OVERVIEW
A Phase II Open-Label Study of Sacituzumab Govitecan in Unresectable Locally Advanced/Metastatic Urothelial Cancer (TROPHY U-01)
PROTOCOL SUMMARY
The objective of this study is to evaluate the efficacy and safety of sacituzumab govitecan-hziy monotherapy and with novel combinations in participants with metastatic urothelial cancer (mUC).
View moreParticipation requirements
Age
18 years +
Sex
All
Healthy Volunteers
No
Age
18 years +
Sex
All
Healthy Volunteers
No
Study details
Medical Condition
Metastatic Urothelial Cancer
Gender
N/A
Date
August 2018 - April 2030
Study Type
Interventional
Study Phase
Phase 2
Product
Sacituzumab Govitecan-hziy, Pembrolizumab, Cisplatin, Avelumab, Zimberelimab, Carboplatin, Gemcitabine, Domvanalimab, Enfortumab Vedotin
Eligibility information
Inclusion criteria
- Inclusion Criteria for All Cohorts:
- Female or male individuals, ≥ 18 years of age (19 Years old for South Korea).
- Eastern Cooperative Oncology Group (ECOG) Performance status score of 0 or 1.
- Adequate renal and hepatic function.
- Adequate hematologic parameters without transfusional support.
- Individuals must have a 3-month life expectancy.
- Additional Inclusion Criteria for Cohorts 1 to 6:
- Cohort 1: Have had progression or recurrence of urothelial cancer following receipt of platinum-containing regimen (cisplatin or carboplatin):
- 1. Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease;
- 2. Or received neo/adjuvant platinum-containing therapy for localized muscle-invasive urothelial cancer, with recurrence/progression ≤12 months following completion of therapy.
- Cohort 1: In addition to above criterion, have had progression or recurrence of urothelial cancer following receipt of an Anti-programmed Cell Death Protein 1 (anti-PD-1)/ Anti-programmed Death Ligand 1 (PD-L1) therapy.
- Cohort 2: Were ineligible for platinum-based therapy for first line metastatic disease and have had progression or recurrence of urothelial cancer after a first-line therapy for metastatic disease with anti-PD-1/PD-L1 therapy. Individual may not have received any platinum for treatment of recurrent, metastatic or advanced disease.
- Cohort 3: Progression or recurrence of UC following a platinum containing regimen in the metastatic setting, or progression or recurrence of UC within 12 months of completion of platinum-based therapy as neoadjuvant or adjuvant therapy.
- Cohort 4: Individual has not received any platinum-based chemotherapy in the metastatic or unresectable locally advanced setting. Creatinine clearance of at least 50 mL/min calculated by Cockcroft-Gault formula or another validated tool. For individuals receiving cisplatin at 70 mg/m^2 on Day 1 of every 21-day cycle, a creatinine clearance of least 60 mL/min calculated by Cockcroft -Gault formula or another validated tool is required. Individuals with creatinine clearance between 50 to 59 mL/min are to receive a split dose of cisplatin (35 mg/m^2 Day 1 and Day 8 of every 21-day cycle).
- Cohorts 4, 5, 6: Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma.
- Cohort 5: Individuals received at least 4 cycles and no more than 6 cycles of GEM + cisplatin. No other chemotherapy regimens are allowed in this cohort, with the exception of prior adjuvant or neoadjuvant systemic therapy with curative intent after > 12 months from completion of therapy.
- No evidence of progressive disease following completion of first-line chemotherapy (ie, CR, PR, or SD per RECIST v1.1 guidelines as per investigator).
- Treatment-free interval of 4 to 10 weeks since the last dose of chemotherapy.
- Cohort 6: Cis-ineligible and no prior therapy for metastatic disease or for unresectable locally advanced disease. Checkpoint inhibitor therapy naïve or >12 months from completion of adjuvant therapy are permitted.
- Cohorts 4 and 6: Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- Cohorts 1, 2, 3 and 5: Creatinine clearance ≥ 30 mL/min as calculated by the Cockcroft-Gault formula unless otherwise specified
- Additional Inclusion Criteria for Cohort 7:
- No prior systemic therapy for locally advanced or metastatic UC. Therapy in the curative setting is allowed provided recurrence is > 12 months since the last dose of systemic therapy.
- Archival tumor tissue comprising muscle-invasive or metastatic urothelial carcinoma, or a biopsy of metastatic urothelial carcinoma.
- Have measurable disease by CT or MRI as per RECIST 1.1 criteria. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Exclusion criteria
- Exclusion Criteria for All cohorts:
- Females who are pregnant or lactating.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- Has an active second malignancy.
- Has known active Hepatitis B or Hepatitis C.
- Has other concurrent medical or psychiatric conditions.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Has an active second malignancy.
- Additional Exclusion Criteria for Cohorts 1 to 6:
- For Cohort 5: Alopecia, sensory neuropathy Grade ≤2 is acceptable, or other Grade << 2 adverse events not constituting a safety risk based on the investigator's judgment are acceptable.
- Cohort 3: Has received anti-PD-1/PD-L1 therapy previously.
- Cohorts 3 to 6: Has an active autoimmune disease that required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- Cohorts 3 to 6: Has received a live vaccine within 30 days prior to the first dose of study drug(s), has history or evidence of interstitial lung disease (ILD) or non-infectious pneumonitis.
- Cohort 4: Refractory to platinum (i.e., relapsed ≤ 12 months after completion of chemotherapy) in the neoadjuvant/adjuvant setting.
- Cohorts 4, 5, and 6: For individuals who received prior CPI, a treatment-free interval >12 months between the last treatment administration and the date of recurrence is required.
- Additional Exclusion Criteria for Cohort 7:
- Have had a prior anticancer therapy within 12 months prior to C1D1 or prior radiation therapy within 2 weeks prior to C1D1. Individuals participating in observational studies are eligible. Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of investigational product.
- Have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
- Have a Child-Pugh score of B or C.
- Individuals with uncontrolled diabetes.
- Have active keratitis or corneal ulcerations.
- Participants with ongoing sensory or motor neuropathy Grade ≥ 2.
- Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Locations
Locations (135)
The University of Arizona Cancer Center-North Campus
Tucson, Arizona, United States, 85719
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
University of California San Francisco
San Francisco, California, United States, 94158
Rocky Mountain Cancer Centers
Littleton, Colorado, United States, 80120
Smilow Cancer Hospital at Yale-New Haven
New Haven, Connecticut, United States, 06510
Eastern Connecticut Hematology and Oncology Associates
Norwich, Connecticut, United States, 06360
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States, 33140
Woodlands Medical Specialists, PA
Pensacola, Florida, United States, 32503
Winship Cancer Institute, Emory University
Atlanta, Georgia, United States, 30322
University of Illinois Cancer Center
Chicago, Illinois, United States, 60612
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
Southern Illinois University School of Medicine, Simmons Cancer Institute
Springfield, Illinois, United States, 62702
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Norton Cancer Institute, Downtown
Louisville, Kentucky, United States, 40202
Maryland Oncology Hematology, P.A.
Brandywine, Maryland, United States, 20613
University of Michigan
Ann Arbor, Michigan, United States, 48109
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Oncology Hematology West PC dba Nebraska Cancer Specialists
Omaha, Nebraska, United States, 68130
Precision Cancer Research / New Mexico Oncology & Hematology Consultants
Albuquerque, New Mexico, United States, 87109
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, United States, 10016
Drug Shipping Address: New York-Presbyterian Hospital
New York, New York, United States, 10065
Stony Brook Cancer Center
Stony Brook, New York, United States, 11794
St. Luke's Hosptial - Bethlehem Campus
Easton, Pennsylvania, United States, 18045
Medical University of Southern Carolina
Charleston, South Carolina, United States, 29425
Thompson Oncology Group - Knoxville West
Knoxville, Tennessee, United States, 37932
Henry-Joyce Cancer Clinic
Nashville, Tennessee, United States, 37232
Houston Methodist Hospital, Houston Methodist Cancer Center
Houston, Texas, United States, 77030
University of Utah - Huntsman Cancer Hospital (IP Shipping Address)
Salt Lake City, Utah, United States, 84112
University of Virginia Cancer Center
Charlottesville, Virginia, United States, 22903
Virginia Oncology Associates
Hampton, Virginia, United States, 23666
Oncology Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care
Roanoke, Virginia, United States, 24014
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
University of Wisconsin Clinical Science Center
Madison, Wisconsin, United States, 53705
Centre Hospitalier Regional Universitaire (CHRU) de Besancon, Hopital Jean Minjoz
Besançon, France, 25000
Centre Hospitalier Regional Universitaire Brest
Brest, France, 29200
Centre Hospitalier Departmental (CHD) Vendee
La Roche-sur-Yon, France, 85925
Centre Hospitalier Universitaire De Nimes - Hopital Universitaire Caremeau
Nîmes, France, 30029
Hospitaux Universitaires de Strasbourg - Hopital Civil
Strasbourg, France, 67200
Institut de Cancerologie de Lorraine
Vandœuvre-lès-Nancy, France, 54519
Centrum fur Hamatologie und Onkologie Bethanien
Frankfurt, Germany, 60389
Universitätsklinikum Frankfurt, Klinik für Urologie
Frankfurt, Germany, 60590
Universitatsklinikum Freiburg
Freiburg im Breisgau, Germany, 79106
Institut für Versorgungsforschung in der Onkologie
Koblenz, Germany, 56068
Universitätsklinikum Carl Gustav Carus an der TU Dresden
Mainz, Germany, 55131
Klinikum rechts der Isar der Technischen Universität München, Urologische Klinik und Poloklinik
München, Germany, 81675
Universitatsklinikum Munster, Klinik fur Urologie und Kinderurologie
Münster, Germany, 48149
Universitatsklinikum Tubingen, Klinik fur Urologie
Tübingen, Germany, 72076
Henry Dunant Hospital Center, 4th Oncology Department
Athens, Greece, 11526
University General Hospital of Ioannina, Oncology Department
Ioannina, Greece, 45500
Athens Medical Center, Oncology Department
Marousi, Greece, 15125
Anassa General Clinic, Oncology-Chemotherapy Department
Volos, Greece, 38333
Istituto Romagnolo per Io Studio dei Tumori (IRST) "Dino Amadori"
Meldola, Italy, 47014
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy, 20133
Azienda Ospedaliero Universitaria Maggiore della Carita
Novara, Italy, 28100
Istituto Oncologico Veneto IRCCS - Ospedale Busonera
Padova, Italy, 35128
Instituto Nazionale Tumori Regina Elena - IFO
Roma, Italy, 00144
Kyungpook National University Chilgok Hospital
Daegu, South Korea, 41404
Chonnam National University Hospital
Gwangju, South Korea, 61469
Chonnam National University Hwasun Hospital
Hwasun, South Korea, 519-763
Yonsei University Health System, Severance Hospital
Seoul, South Korea, 03722
The Catholic University of Korea, St. Vincent's Hospital
Suwon, South Korea, 16247
Yonsei University - Wonju Severance Christian Hospital
Wŏnju, South Korea, 26426
Pusan National University Yangsan Hospital
Yangsan, South Korea, 50612
Institut Catala d'Oncologia Badalona - Hospital Universitari Germans Trias i Pujol
Badalona, Spain, 08916
Complejo Hospitalario Universitario Insular Materno Infantil
Las Palmas, Spain, 35016
Hospital Universitario Puera de Hierro Majadahonda
Majadahonda, Spain, 28222
Hospital Universitario Marques de Valdecilla
Santander, Spain, 39008
Complejo Hospitalario Universitario de Santiago
Santiago de Compostela, Spain, 15706
Hospital Clinico Universitario de Valencia
Valencia, Spain, 46010
Dicle Universitesi Tip Fakultesi Hastanesi
Diyarbakır, Turkey (Türkiye), 21280
Trakya Universitesi Saglik Arastirma ve Uygulama Merkezi
Edrine, Turkey (Türkiye), 22030
Istanbul Universitesi Cerrahpasa Tip Fakultesi Hastanesi
Istanbul, Turkey (Türkiye), 34098
Medipol Mega Universite Hastanesi
Istanbul, Turkey (Türkiye), 34214
T.C. Saglik Bakanligi Goztepe Prof Dr. Suleyman Yalcin Sehir Hastanesi
Istanbul, Turkey (Türkiye), 34722
Izmir Medical Point Hastanesi, Medikal Onkoloji Departmant
Izmir, Turkey (Türkiye), 35575
Baskent Universitesi Adana Dr.Turgut Noyan Uygulama ve Arastima Merkezi
Seyhan, Turkey (Türkiye), 01250
University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom, B9 5SS
East and North Hertfordshire NHS Trust
Northwood, United Kingdom, HA6 2JW
The Royal Marsden NHS Foundation Trust
Surrey, United Kingdom, SM2 5PT
Join Gilead Trial Connect and help advance clinical research. Your participation is key to developing future treatments.
Share Trial