Intravesical BCG vs GEMDOCE in NMIBC

Non-muscle-invasive Bladder Cancer Clinical Trial

— BRIDGE  

Official title:

A Randomized Phase III Trial of Intravesical BCG veRsus Intravesical Docetaxel and GEmcitabine Treatment in BCG Naïve High Grade Non-Muscle Invasive Bladder Cancer (BRIDGE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05538663
• Other study ID #: EA8212
• Secondary ID: U10CA180820NCI-2
• Status: Recruiting
• Phase: Phase 3
• Start date: February 7, 2023
• Est. completion date: October 2030

Study information

• Verified date: December 2023
• Source: Eastern Cooperative Oncology Group
• Contact: Max Kates, MD
• Phone: 4106140009
• Email: mkates[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study hypothesis is that BCG naïve non-muscle invasive bladder cancer (NMIBC) patients treated with intravesical Gemcitabine + Docetaxel (GEMDOCE) will result in a non-inferior event-free survival (EFS) compared to standard treatment with intravesical BCG. The purpose of this study is to test whether Gemcitabine + Docetaxel is a better or worse treatment than the usual BCG therapy approach. The primary objective of this study is to determine the event free survival (EFS) of BCG-naïve high grade non-muscle invasive bladder cancer patients treated with intravesical BCG vs Gemcitabine + Docetaxel. Secondary objectives are as follows: to compare changes in cancer-specific and bladder cancer-specific QOL from baseline to treatment between BCG-naïve high grade NMIBC patients receiving BCG and GEMDOCE, to determine the cystectomy free survival (CFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE, to determine the progression free survival (PFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE, and to determine the safety and toxicity of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE.

Description:

The primary objective of this study is to determine the event free survival (EFS) of BCG-naïve high grade non-muscle invasive bladder cancer patients treated with intravesical BCG vs Gemcitabine + Docetaxel. Secondary objectives are as follows: to compare changes in cancer-specific and bladder cancer-specific QOL from baseline to treatment between BCG-naïve high grade NMIBC patients receiving BCG and GEMDOCE, to determine the cystectomy free survival (CFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE, to determine the progression free survival (PFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE, and to determine the safety and toxicity of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 870
• Est. completion date: October 2030
• Est. primary completion date: November 1, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient must be > 18 years of age.
• Patient must have histologically confirmed high-grade non-muscle invasive urothelial carcinoma of the bladder (HgTa, HGT1, CIS, HgTa + CIS, or HGT1 + CIS stage) on transurethral resection of bladder tumor (TURBT) obtained within 90 days prior to randomization.
• Patient must have all visible papillary tumor resected by the treating urologist at the site registering the patient to this protocol prior to randomization. If the treating urologist did not perform the TURBT as outlined in Section 3.1.3, the treating urologist must perform a cystoscopy within 28 days prior to randomization to confirm the absence of visible papillary disease.
• Patient must have not received prior intravesical therapy for bladder cancer, with the exception of perioperative chemotherapy at the time of TURBT.
• Patients with high grade T1 disease must have undergone a restaging TURBT within 90 days prior to Step 1 randomization. NOTE: Patients with high grade T1 disease who undergo a restaging TURBT that shows no residual cancer in the restaging TURBT specimen are eligible.
• Patient must not have pure squamous cell carcinoma or adenocarcinoma.
• Patient must not have any component of neuroendocrine carcinoma (i.e., small cell or large cell).
• Patient must not have any component of sarcomatoid, micropapillary, or plasmacytoid variant histology.
• 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.
• Patient must have ECOG Performance Status 0-2.
• Patient may have received prior systemic gemcitabine or docetaxel use if it was for a non-bladder malignancy.
• 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 adequate organ and marrow function as defined below (these labs must be obtained = 28 days prior to randomization): Leukocytes = 3,000/mcL Leukocytes:__________ Date of Test:__________ Absolute neutrophil count (ANC) = 1,500/mcL ANC:__________ Date of Test:__________ Platelets = 70,000/mcL Platelets:__________ Date of Test:__________ Total Bilirubin = institutional upper limit of normal (ULN) Total Bilirubin:__________ Institutional ULN:_________ Date of Test:__________ AST(SGOT)/ALT(SGPT) = 3.0 × institutional ULN AST:_______ Institutional ULN:_________ Date of Test:_______ ALT: _______Institutional ULN:_________
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. 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.

Exclusion Criteria:

• Patient must not have any prior or current history of muscle-invasive (i.e., T2, T3, T4), locally advanced unresectable, or metastatic urothelial carcinoma as assessed on radiographic imaging obtained within 90 days prior to randomization. The radiographic imaging includes a CT Scan OR MRI of the abdomen/pelvis with intravenous contrast. NOTE: If a patient's renal function does not permit the administration of intravenous contrast, either a CT scan or MRI of the abdomen/pelvis without intravenous contrast is acceptable. NOTE: Patients with a history of non-invasive (Ta, Tis) upper tract urothelial carcinoma that has been definitively treated with at least one post-treatment disease assessment (i.e., either cytology, biopsy, or imaging) that demonstrates no evidence of residual disease are eligible.
• 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 randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, 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). Patient of child bearing potential? ______ (Yes or No) Date of blood test or urine study: ___________
• Patient must not expect to conceive or father children by using an accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study. In addition,patients on Arm A must continue contraception measures for six months after the last dose of GEMDOCE for patients of child-bearing potential and continue for three month after the last dose of GEMDOC for male patients with partners of child-bearing potential. All patients must not breastfeed during their time on protocol treatment.
• Patient must not have a history of severe hypersensitivity reactions to docetaxel or drugs formulated with polysorbate 80.

Related Conditions & MeSH terms

• Non-muscle-invasive Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• Gemcitabine
Intravesical once a week for 6 consecutive weeks followed by monthly instillations during maintenance for 2 years
• Docetaxel
Intravesical once a week for 6 consecutive weeks followed by monthly instillations during maintenance for 2 years
• Bacillus Calmette Guerin
intravesical once a week for 6 consecutive weeks during induction followed by weekly instillations for 3 consecutive weeks at months 3, 6, 12, 18, 24, 30, and 36 months

Locations

Country	Name	City	State
United States	Albany Medical Center	Albany	New York
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Saint Anthony's Health	Alton	Illinois
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	AnMed Health Cancer Center	Anderson	South Carolina
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado
United States	UCHealth University of Colorado Hospital	Aurora	Colorado
United States	Saint Alphonsus Medical Center-Baker City	Baker City	Oregon
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	Billings Clinic Cancer Center	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Saint Elizabeth Boardman Hospital	Boardman	Ohio
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	McFarland Clinic - Boone	Boone	Iowa
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Boulder Community Foothills Hospital	Boulder	Colorado
United States	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Rocky Mountain Cancer Centers - Centennial	Centennial	Colorado
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Saint Mary's Hospital	Centralia	Illinois
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Ralph H Johnson VA Medical Center	Charleston	South Carolina
United States	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	MD Anderson in The Woodlands	Conroe	Texas
United States	Dayton Physician LLC-Miami Valley Hospital North	Dayton	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado
United States	Rocky Mountain Cancer Centers-Rose	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	The Women's Imaging Center	Denver	Colorado
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Walter Knox Memorial Hospital	Emmett	Idaho
United States	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado
United States	Rocky Mountain Cancer Centers - Swedish	Englewood	Colorado
United States	Swedish Medical Center	Englewood	Colorado
United States	The Melanoma and Skin Cancer Institute	Englewood	Colorado
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Fairbanks Memorial Hospital	Fairbanks	Alaska
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	MUSC Health Florence Medical Center	Florence	South Carolina
United States	McFarland Clinic - Trinity Cancer Center	Fort Dodge	Iowa
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Ben Taub General Hospital	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	MD Anderson West Houston	Houston	Texas
United States	Michael E DeBakey VA Medical Center	Houston	Texas
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	McFarland Clinic - Jefferson	Jefferson	Iowa
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Monmouth Medical Center Southern Campus	Lakewood	New Jersey
United States	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado
United States	Karmanos Cancer Institute at McLaren Greater Lansing	Lansing	Michigan
United States	MD Anderson League City	League City	Texas
United States	UTMB Cancer Center at Victory Lakes	League City	Texas
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	CARTI Cancer Center	Little Rock	Arkansas
United States	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado
United States	Saint Barnabas Medical Center	Livingston	New Jersey
United States	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Los Angeles General Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	McFarland Clinic - Marshalltown	Marshalltown	Iowa
United States	Loyola University Medical Center	Maywood	Illinois
United States	Marjorie Weinberg Cancer Center at Loyola-Gottlieb	Melrose Park	Illinois
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	LSU Healthcare Network / Metairie Multi-Specialty Clinic	Metairie	Louisiana
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Community Medical Hospital	Missoula	Montana
United States	Memorial Sloan Kettering Bergen	Montvale	New Jersey
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Louisiana State University Health Science Center	New Orleans	Louisiana
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	Lake Regional Hospital	Osage Beach	Missouri
United States	Mercy Health - Paducah Medical Oncology and Hematology	Paducah	Kentucky
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Jefferson Healthcare	Port Townsend	Washington
United States	Oregon Health and Science University	Portland	Oregon
United States	Portland VA Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Reid Health	Richmond	Indiana
United States	Fox Chase Cancer Center-Rockledge	Rockledge	Pennsylvania
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Kootenai Cancer Clinic	Sandpoint	Idaho
United States	FHCC South Lake Union	Seattle	Washington
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Welch Cancer Center	Sheridan	Wyoming
United States	North Shore Medical Center	Skokie	Illinois
United States	Robert Wood Johnson University Hospital Somerset	Somerville	New Jersey
United States	Maine Medical Partners Urology	South Portland	Maine
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	MD Anderson in Sugar Land	Sugar Land	Texas
United States	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado
United States	Community Medical Center	Toms River	New Jersey
United States	Dayton Physicians LLC - Troy	Troy	Ohio
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	Saint Joseph Warren Hospital	Warren	Ohio
United States	George Washington University Medical Center	Washington	District of Columbia
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Mercy Hospital Washington	Washington	Missouri
United States	Sibley Memorial Hospital	Washington	District of Columbia
United States	Lexington Medical Center	West Columbia	South Carolina
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts
United States	Saint Elizabeth Youngstown Hospital	Youngstown	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-Free Survival	To determine the event free survival (EFS) of BCG-naïve high grade non-muscle invasive bladder cancer (NMIBC) patients treated with intravesical BCG vs GEMDOCE.	2 years
Secondary	Quality of Life FACT-G	To compare changes in cancer-specific QOL from baseline to treatment between BCG-naïve high grade NMIBC patients receiving BCG and GEMDOCE.	3 years
Secondary	Cystectomy free survival	To determine the cystectomy free survival (CFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE.	3 years
Secondary	Progression Free Survival	To determine the progression free survival (PFS) of BCG-naïve high grade NMIBC patients treated with intravesical BCG vs GEMDOCE	3 years
Secondary	Quality of Life EORTC NMIBC-24	To compare changes in bladder cancer-specific QOL from baseline to treatment between BCG-naïve high grade NMIBC patients receiving BCG and GEMDOCE.	3 years