Bladder Cancer

EA8212 / BRIDGE



A Randomized Phase III Trial of Intravesical BCG versus Intravesical Docetaxel and Gemcitabine Treatment in BCG Non-Muscle Invasive Bladder Cancer (BRIDGE)

STATUS: Approved


This phase III trial tests whether gemcitabine and docetaxel works to shrink tumors in patients with non-muscle invasive bladder cancer. Chemotherapy drugs, such as gemcitabine and docetaxel, 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. BCG is a weakened form of the bacterium Mycobacterium bovis that does not cause disease. BCG is used in a solution to stimulate the immune system in the treatment of bladder cancer. Giving gemcitabine and docetaxel may work better in preventing bladder cancer from coming back (recurrence) compared to usual treatment with BCG.
  • 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, the treating urologist must perform a cystoscopy within 28 days prior to randomization to confirm the absence of visible papillary disease.

  • 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.

  • 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.

  • Leukocytes >= 3,000/mcL (obtained =< 28 days prior to randomization).

  • Absolute neutrophil count (ANC) >= 1,500/mcL (obtained =< 28 days prior to randomization).

  • Platelets >= 70,000/mcL (obtained =< 28 days prior to randomization).

  • Total bilirubin =< institutional upper limit of normal (ULN) (obtained =< 28 days prior to randomization).

  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT ])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) =< 3.0 x institutional ULN (obtained =< 28 days prior to randomization).

  • 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.

  • 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 computed tomography (CT) scan OR magnetic resonance imaging (MRI) of the abdomen/pelvis with intravenous contrast. * Note: If a patientโ€™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 have not received prior intravesical therapy for bladder cancer, with the exception of perioperative chemotherapy at the time of TURBT.

  • 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.

  • 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 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.

United States
AK
Fairbanks
Fairbanks Memorial Hospital
Contact: Site Public Contact
Email: Veronica.Stevenson@foundationhealth.org

AR
Ft. Smith
Mercy Hospital Fort Smith
Contact: Site Public Contact

CO
Aurora
Rocky Mountain Cancer Centers-Aurora
Contact: Site Public Contact
Email: info@westernstatesncorp.org

Boulder
Boulder Community Foothills Hospital
Contact: Site Public Contact
Email: info@westernstatesncorp.org

Rocky Mountain Cancer Centers-Boulder
Contact: Site Public Contact
Email: info@westernstatesncorp.org

Centennial
Rocky Mountain Cancer Centers - Centennial
Contact: Site Public Contact
Email: info@westernstatesncorp.org

Denver
Colorado Blood Cancer Institute
Contact: Site Public Contact
Email: info@westernstatesncorp.org

Presbyterian - Saint Lukes Medical Center - Health One
Contact: Site Public Contact
Email: info@westernstatesncorp.org

Rocky Mountain Cancer Centers-Midtown
Contact: Site Public Contact
Email: info@westernstatesncorp.org

Rocky Mountain Cancer Centers-Rose
Contact: Site Public Contact
Email: info@westernstatesncorp.org

Rose Medical Center
Contact: Site Public Contact
Email: ccrp@co-cancerresearch.org

The Women's Imaging Center
Contact: Site Public Contact
Email: info@westernstatesncorp.org

Englewood
Mountain Blue Cancer Care Center - Swedish
Contact: Site Public Contact
Email: info@westernstatesncorp.org

Rocky Mountain Cancer Centers - Swedish
Contact: Site Public Contact
Email: info@westernstatesncorp.org

Swedish Medical Center
Contact: Site Public Contact
Email: info@westernstatesncorp.org

The Melanoma and Skin Cancer Institute
Contact: Site Public Contact
Email: ryan.weight@theskincancerinstitute.com

Lakewood
Rocky Mountain Cancer Centers-Lakewood
Contact: Site Public Contact
Email: info@westernstatesncorp.org

Littleton
Rocky Mountain Cancer Centers-Littleton
Contact: Site Public Contact
Email: info@westernstatesncorp.org

Lone Tree
Rocky Mountain Cancer Centers-Sky Ridge
Contact: Site Public Contact
Email: info@westernstatesncorp.org

Thornton
Rocky Mountain Cancer Centers-Thornton
Contact: Site Public Contact
Email: info@westernstatesncorp.org

IA
Ames
Mary Greeley Medical Center
Contact: Site Public Contact

McFarland Clinic PC - Ames
Contact: Site Public Contact
Email: ksoder@mcfarlandclinic.com

Boone
McFarland Clinic PC-Boone
Contact: Site Public Contact

Fort Dodge
McFarland Clinic PC-Trinity Cancer Center
Contact: Site Public Contact

Jefferson
McFarland Clinic PC-Jefferson
Contact: Site Public Contact

Marshalltown
McFarland Clinic PC-Marshalltown
Contact: Site Public Contact

IL
Alton
Saint Anthony's Health
Contact: Site Public Contact

Mount Vernon
Good Samaritan Regional Health Center
Contact: Site Public Contact

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

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

LA
Metairie
LSU Healthcare Network / Metairie Multi-Specialty Clinic
Contact: Site Public Contact
Email: emede1@lsuhsc.edu

New Orleans
Louisiana State University Health Science Center
Contact: Site Public Contact
Email: emede1@lsuhsc.edu

MA
Boston
Brigham and Women's Hospital
Contact: Site Public Contact

MD
Baltimore
Johns Hopkins University/Sidney Kimmel Cancer Center
Contact: Site Public Contact
Email: jhcccro@jhmi.edu

MO
Ballwin
Saint Louis Cancer and Breast Institute-Ballwin
Contact: Site Public Contact

Bolivar
Central Care Cancer Center - Bolivar
Contact: Site Public Contact
Email: aroland@kccop.org

Branson
Cox Cancer Center Branson
Contact: Site Public Contact

Joplin
Freeman Health System
Contact: Site Public Contact
Email: LJCrockett@freemanhealth.com

Mercy Hospital Joplin
Contact: Site Public Contact
Email: esmeralda.carrillo@mercy.net

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

Mercy Clinic-Rolla-Cancer and Hematology
Contact: Site Public Contact

Saint Joseph
Heartland Regional Medical Center
Contact: Site Public Contact
Email: linda.schumacher@mymlc.com

Saint Louis
Mercy Hospital Saint Louis
Contact: Site Public Contact

Mercy Hospital South
Contact: Site Public Contact
Email: janet.lesko@mercy.net

Saint Louis Cancer and Breast Institute-South City
Contact: Site Public Contact

Springfield
CoxHealth South Hospital
Contact: Site Public Contact

Mercy Hospital Springfield
Contact: Site Public Contact

Washington
Mercy Hospital Washington
Contact: Site Public Contact

NJ
Basking Ridge
Memorial Sloan Kettering Basking Ridge
Contact: Site Public Contact

Middletown
Memorial Sloan Kettering Monmouth
Contact: Site Public Contact

Montvale
Memorial Sloan Kettering Bergen
Contact: Site Public Contact

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

Commack
Memorial Sloan Kettering Commack
Contact: Site Public Contact

New York
Memorial Sloan Kettering Cancer Center
Contact: Site Public Contact

Uniondale
Memorial Sloan Kettering Nassau
Contact: Site Public Contact

West Harrison
Memorial Sloan Kettering Westchester
Contact: Site Public Contact

OK
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

SC
Greenville
Prisma Health Greenville Memorial Hospital
Contact: Site Public Contact

West Columbia
Lexington Medical Center
Contact: Site Public Contact
Email: LMCIRB@lexhealth.org

TX
Galveston
University of Texas Medical Branch
Contact: Site Public Contact
Email: clinical.research@utmb.edu

League City
UTMB Cancer Center at Victory Lakes
Contact: Site Public Contact

WV
Morgantown
West Virginia University Healthcare
Contact: Site Public Contact
Email: cancertrialsinfo@hsc.wvu.edu

WY
Cheyenne
Cheyenne Regional Medical Center-West
Contact: Site Public Contact
Email: ccrp@co-cancerresearch.org

PRIMARY OBJECTIVE:
I. To determine the event free survival (EFS) of Bacillus Calmette-Guerin (BCG)- naive high grade non-muscle invasive bladder cancer (NMIBC) patients treated with intravesical BCG versus (vs) gemcitabine hydrochloride (gemcitabine) and docetaxel (GEMDOCE).

SECONDARY OBJECTIVES:
I. To compare changes in cancer-specific and bladder cancer-specific quality of life (QOL) from baseline to treatment between BCG-naive high grade NMIBC patients receiving BCG and GEMDOCE.
II. To determine the cystectomy free survival (CFS) of BCG-naive high grade NMIBC patients treated with intravesical BCG vs GEMDOCE.
III. To determine the progression free survival (PFS) of BCG-naive high grade NMIBC patients treated with intravesical BCG vs GEMDOCE.
IV. To determine the safety and toxicity of BCG-naive high grade NMIBC patients treated with intravesical BCG vs GEMDOCE.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A:
INDUCTION: Patients receive gemcitabine hydrochloride intravesically (IVES) and docetaxel IVES once a week (QW) for 6 weeks in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients with complete response (CR) or resected low grade noninvasive bladder cancer (LgTa) after induction therapy receive gemcitabine hydrochloride IVES and docetaxel IVES monthly for up to 2 years in the absence of disease progression or unacceptable toxicity.

ARM B:
INDUCTION: Patients receive BCG IVES QW for 6 weeks in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients with a CR or LgTa after induction therapy receive BCG IVES QW at 3, 6, 12, 18, 24, 30, and 36 months after the start of induction treatment in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

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.


EA8212 / BRIDGE Home Page
ECOG-ACRIN Cancer Research Group