.
STEP 2 - Registration: Patients are assigned to 1 of 2 arms.
ARM E: Patients previously randomized to Arm C (chemoradiation and durvalumab) who achieve clinical CR or clinical benefit receive durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bladder biopsy, cystoscopy, and CT or MRI on study. Patients may also undergo tumor tissue and blood sample collection on study.
ARM F: Patients previously randomized to Arm D (chemoradiation) who achieve clinical CR or clinical benefit, or patients previously randomized to Arm C with no clinical CR or clinical benefit undergo observation. Patients also undergo bladder biopsy, cystoscopy, and CT or MRI on study. Patients may also undergo tumor tissue and blood sample collection on study.
After completion of study treatment, patients are followed up every 12 weeks for 1 year, every 6 months for year 2, and then annually for years 3-4.
Eligibility Criteria
Inclusion Criteria:
Step 1 (Randomization) Inclusion
Patient must be >= 18 years of age
Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of step 1 randomization
Patient must have histologically proven pure or mixed urothelial cancer of the bladder
NOTE: Small cell carcinoma is excluded, however other variant histologies are permitted provided a component of urothelial carcinoma is present
Patient must have documented node-positive and non-metastatic disease (any T, any N, M0). Node positivity must have been defined prior to receiving and systemic chemotherapy or induction chemotherapy.
Node positivity can fall into either of the following categories and will be defined by imaging and/or biopsy:
A lymph node >= 1.0 cm in short axis on imaging (i.e., CT or MRI or positron emission tomography [PET]/CT)
A lymph node that is < 1 cm on imaging with either a biopsy confirming involvement with cancer
For patients who have received induction chemotherapy (any type of systemic chemotherapy) for node positive bladder cancer prior to enrollment, there must be no signs of disease progression (CR/PR or stable disease [SD]) based on restaging imaging and cystoscopy, which consists of:
CT chest, abdomen, and pelvis obtained after completion of induction chemotherapy and within 8 weeks prior to step 1 randomization
NOTE: MRI can be used instead of CT per treating physician discretion
Cystoscopic evaluation and attempt to perform maximal TURBT performed by the participating urologist after completion of induction chemotherapy and within 12 weeks prior to step 1 randomization. If maximal TURBT is not possible for medical reasons, the enrollment must be discussed and approved with the study chair. Documentation of correspondences with the study chair must be kept on file
Patients who achieve CR upon cystoscopy per urologist with no visible tumor (i.e., no need for additional TURBT), are allowed to proceed in the study as adequate resection with no residual disease in bladder
For patients who did not receive induction chemotherapy (any type of systemic chemotherapy) for node positive bladder cancer prior to enrollment, the following must be obtained:
CT chest, abdomen, and pelvis completed within 8 weeks prior to step 1 randomization.
NOTE: MRI can be used instead of CT per treating physician discretion
Cystoscopic evaluation and attempt to perform maximal TURBT performed by the participating urologist within 12 weeks prior to Step 1 randomization. If maximal TURBT is not possible for medical reasons, the enrollment must be discussed and approved with the study chair. Documentation of correspondences with the study chair must be kept on file.
For patients who may need repeat TURBT if their old TURBT has fallen out of window: If urologist determine no visible tumor (i.e., no need for additional resection) upon cystoscopy, they are allowed to proceed in the study as complete resection
Patient must agree to undergo CT simulation and treatment planning. If this is the first case registered at the site, then a pre-treatment RT review will be required and will take up to 3 business days. The patient cannot start radiation treatment prior to successful completion of this pre-treatment review. Therefore, careful planning is necessary to meet the deadline of starting radiation within 20 business days of Step 1 randomization
Patients with previous exposure to immune checkpoint inhibitor for non-muscle invasive disease are eligible. If given for NMIBC, the last dose must have been completed > 12 months prior to step 1 randomization
Leukocytes >= 3,000/mcL (obtained < 14 days prior to step 1 randomization)
Absolute neutrophil count (ANC) >= 1,500/mcL (obtained < 14 days prior to step 1 randomization)
Hemoglobin >= 9 g/dL (obtained < 14 days prior to step 1 randomization)
Platelets >= 100,000/mcL (obtained < 14 days prior to step 1 randomization)
Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (obtained < 14 days prior to step 1 randomization)
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained < 14 days prior to step 1 randomization)
Adequate renal function as evidenced by calculated (Cockcroft's formula) creatinine clearance or 24 hours actual creatinine clearance >= 30mL/min. The creatinine used to calculate the clearance result must have been obtained within 14 days prior to step 1 randomization. Actual body weight, not ideal body weight, must be used in the calculation
Patients with human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months of step 1 randomization are eligible for this trial
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Site is encouraged to discuss with the study chair if needed prior to enrollment
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 trial, patients should be class IIB or better
Step 2 (Registration: Adjuvant Durvalumab vs. Observation) Inclusion
Patient must have evaluation to determine clinical outcome post step 1 treatment (chemoRT+/- durvalumab) with imaging (CT chest, abdomen, and pelvis)(preferably contrast with urogram, if not contraindicated) and cystoscopy with biopsy confirmation to ensure no progression and absence of >= T2 disease in the bladder. Patient should be registered to step 2 within 28 days from the determination of primary response to step 1 treatment. However, for patients previously on Arm C, an additional 4 week delay to step 2 registration is allowed
Patient on the chemoRT+ durvalumab (Arm C) must meet the following:
Patient must have achieved either complete clinical response OR have demonstrated clinical benefit prior to continuing onto adjuvant durvalumab
Patients who are to go on the adjuvant durvalumab (Arm E) must have recovered to at least grade 2 or less immune related AE prior to starting treatment except for immune related alopecia, clinically asymptomatic endocrinopathies. For patients who may have gotten immune related AEs during chemoRT+ durvalumab (Arm C), step 2 registration could be delayed up to additional 4 weeks to ensure recovery to at least grade 2 or lower prior to starting adjuvant therapy. However patients with durvalumab related AEs that require permanent discontinuation of durvalumab will not continue on the adjuvant treatment regardless of the response
Patient must not have experienced immune related neurological disorder described as Guillain-Barré syndrome, myasthenic syndrome or myasthenia gravis, or meningoencephalitis during chemoRT+ durvalumab treatment
Patient must not have experienced immune related myocarditis or immune related pericarditis during chemoRT+ durvalumab treatment
ANC >= 1,000 mcL (must be obtained < 28 days prior to step 2 registration)
Hemoglobin >= 8g/dL (must be obtained < 28 days prior to step 2 registration)
Platelets >= 70,000 mcL (must be obtained < 28 days prior to step 2 registration)
NOTE: If recovery is not achieved, blood counts could be repeated weekly and step 2 registration could be delayed up to additional 4 weeks
Patient on the chemoRT arm (Arm D) must have achieved either complete clinical response OR have demonstrated clinical benefit prior to be placed on the observation alone arm (Arm F)
Exclusion Criteria:
Step 1 (Randomization) Exclusion
Patient must not have received any previous radiation therapy to the pelvic area
Patient must not have presence of concomitant active upper tract tumors or urethra tumors. History of previously adequately treated non-muscle invasive bladder cancer (NMIBC) are eligible; previously treated urothelial cancer or histological variant at any site outside of the urinary bladder are allowed, provided they have been Ta/T1/carcinoma in situ (CIS) and post treatment follow up imaging and endoscopic evaluation shows no evidence of disease
Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.
All patients of childbearing potential must have a blood test or urine study within 14 days prior to step 1 randomization to rule out pregnancy.
A patient of childbearing potential is defined as any patient, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
Patients must not expect to conceive or father children by using accepted and effected method(s) of contraception or by abstaining from sexual intercourse from the time of Step 1 randomization for the duration of their participation in the study and continue for at least 3 months after the last dose of protocol treatment
For patients with autoimmune conditions, patient must not have history of prior documented autoimmune disease within 2 years prior to step 1 randomization
NOTE: Patient with vitiligo, Grave's disease, eczema or psoriasis (not requiring systemic treatment within 2 years prior to step 1 randomization) are not excluded. Patients with history of completely resolved childhood asthma or atopy are not excluded. Patients with asthma not requiring more than 10 mg/d or equivalent of prednisone are not excluded. Patients with well-controlled hypothyroidism on thyroxine replacement will be eligible as well. Patients with known history of hypoadrenalism on maintenance steroids will be eligible. Patients with type I diabetes mellitus will be eligible, provided their disease is well controlled. History of autoimmune related alopecia is also not an exclusion criteria
Patient with active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) are not eligible
Patient with a history of and/or confirmed pneumonitis are not eligible
Patient with a history of primary immunodeficiency are not eligible
Patient with history of allogeneic organ transplant are not eligible
Patient must not have an active infection, including:
Tuberculosis (based on clinical evaluation that includes clinical history, physical examination, and radiographic findings, and tuberculosis testing in line with local practice)
Hepatitis B (HBV) (known positive HBV surface antigen [HBsAg] result). Past or resolved HBV infection (defined as the presence of hepatitis b core antibody [anti-HBc] and absence of HBsAg) are eligible
Hepatitis C Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction test is negative for HCV ribonucleic acid (RNA)
Patient must not have clinically significant liver disease that precludes patient from treatment regimens prescribed on the study (including, but not limited to, active viral, alcoholic or other autoimmune hepatitis, cirrhosis or inherited liver disease)
Patient must not have received live attenuated vaccine within 30 days prior to the first dose of durvalumab
NOTE: Patient, if enrolled, must not receive live vaccine whilst receiving durvalumab and up to 30 days after the last dose of durvalumab
NOTE: Patient is permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and COVID-19 (Note: intranasal influenza vaccines, such as Flu-Mist are live attenuated vaccines and are not allowed). If possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily in order to minimize an overlap of adverse events)
Patient must not have current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection).
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
Patient must not have any unresolved toxicity (National Cancer Institute [NCI] CTCAE grade >= 2) from previous anti-cancer therapy with the exception of alopecia, vitiligo, and the laboratory values
NOTE: Patients with grade >= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study chair
NOTE: Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the study chair. Documentation of correspondences with the study chair must be kept on file
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There are 182 Locations for this study
Anchorage Alaska, 98508, United States
Anchorage Alaska, 99508, United States
Anchorage Alaska, 99508, United States
Anchorage Alaska, 99508, United States
Anchorage Alaska, 99508, United States
Anchorage Alaska, 99508, United States
Anchorage Alaska, 99508, United States
Fort Smith Arkansas, 72903, United States
Hot Springs Arkansas, 71913, United States
Burbank California, 91505, United States
Palo Alto California, 94304, United States
Colorado Springs Colorado, 80907, United States
Colorado Springs Colorado, 80907, United States
Denver Colorado, 80210, United States
Lakewood Colorado, 80228, United States
Littleton Colorado, 80122, United States
Longmont Colorado, 80501, United States
Parker Colorado, 80138, United States
Pueblo Colorado, 81004, United States
Frankford Delaware, 19945, United States
Newark Delaware, 19713, United States
Newark Delaware, 19713, United States
Rehoboth Beach Delaware, 19971, United States
Washington District of Columbia, 20016, United States
Fort Lauderdale Florida, 33308, United States
Miami Beach Florida, 33140, United States
Atlanta Georgia, 30308, United States
Atlanta Georgia, 30322, United States
Boise Idaho, 83706, United States
Boise Idaho, 83712, United States
Caldwell Idaho, 83605, United States
Coeur d'Alene Idaho, 83814, United States
Fruitland Idaho, 83619, United States
Meridian Idaho, 83642, United States
Meridian Idaho, 83642, United States
Nampa Idaho, 83686, United States
Nampa Idaho, 83687, United States
Post Falls Idaho, 83854, United States
Twin Falls Idaho, 83301, United States
Aurora Illinois, 60504, United States
Bloomington Illinois, 61704, United States
Canton Illinois, 61520, United States
Carbondale Illinois, 62902, United States
Carterville Illinois, 62918, United States
Carthage Illinois, 62321, United States
Centralia Illinois, 62801, United States
Chicago Illinois, 60611, United States
Danville Illinois, 61832, United States
Decatur Illinois, 62526, United States
Decatur Illinois, 62526, United States
DeKalb Illinois, 60115, United States
Effingham Illinois, 62401, United States
Effingham Illinois, 62401, United States
Eureka Illinois, 61530, United States
Galesburg Illinois, 61401, United States
Galesburg Illinois, 61401, United States
Geneva Illinois, 60134, United States
Hines Illinois, 60141, United States
Kewanee Illinois, 61443, United States
Lake Forest Illinois, 60045, United States
Macomb Illinois, 61455, United States
Mattoon Illinois, 61938, United States
Maywood Illinois, 60153, United States
Mount Vernon Illinois, 62864, United States
O'Fallon Illinois, 62269, United States
Ottawa Illinois, 61350, United States
Pekin Illinois, 61554, United States
Pekin Illinois, 61554, United States
Peoria Illinois, 61615, United States
Peoria Illinois, 61615, United States
Peoria Illinois, 61636, United States
Peoria Illinois, 61637, United States
Peru Illinois, 61354, United States
Peru Illinois, 61354, United States
Princeton Illinois, 61356, United States
Springfield Illinois, 62702, United States
Springfield Illinois, 62702, United States
Springfield Illinois, 62781, United States
Urbana Illinois, 61801, United States
Urbana Illinois, 61801, United States
Warrenville Illinois, 60555, United States
Ames Iowa, 50010, United States
Ames Iowa, 50010, United States
Clive Iowa, 50325, United States
Clive Iowa, 50325, United States
Creston Iowa, 50801, United States
Des Moines Iowa, 50309, United States
Des Moines Iowa, 50309, United States
Des Moines Iowa, 50314, United States
Des Moines Iowa, 50314, United States
Des Moines Iowa, 50314, United States
Des Moines Iowa, 50316, United States
Iowa City Iowa, 52242, United States
West Des Moines Iowa, 50266, United States
West Des Moines Iowa, 50266, United States
Lexington Kentucky, 40504, United States
Lexington Kentucky, 40509, United States
Louisville Kentucky, 40202, United States
Louisville Kentucky, 40207, United States
Louisville Kentucky, 40245, United States
Metairie Louisiana, 70006, United States
Metairie Louisiana, 70006, United States
New Orleans Louisiana, 70112, United States
New Orleans Louisiana, 70112, United States
Bangor Maine, 04401, United States
Brewer Maine, 04412, United States
Baltimore Maryland, 21287, United States
Boston Massachusetts, 02114, United States
Ann Arbor Michigan, 48106, United States
Brighton Michigan, 48114, United States
Brighton Michigan, 48114, United States
Canton Michigan, 48188, United States
Canton Michigan, 48188, United States
Chelsea Michigan, 48118, United States
Detroit Michigan, 48236, United States
Flint Michigan, 48503, United States
Flint Michigan, 48503, United States
Lansing Michigan, 48912, United States
Livonia Michigan, 48154, United States
Pontiac Michigan, 48341, United States
Pontiac Michigan, 48341, United States
Saginaw Michigan, 48601, United States
Warren Michigan, 48093, United States
Ypsilanti Michigan, 48197, United States
Brainerd Minnesota, 56401, United States
Coon Rapids Minnesota, 55433, United States
Deer River Minnesota, 56636, United States
Duluth Minnesota, 55805, United States
Duluth Minnesota, 55805, United States
Duluth Minnesota, 55805, United States
Fridley Minnesota, 55432, United States
Hibbing Minnesota, 55746, United States
Sandstone Minnesota, 55072, United States
Virginia Minnesota, 55792, United States
Ballwin Missouri, 63011, United States
Cape Girardeau Missouri, 63703, United States
Cape Girardeau Missouri, 63703, United States
Creve Coeur Missouri, 63141, United States
Farmington Missouri, 63640, United States
Jefferson City Missouri, 65109, United States
Joplin Missouri, 64804, United States
Rolla Missouri, 65401, United States
Rolla Missouri, 65401, United States
Saint Joseph Missouri, 64506, United States
Saint Louis Missouri, 63110, United States
Saint Louis Missouri, 63128, United States
Saint Louis Missouri, 63129, United States
Saint Louis Missouri, 63131, United States
Saint Louis Missouri, 63136, United States
Saint Louis Missouri, 63141, United States
Saint Peters Missouri, 63376, United States
Sainte Genevieve Missouri, 63670, United States
Springfield Missouri, 65804, United States
Springfield Missouri, 65807, United States
Sullivan Missouri, 63080, United States
Sunset Hills Missouri, 63127, United States
Billings Montana, 59101, United States
Bozeman Montana, 59715, United States
Great Falls Montana, 59405, United States
Great Falls Montana, 59405, United States
Kalispell Montana, 59901, United States
Missoula Montana, 59804, United States
Grand Island Nebraska, 68803, United States
Kearney Nebraska, 68847, United States
Omaha Nebraska, 68122, United States
Omaha Nebraska, 68124, United States
Omaha Nebraska, 68130, United States
Omaha Nebraska, 68131, United States
Albuquerque New Mexico, 87106, United States
Cincinnati Ohio, 45220, United States
Cincinnati Ohio, 45242, United States
Columbus Ohio, 43210, United States
Oklahoma City Oklahoma, 73104, United States
Oklahoma City Oklahoma, 73120, United States
Bend Oregon, 97701, United States
Clackamas Oregon, 97015, United States
Clackamas Oregon, 97015, United States
Coos Bay Oregon, 97420, United States
Newberg Oregon, 97132, United States
Portland Oregon, 97213, United States
Portland Oregon, 97225, United States
Allentown Pennsylvania, 18103, United States
Bethlehem Pennsylvania, 18017, United States
Chadds Ford Pennsylvania, 19317, United States
East Stroudsburg Pennsylvania, 18301, United States
Hershey Pennsylvania, 17033, United States
Gaffney South Carolina, 29341, United States
Greer South Carolina, 29651, United States
Spartanburg South Carolina, 29303, United States
Union South Carolina, 29379, United States
Knoxville Tennessee, 37920, United States
Bryan Texas, 77802, United States
Martinsville Virginia, 24112, United States
Aberdeen Washington, 98520, United States
Bellingham Washington, 98225, United States
Bremerton Washington, 98310, United States
Burien Washington, 98166, United States
Centralia Washington, 98531, United States
Edmonds Washington, 98026, United States
Everett Washington, 98201, United States
Issaquah Washington, 98029, United States
Lacey Washington, 98503, United States
Longview Washington, 98632, United States
Seattle Washington, 98107, United States
Seattle Washington, 98122, United States
Sedro-Woolley Washington, 98284, United States
Silverdale Washington, 98383, United States
Vancouver Washington, 98664, United States
Walla Walla Washington, 99362, United States
Ashland Wisconsin, 54806, United States
Ashland Wisconsin, 54806, United States
Eau Claire Wisconsin, 54701, United States
Marshfield Wisconsin, 54449, United States
Minocqua Wisconsin, 54548, United States
Rice Lake Wisconsin, 54868, United States
Stevens Point Wisconsin, 54482, United States
Weston Wisconsin, 54476, United States
Sheridan Wyoming, 82801, United States
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