Upper Urinary Tract Cancer

EA8192



Testing the Addition of MEDI4736 (Durvalumab) to Chemotherapy before Surgery for Patients with High-Grade Upper Urinary Tract Cancer

STATUS: Active


This phase II/III trial compares the effect of adding durvalumab to chemotherapy versus chemotherapy alone before surgery in treating patients with upper urinary tract cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the bodyโ€™s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as methotrexate, vinblastine, doxorubicin, cisplatin, and gemcitabine 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. Durvalumab in combination with chemotherapy before surgery may enhance the shrinking of the tumor compared to chemotherapy alone.
  • STEP 1 REGISTRATION AND RANDOMIZATION

  • Patients must be >= 18 years of age

  • Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible

  • Patient must have a diagnosis of high grade upper tract urothelial carcinoma proven by biopsy within 12 weeks (84 days) prior to registration/randomization with one of the following: * Upper urinary tract mass on cross-sectional imaging or * Tumor directly visualized during upper urinary tract endoscopy before referral to medical oncology ** NOTE: Biopsy is standard of care (SOC) and required for enrollment to study. This is vital for best practice

  • Patients must not have any component of small cell/neuroendocrine carcinoma. Other variant histologic types are permitted provided the predominant (>= 50%) subtype is urothelial carcinoma

  • Leukocytes >= 3,000/mcL (obtained =< 14 days prior to registration/randomization)

  • Platelets >= 100,000/mcL (obtained =< 14 days prior to registration/randomization)

  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (or =< 2.5 x ULN for patients with Gilbertโ€™s disease) (obtained =< 14 days prior to registration/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 registration/randomization)

  • Hemoglobin (Hgb) >= 9 g/dL (obtained =< 14 days prior to registration/randomization) * NOTE: Packed red blood transfusion is allowed to achieve this parameter as per treating investigator

  • Patients 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 registration 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 of childbearing potential and sexually active patients must not expect to conceive or father children, either by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of registration, while on study treatment and for at least 6 months after the last dose of protocol treatment

  • Patients must have no evidence of metastatic disease or clinically enlarged regional lymph nodes (>= 1.5 cm short axis) on imaging required within 28 days prior to registration (Non-regional findings >=1.5 cm short axis that in the opinion of the investigator are not concerning for involvement based on radiographic characteristics, chronicity, avidity on positron emission tomography (PET) or other imaging or other criteria can be eligible based on investigator discretion). * NOTE: Patients with elevated alkaline phosphatase, calcium or suspicious bone pain/tenderness can also undergo baseline bone scans to evaluate for bone metastasis at the discretion of local provider.

  • Patient must meet below criteria for prior/current malignancy history: * Non-urothelial cancer malignancy history: ** Patient must not have another active (or within two years) second malignancy other than resected non-melanoma skin cancers, resected in situ breast, cervical or other in situ carcinoma, and either clinically insignificant per the investigator (e.g. =< Gleason 3+4) on active surveillance (or watchful waiting) or previously treated prostate cancer with no rising prostate specific antigen (PSA) and no plan to treat *** NOTE: 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. Patients in whom concomitant or prior bladder/urethra predominant (>= 50%) urothelial carcinoma have been surgically resected and demonstrated to be only non-invasive cancer (< cT1N0) are eligible regardless of time elapsed ** Urothelial cancer malignancy history: *** Patient may have a history of resectable urothelial cancer as long as patients meet one of the following: *** T0, Ta or Tis at any time *** T1-4a N0 and no evidence of disease (NED) for more than 2 years from the latest therapy [e.g., radical surgery, transurethral resection of bladder tumor (TURBT), radiation, chemotherapy (neoadjuvant or adjuvant, or with radiation)]. Prior immune checkpoint inhibitor is not allowed. *** Patient with history of >= pT4b, N+, and/or M1 is not eligible. *** NOTE: Patients in whom concomitant or prior bladder/urethra predominant (>= 50%) urothelial carcinoma have been surgically resected and demonstrated to be only Ta or carcinoma in situ (CIS) (< cT1 N0) are eligible regardless of time elapsed

  • Patient must not have any uncontrolled illness including, but not limited to, ongoing or active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis [TB] testing in line with local practice), symptomatic congestive heart failure (CHF), myocardial infarction (MI) in last three months, or unstable angina pectoris, significant uncontrolled cardiac arrhythmia, clinically relevant liver cirrhosis, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirements

  • Patient must not have received prior radiation therapy to >= 25% of the bone marrow for other diseases

  • Patient must not have received prior systemic anthracycline therapy * NOTE: Patients who have received prior intravesical chemotherapy at any time for non-muscle invasive urothelial carcinoma of the bladder are eligible

  • Patient must not have either history of or active autoimmune disease requiring immunosuppressive therapy within 2 years prior to registration/randomization or any history of inflammatory bowel disease (inflammatory bowel disease [IBD], colitis, or Crohnโ€™s disease), neuromuscular autoimmune condition, immune-related pneumonitis or interstitial lung disease. Patients with well-controlled hyper/hypothyroidism, celiac controlled by diet alone, diabetes mellitus type I, vitiligo, alopecia, psoriasis, eczema, lichen planus, or similar skin/mucosa condition are eligible

  • Patient must not be on or have used immunosuppressive medication within 14 days prior to the first dose of durvalumab. The following are exceptions to this criterion: * Intranasal, inhaled, intra-auricular, 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 at the time of enrollment * Steroids as premedications for hypersensitivity reactions (e.g. computed tomography [CT] scan premedication)

  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration/randomization are eligible for this trial * NOTE: These patients must be stable on their anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on the same regimen; the most recent undetectable viral load must be within the past 12 weeks. They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count < 200 cells/mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy induced bone marrow suppression. They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months * NOTE: For patients who have received chemotherapy in the past 6 months, a CD4 count < 250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy. They must have an undetectable viral load and a CD4 count >= 250 cells/mcL within 7 days of registration/randomization

  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated * NOTE: Testing for HIV, hepatitis B or hepatitis C is not required unless clinically indicated

  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and have undetectable viral load. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

  • 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 2B or better

  • Patient must not have received live attenuated vaccine within 30 days prior to the first dose of durvalumab, while on protocol treatment and within 30 days after the last dose of durvalumab

  • Patient must not have had a major surgical procedure within 28 days prior to registration/randomization * NOTE: Cystoscopy/ureteroscopy, stent placement or nephrostomy tube is not considered major surgery

  • Patient must not have history of allogenic organ transplantation

  • Patient must have a body weight of > 30 kg

  • Patient must have life expectancy of >= 12 weeks

  • Patient must have creatinine clearance > 15 ml/min as by Crockroft-Gault formula or 24-hour creatinine clearance within 28 days prior to registration/randomization * NOTE: Patients will be assigned to cisplatin-ineligible and cisplatin-eligible cohorts based on their creatinine clearance, Eastern Cooperative Oncology Group (ECOG) performance status, and grade (if any) of peripheral neuropathy and/or hearing loss in keeping with SOC cisplatin contraindications. Patients that are cisplatin-eligible will be randomized to either Arm A or Arm B ** Patients that meet any of the following criteria will be registered and assigned to the cisplatin-ineligible Arm C if they meet other eligibility criteria: *** Creatinine clearance > 15 ml/min and =< 50 ml/min or hearing loss grade >= 3, or neuropathy >= 2, or ECOG PS 2 *** Patient must have an absolute neutrophil count (ANC) >= 1,000/mcL obtained =< 14 days prior to registration *** Patient must have ECOG performance status 0-2 ** Patients that meet the following criteria will be randomized to the cisplatin-eligible Arm A or Arm B: *** Patient must have creatinine clearance of > 50ml/min, PS ECOG 0-1, absence of hearing loss grade >= 3, and/or neuropathy >= 2 *** Patient must have an absolute neutrophil count (ANC) >= 1,500/mcL obtained =< 14 days prior to randomization *** Patient must have left ventricular ejection fraction (LVEF) >= 50% by (either multigated acquisition scan [MUGA] or 2-D echocardiogram) obtained within obtained within 28 days prior to randomization

United States
AR
Ft. Smith
Mercy Hospital Fort Smith
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Little Rock
University of Arkansas for Medical Sciences
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CA
Auburn
Sutter Auburn Faith Hospital
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Berkeley
Alta Bates Summit Medical Center-Herrick Campus
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Duarte
City of Hope Comprehensive Cancer Center
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Email: becomingapatient@coh.org

Fremont
Palo Alto Medical Foundation-Fremont
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Email: Melanie.Cook@sutterhealth.org

Modesto
Memorial Medical Center
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Mountain View
Palo Alto Medical Foundation-Camino Division
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Palo Alto
Palo Alto Medical Foundation Health Care
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Roseville
Sutter Roseville Medical Center
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Sacramento
Sutter Medical Center Sacramento
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San Francisco
California Pacific Medical Center-Pacific Campus
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Santa Cruz
Palo Alto Medical Foundation-Santa Cruz
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Email: Melanie.Cook@sutterhealth.org

Sunnyvale
Palo Alto Medical Foundation-Sunnyvale
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Email: Melanie.Cook@sutterhealth.org

Vallejo
Sutter Solano Medical Center/Cancer Center
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CO
Aurora
UCHealth University of Colorado Hospital
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Fort Collins
Cancer Care and Hematology-Fort Collins
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Poudre Valley Hospital
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Greeley
UCHealth Greeley Hospital
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Highlands Ranch
UCHealth Highlands Ranch Hospital
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Loveland
Medical Center of the Rockies
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DC
Washington
MedStar Washington Hospital Center
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Sibley Memorial Hospital
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FL
Jacksonville
Mayo Clinic in Florida
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GA
Atlanta
Emory University Hospital Midtown
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Emory University Hospital/Winship Cancer Institute
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IA
Ames
Mary Greeley Medical Center
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McFarland Clinic - Ames
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Email: ksoder@mcfarlandclinic.com

Bettendorf
University of Iowa Healthcare Cancer Services Quad Cities
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Boone
McFarland Clinic - Boone
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Fort Dodge
McFarland Clinic - Trinity Cancer Center
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Iowa City
University of Iowa/Holden Comprehensive Cancer Center
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Jefferson
McFarland Clinic - Jefferson
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Marshalltown
McFarland Clinic - Marshalltown
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IL
Alton
Saint Anthony's Health
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Barrington
Advocate Good Shepherd Hospital
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Bloomington
Illinois CancerCare-Bloomington
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Burr Ridge
Loyola Center for Health at Burr Ridge
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Canton
Illinois CancerCare-Canton
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Carbondale
Memorial Hospital of Carbondale
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Carterville
SIH Cancer Institute
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Carthage
Illinois CancerCare-Carthage
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Centralia
Centralia Oncology Clinic
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Chicago
Advocate Illinois Masonic Medical Center
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Crystal Lake
AMG Crystal Lake - Oncology
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Danville
Carle at The Riverfront
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Email: Research@Carle.com

Decatur
Cancer Care Specialists of Illinois - Decatur
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Email: morganthaler.jodi@mhsil.com

Decatur Memorial Hospital
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Dixon
Illinois CancerCare-Dixon
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Downers Grove
Advocate Good Samaritan Hospital
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Email: Barbara.barhamand@advocatehealth.com

Effingham
Carle Physician Group-Effingham
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Email: Research@carle.com

Crossroads Cancer Center
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Elgin
Advocate Sherman Hospital
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Eureka
Illinois CancerCare-Eureka
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Galesburg
Illinois CancerCare-Galesburg
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Email: andersonj@illinoiscancercare.com

Western Illinois Cancer Treatment Center
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Hazel Crest
Advocate South Suburban Hospital
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Homer Glen
Loyola Medicine Homer Glen
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Kewanee
Illinois CancerCare-Kewanee Clinic
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Email: andersonj@illinoiscancercare.com

Libertyville
AMG Libertyville - Oncology
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Email: advocateresearch@advocatehealth.com

Macomb
Illinois CancerCare-Macomb
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Email: andersonj@illinoiscancercare.com

Mattoon
Carle Physician Group-Mattoon/Charleston
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Email: Research@carle.com

Maywood
Loyola University Medical Center
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Melrose Park
Marjorie Weinberg Cancer Center at Loyola-Gottlieb
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Mount Vernon
Good Samaritan Regional Health Center
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O'Fallon
Cancer Care Center of O'Fallon
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Email: morganthaler.jodi@mhsil.com

Oak Lawn
Advocate Christ Medical Center
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Ottawa
Illinois CancerCare-Ottawa Clinic
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Email: andersonj@illinoiscancercare.com

Park Ridge
Advocate Lutheran General Hospital
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Pekin
Illinois CancerCare-Pekin
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Peoria
Illinois CancerCare-Peoria
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Methodist Medical Center of Illinois
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Peru
Illinois CancerCare-Peru
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Email: andersonj@illinoiscancercare.com

Valley Radiation Oncology
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Princeton
Illinois CancerCare-Princeton
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Springfield
Memorial Medical Center
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Email: pallante.beth@mhsil.com

Southern Illinois University School of Medicine
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Springfield Clinic
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Urbana
Carle Cancer Center
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Email: Research@carle.com

Washington
Illinois CancerCare - Washington
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Email: andersonj@illinoiscancercare.com

IN
Richmond
Reid Health
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Email: clinical.trials@daytonncorp.org

KS
Garden City
Central Care Cancer Center - Garden City
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Email: aroland@kccop.org

Great Bend
Central Care Cancer Center - Great Bend
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Email: aroland@kccop.org

KY
Lexington
University of Kentucky/Markey Cancer Center
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LA
Metairie
East Jefferson General Hospital
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Email: emede1@lsuhsc.edu

LSU Healthcare Network / Metairie Multi-Specialty Clinic
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MA
Worcester
UMass Memorial Medical Center - University Campus
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MD
Baltimore
Johns Hopkins University/Sidney Kimmel Cancer Center
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Email: jhcccro@jhmi.edu

ME
Augusta
Harold Alfond Center for Cancer Care
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Biddeford
MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford
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Email: LLemire@mmc.org

Sanford
MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford
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Email: LLemire@mmc.org

South Portland
Maine Medical Partners - South Portland
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Email: ClinicalResearch@mmc.org

MI
Ann Arbor
Saint Joseph Mercy Hospital
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Email: MCRCwebsitecontactform@stjoeshealth.org

Brighton
Saint Joseph Mercy Brighton
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Email: MCRCwebsitecontactform@stjoeshealth.org

Trinity Health IHA Medical Group Hematology Oncology - Brighton
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Canton
Saint Joseph Mercy Canton
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Trinity Health IHA Medical Group Hematology Oncology - Canton
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Chelsea
Saint Joseph Mercy Chelsea
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Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
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Clarkston
Newland Medical Associates-Clarkston
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Flint
Genesee Cancer and Blood Disease Treatment Center
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Email: wstrong@ghci.org

Genesee Hematology Oncology PC
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Email: wstrong@ghci.org

Genesys Hurley Cancer Institute
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Email: wstrong@ghci.org

Livonia
Hope Cancer Clinic
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Trinity Health Saint Mary Mercy Livonia Hospital
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Pontiac
21st Century Oncology-Pontiac
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Newland Medical Associates-Pontiac
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Ypsilanti
Huron Gastroenterology PC
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Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
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MN
Burnsville
Fairview Ridges Hospital
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Email: mmcorc@healthpartners.com

Minnesota Oncology - Burnsville
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Email: mmcorc@healthpartners.com

Cambridge
Cambridge Medical Center
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Coon Rapids
Mercy Hospital
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Edina
Fairview Southdale Hospital
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Fridley
Unity Hospital
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Maple Grove
Fairview Clinics and Surgery Center Maple Grove
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Maplewood
Minnesota Oncology Hematology PA-Maplewood
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Email: mmcorc@healthpartners.com

Saint John's Hospital - Healtheast
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Minneapolis
Abbott-Northwestern Hospital
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Health Partners Inc
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Hennepin County Medical Center
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Monticello
Monticello Cancer Center
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New Ulm
New Ulm Medical Center
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Princeton
Fairview Northland Medical Center
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Robbinsdale
North Memorial Medical Health Center
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Rochester
Mayo Clinic in Rochester
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Saint Louis Park
Park Nicollet Clinic - Saint Louis Park
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Email: mmcorc@healthpartners.com

Saint Paul
Regions Hospital
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Email: mmcorc@healthpartners.com

United Hospital
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Shakopee
Saint Francis Regional Medical Center
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Stillwater
Lakeview Hospital
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Email: mmcorc@healthpartners.com

Waconia
Ridgeview Medical Center
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Email: mmcorc@healthpartners.com

Willmar
Rice Memorial Hospital
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Email: mmcorc@healthpartners.com

Woodbury
Minnesota Oncology Hematology PA-Woodbury
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Email: mmcorc@healthpartners.com

Wyoming
Fairview Lakes Medical Center
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Email: mmcorc@healthpartners.com

MO
Ballwin
Saint Louis Cancer and Breast Institute-Ballwin
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Bolivar
Central Care Cancer Center - Bolivar
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Email: aroland@kccop.org

Cape Girardeau
Saint Francis Medical Center
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Email: sfmc@sfmc.net

Southeast Cancer Center
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Farmington
Parkland Health Center - Farmington
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Jefferson City
Capital Region Southwest Campus
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Email: swooden@mail.crmc.org

Joplin
Freeman Health System
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Email: LJCrockett@freemanhealth.com

Mercy Hospital Joplin
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Email: esmeralda.carrillo@mercy.net

Rolla
Delbert Day Cancer Institute at PCRMC
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Email: research@phelpshealth.org

Mercy Clinic-Rolla-Cancer and Hematology
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Saint Joseph
Heartland Regional Medical Center
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Email: linda.schumacher@mymlc.com

Saint Louis
Mercy Hospital Saint Louis
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Mercy Hospital South
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Email: Danielle.Werle@mercy.net

Missouri Baptist Medical Center
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Saint Louis Cancer and Breast Institute-South City
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Sainte Genevieve
Sainte Genevieve County Memorial Hospital
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Springfield
CoxHealth South Hospital
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Mercy Hospital Springfield
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Sullivan
Missouri Baptist Sullivan Hospital
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Sunset Hills
Missouri Baptist Outpatient Center-Sunset Hills
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Washington
Mercy Hospital Washington
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NC
Clinton
Southeastern Medical Oncology Center-Clinton
Contact: Site Public Contact
Email: jfields@cancersmoc.com

Goldsboro
Southeastern Medical Oncology Center-Goldsboro
Contact: Site Public Contact
Email: jfields@cancersmoc.com

Jacksonville
Southeastern Medical Oncology Center-Jacksonville
Contact: Site Public Contact
Email: jfields@cancersmoc.com

Winston-Salem
Wake Forest University Health Sciences
Contact: Site Public Contact

NJ
Hackensack
Hackensack University Medical Center
Contact: Site Public Contact

Livingston
Saint Barnabas Medical Center
Contact: Site Public Contact
Email: joanne.loeb@rwjbh.org

New Brunswick
Rutgers Cancer Institute of New Jersey
Contact: Site Public Contact

NM
Albuquerque
University of New Mexico Cancer Center
Contact: Site Public Contact
Email: HSC-ClinicalTrialInfo@salud.unm.edu

NV
Henderson
OptumCare Cancer Care at Seven Hills
Contact: Site Public Contact
Email: research@sncrf.org

Las Vegas
OptumCare Cancer Care at Charleston
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Email: research@sncrf.org

OptumCare Cancer Care at Fort Apache
Contact: Site Public Contact
Email: research@sncrf.org

NY
Buffalo
Roswell Park Cancer Institute
Contact: Site Public Contact
Email: askroswell@roswellpark.org

OH
Centerville
Dayton Physicians LLC-Miami Valley South
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Miami Valley Hospital South
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Dayton
Dayton Blood and Cancer Center
Contact: Site Public Contact

Dayton Physician LLC-Miami Valley Hospital North
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Miami Valley Hospital
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Miami Valley Hospital North
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Findlay
Armes Family Cancer Center
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Franklin
Atrium Medical Center-Middletown Regional Hospital
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Dayton Physicians LLC-Atrium
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Kettering
Greater Dayton Cancer Center
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Kettering Medical Center
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Springfield
Springfield Regional Cancer Center
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Troy
Upper Valley Medical Center
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

OK
Lawton
Cancer Centers of Southwest Oklahoma Research
Contact: Site Public Contact

Oklahoma City
Mercy Hospital Oklahoma City
Contact: Site Public Contact

University of Oklahoma Health Sciences Center
Contact: Site Public Contact
Email: ou-clinical-trials@ouhsc.edu

PA
Erie
UPMC Hillman Cancer Center Erie
Contact: Site Public Contact
Email: haneydl@upmc.edu

Greensburg
UPMC Cancer Centers - Arnold Palmer Pavilion
Contact: Site Public Contact

Monroeville
UPMC Hillman Cancer Center - Monroeville
Contact: Site Public Contact
Email: haneydl@upmc.edu

Philadelphia
Thomas Jefferson University Hospital
Contact: Site Public Contact
Email: ONCTrialNow@jefferson.edu

Pittsburgh
UPMC-Passavant Hospital
Contact: Site Public Contact

UPMC-Saint Clair Hospital Cancer Center
Contact: Site Public Contact

University of Pittsburgh Cancer Institute (UPCI)
Contact: Site Public Contact

Washington
UPMC Cancer Center-Washington
Contact: Site Public Contact
Email: ecog.rss@jimmy.harvard.edu

SC
Charleston
Medical University of South Carolina
Contact: Site Public Contact
Email: hcc-clinical-trials@musc.edu

TX
Dallas
Parkland Memorial Hospital
Contact: Site Public Contact
Email: canceranswerline@UTSouthwestern.edu

UT Southwestern Simmons Cancer Center - RedBird
Contact: Site Public Contact
Email: canceranswerline@utsouthwestern.edu

UT Southwestern/Simmons Cancer Center-Dallas
Contact: Site Public Contact
Email: canceranswerline@UTSouthwestern.edu

Fort Worth
UT Southwestern/Simmons Cancer Center-Fort Worth
Contact: Site Public Contact
Email: canceranswerline@UTSouthwestern.edu

Richardson
UT Southwestern Clinical Center at Richardson/Plano
Contact: Site Public Contact
Email: Suzanne.cole@utsouthwestern.edu

WI
Appleton
ThedaCare Regional Cancer Center
Contact: Site Public Contact
Email: ResearchDept@thedacare.org

Burlington
Aurora Cancer Care-Southern Lakes VLCC
Contact: Site Public Contact
Email: ncorp@aurora.org

Eau Claire
Marshfield Medical Center-EC Cancer Center
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Germantown
Aurora Health Care Germantown Health Center
Contact: Site Public Contact
Email: ncorp@aurora.org

Grafton
Aurora Cancer Care-Grafton
Contact: Site Public Contact
Email: ncorp@aurora.org

Green Bay
Aurora BayCare Medical Center
Contact: Site Public Contact
Email: ncorp@aurora.org

Kenosha
Aurora Cancer Care-Kenosha South
Contact: Site Public Contact
Email: ncorp@aurora.org

Marinette
Aurora Bay Area Medical Group-Marinette
Contact: Site Public Contact
Email: ncorp@aurora.org

Marshfield
Marshfield Medical Center-Marshfield
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Milwaukee
Aurora Cancer Care-Milwaukee
Contact: Site Public Contact
Email: ncorp@aurora.org

Aurora Saint Luke's Medical Center
Contact: Site Public Contact
Email: ncorp@aurora.org

Aurora Sinai Medical Center
Contact: Site Public Contact
Email: ncorp@aurora.org

Minocqua
Marshfield Clinic-Minocqua Center
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Mukwonago
ProHealth D N Greenwald Center
Contact: Site Public Contact
Email: research.institute@phci.org

New Richmond
Cancer Center of Western Wisconsin
Contact: Site Public Contact
Email: mmcorc@healthpartners.com

Oconomowoc
ProHealth Oconomowoc Memorial Hospital
Contact: Site Public Contact

Oshkosh
Vince Lombardi Cancer Clinic - Oshkosh
Contact: Site Public Contact
Email: ncorp@aurora.org

Racine
Aurora Cancer Care-Racine
Contact: Site Public Contact
Email: ncorp@aurora.org

Rice Lake
Marshfield Medical Center-Rice Lake
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Sheboygan
Vince Lombardi Cancer Clinic-Sheboygan
Contact: Site Public Contact
Email: ncorp@aurora.org

Stevens Point
Marshfield Medical Center-River Region at Stevens Point
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Summit
Aurora Medical Center in Summit
Contact: Site Public Contact
Email: ncorp@aurora.org

Two Rivers
Vince Lombardi Cancer Clinic-Two Rivers
Contact: Site Public Contact
Email: ncorp@aurora.org

Waukesha
ProHealth Waukesha Memorial Hospital
Contact: Site Public Contact

UW Cancer Center at ProHealth Care
Contact: Site Public Contact
Email: Chanda.miller@phci.org

Waupaca
ThedaCare Cancer Care - Waupaca
Contact: Site Public Contact
Email: ResearchDept@thedacare.org

Wauwatosa
Aurora Cancer Care-Milwaukee West
Contact: Site Public Contact
Email: ncorp@aurora.org

West Allis
Aurora West Allis Medical Center
Contact: Site Public Contact
Email: ncorp@aurora.org

Weston
Marshfield Medical Center - Weston
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

PRIMARY OBJECTIVES:
I. To compare event-free survival (EFS) between patients with upper tract urothelial cancer (UTUC) randomized to neoadjuvant accelerated methotrexate, vinblastine, adriamycin, cisplatin (aMVAC) alone or in combination with durvalumab. (Cisplatin eligible patients [Arms A and B])
II. Evaluation of pathologic complete response at radical nephroureterectomy (RNU) (pathologic complete response [pCR], pT0N0/ Nx). (Cisplatin ineligible patients [Arm C]).

SECONDARY OBJECTIVES:
I. To assess pathologic complete response (pCR) at surgery. (Cisplatin eligible cohort)
II. Event-free survival (EFS) will be evaluated for the cisplatin ineligible cohort as a secondary endpoint. (Cisplatin ineligible cohort)
III. Overall survival in all, and by post chemotherapy response (ypCR, yp =< T1N0, yp >= T2Nany). (All patients)
IV. To evaluate disease-free survival (DFS) in each arm of the trial separately. (All patients)
V. To evaluate cancer-specific survival of patients in each arm of the trial separately. (All patients)
VI. To evaluate renal function outcomes following systemic treatment and following surgery ([RNU) in each arm of the trial separately. (All patients)
VII. To evaluate safety and tolerability of neoadjuvant aMVAC alone or in combination with durvalumab prior to RNU. (All patients)

OUTLINE: Patients eligible for cisplatin are randomized to Arms A or B. Patients ineligible for cisplatin are assigned to Arm C.

ARM A: Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of chemotherapy cycles 1 and 3. Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.

ARM B: Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.

ARM C: Patients receive durvalumab IV over 60 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.

Patients also undergo tissue biopsy and blood sample collection on study, and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial.

After completion of study treatment, patients are followed up within 30 days and then every 3-6 months for up to 5 years from study entry.

Interactive content above is from the official study record on the National Cancer Institute website, cancer.gov.


The ECOG-ACRIN Cancer Research Group designed this trial and is conducting it with funding from the National Cancer Institute through its National Clinical Trials Network.


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