S0337, Gemcitabine After Surgery in Treating Patients With Newly Diagnosed or Recurrent Bladder Cancer

NCT ID: NCT00445601

Last Updated: 2020-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 406 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2017-06-30

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving gemcitabine directly into the bladder after surgery may kill more tumor cells. It is not yet known whether giving gemcitabine directly into the bladder is more effective than a placebo in treating bladder cancer.

PURPOSE: This randomized phase III trial is studying gemcitabine to see how well it works when given directly into the bladder compared with a placebo after surgery in treating patients with newly diagnosed or recurrent bladder cancer.

Detailed Description

OBJECTIVES:

Primary

• Compare the efficacy of a single intravesical instillation of gemcitabine hydrochloride vs placebo immediately after transurethral resection of the bladder tumor (TURBT) in preventing recurrence at 2 years in patients with grade 1 or 2 superficial transitional cell cancer of the bladder.

Secondary

• Compare whether a single instillation of intravesical gemcitabine hydrochloride can improve the time to progression to muscle invasive disease vs placebo in these patients.
• Compare the qualitative and quantitative toxicities of these regimens in these patients.
• Compare whether treatment with post-TURBT intravesical instillation of gemcitabine vs placebo results in reduced long-term morbidity in patients, as defined by requirement for fewer TURBTs, courses of traditional intravesical therapies, and surveillance cystoscopies over 4 years.

Tertiary

• Assess whether performing a combination of molecular and/or cytologic diagnostic marker tests, including NMP-22 Bladder Chek and BTA Stat every 3 months, can predict recurrence as accurately as cystoscopy alone in these patients.

OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to disease status (first occurrence vs recurrent disease) and number of tumor sites (1 vs ≥ 2). Patients are randomized to 1 of 2 treatment arms.

All patients undergo transurethral resection of the bladder tumor. Within 3 hours, patients receive intravesical therapy according to their randomized arm.

• Arm I: Patients receive intravesical gemcitabine hydrochloride over 1 hour.
• Arm II: Patients receive intravesical placebo over 1 hour. Urine is collected at baseline and then every 3 months for 2 years for research studies including the NMP-22 Bladder Chek and BTA Stat test.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 340 patients will be accrued for this study.

Conditions

Bladder Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Arm I

Patients receive intravesical gemcitabine hydrochloride over 1 hour.

Group Type: EXPERIMENTAL

gemcitabine hydrochloride

Intervention Type: DRUG

Given intravesically

Arm II

Patients receive intravesical placebo over 1 hour.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Given intravesically

Interventions

gemcitabine hydrochloride

Given intravesically

Intervention Type: DRUG

placebo

Given intravesically

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of newly diagnosed or recurrent transitional cell bladder cancer meeting the following criteria:

• Ta or T1 primary tumor
• Grade 1 or 2 disease
• No more than 2 recurrences (except for index tumor) within the 18 months prior to the index tumor's transurethral resection of the bladder tumor (TURBT)

• Index tumor post-TURBT must meet the following criteria:

• Ta or T1 tumor without any prior tumor in situ, grade 3 (high grade) disease within 2 years prior to index tumor TURBT, or invasion of the muscularis propria (stage ≥ T2)
• Grade 1 or 2 disease (similar to papillary urothelial neoplasm of low malignant potential and low-grade bladder cancer)
• Not a candidate for a therapy other than TURBT (e.g., a series of instillations of intravesical immunotherapy [e.g., BCG] or intravesical chemotherapy, or cystectomy or partial cystectomy)
• Negative upper tract imaging studies within 1 year (365 days) prior to study entry

• Imaging studies may be performed after registration provided it is done prior to TURBT on the day of treatment
• No urothelial cancer of the prostate or more distal urethra (or urethra at all in women) as assessed by endoscopy
• Must have a negative urine culture (less than or equal to 10,000 col/mL, mixed flora-likely contamination) OR negative urine analysis for infection AND negative nitrates on reagent strip, ≤ 10 white blood cell count (WBC)/high-power field, and no rods or organisms on examination of spun urine sediment OR an automated or visual reagent strip urinalysis that is negative for leukocytes and nitrates within the past 28 days
• TURBT planned within the next 28 days and planned treatment within 3 hours after TURBT

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other prior malignancy except for any of the following:

• Adequately treated basal cell or squamous cell skin cancer
• In situ cervical cancer
• Adequately treated stage I or II cancer from which patient is in complete remission
• Any other cancer from which patient has been disease-free for 3 years

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 145 days since prior intravesical therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Edward M. Messing, MD, FACS

Role: STUDY_CHAIR

James P. Wilmot Cancer Center

Deepak M. Sahasrabudhe, MD

Role: STUDY_CHAIR

James P. Wilmot Cancer Center

Theresa M. Koppie, MD

Role: STUDY_CHAIR

Oregon Health and Science University

David P. Wood, MD

Role: STUDY_CHAIR

Beaumont Physician Partners

Locations

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center

Los Angeles, California, United States

University of California Davis Cancer Center

Sacramento, California, United States

University of Colorado Cancer Center at UC Health Sciences Center

Aurora, Colorado, United States

Urology Center of Colorado

Denver, Colorado, United States

Veterans Affairs Medical Center - Denver

Denver, Colorado, United States

St. Joseph Regional Medical Center

Lewiston, Idaho, United States

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood, Illinois, United States

St. Rose Ambulatory and Surgery Center

Great Bend, Kansas, United States

Hays Medical Center

Hays, Kansas, United States

Hutchinson Hospital Corporation

Hutchinson, Kansas, United States

Kansas City Cancer Centers - West

Kansas City, Kansas, United States

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Kansas City, Kansas, United States

Kansas City Cancer Centers - Southwest

Overland Park, Kansas, United States

Mount Carmel Regional Cancer Center

Pittsburg, Kansas, United States

Tammy Walker Cancer Center at Salina Regional Health Center

Salina, Kansas, United States

Kansas City Cancer Center - Shawnee Mission

Shawnee Mission, Kansas, United States

St. Francis Comprehensive Cancer Center

Topeka, Kansas, United States

Feist-Weiller Cancer Center at Louisiana State University Health Sciences

Shreveport, Louisiana, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, United States

William Beaumont Hospital - Royal Oak Campus

Royal Oak, Michigan, United States

Truman Medical Center - Hospital Hill

Kansas City, Missouri, United States

Veterans Affairs Medical Center - Kansas City

Kansas City, Missouri, United States

Kansas City Cancer Centers - South

Kansas City, Missouri, United States

Kansas City Cancer Centers - North

Kansas City, Missouri, United States

Kansas City Cancer Centers - East

Lee's Summit, Missouri, United States

CCOP - Montana Cancer Consortium

Billings, Montana, United States

St. Vincent Healthcare Cancer Care Services

Billings, Montana, United States

Hematology-Oncology Centers of the Northern Rockies - Billings

Billings, Montana, United States

Billings Clinic - Downtown

Billings, Montana, United States

Bozeman Deaconess Cancer Center

Bozeman, Montana, United States

St. James Healthcare Cancer Care

Butte, Montana, United States

Great Falls Clinic - Main Facility

Great Falls, Montana, United States

Sletten Cancer Institute at Benefis Healthcare

Great Falls, Montana, United States

Northern Montana Hospital

Havre, Montana, United States

St. Peter's Hospital

Helena, Montana, United States

Glacier Oncology, PLLC

Kalispell, Montana, United States

Kalispell Medical Oncology at KRMC

Kalispell, Montana, United States

Kalispell Regional Medical Center

Kalispell, Montana, United States

Montana Cancer Specialists at Montana Cancer Center

Missoula, Montana, United States

Montana Cancer Center at St. Patrick Hospital and Health Sciences Center

Missoula, Montana, United States

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, United States

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States

Bay Area Hospital

Coos Bay, Oregon, United States

Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, United States

Brooke Army Medical Center

Fort Sam Houston, Texas, United States

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

Baylor University Medical Center - Houston

Houston, Texas, United States

Methodist Hospital

Houston, Texas, United States

Veterans Affairs Medical Center - Houston

Houston, Texas, United States

Wilford Hall Medical Center

Lackland Air Force Base, Texas, United States

Veterans Affairs Medical Center - San Antonio (Murphy)

San Antonio, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Cancer Therapy and Research Center

San Antonio, Texas, United States

University Hospital - San Antonio

San Antonio, Texas, United States

Overlake Cancer Center at Overlake Hospital Medical Center

Bellevue, Washington, United States

Providence Centralia Hospital

Centralia, Washington, United States

Providence Regional Cancer Partnership

Everett, Washington, United States

St. Francis Hospital

Federal Way, Washington, United States

Providence St. Peter Hospital Regional Cancer Center

Olympia, Washington, United States

Good Samaritan Cancer Center

Puyallup, Washington, United States

Franciscan Cancer Center at St. Joseph Medical Center

Tacoma, Washington, United States

Allenmore Hospital

Tacoma, Washington, United States

CCOP - Northwest

Tacoma, Washington, United States

MultiCare Regional Cancer Center at Tacoma General Hospital

Tacoma, Washington, United States

Madigan Army Medical Center - Tacoma

Tacoma, Washington, United States

St. Clare Hospital

Tacoma, Washington, United States

Countries

United States

References

Corsi NJ, Messing EM, Sood A, Keeley J, Bronkema C, Rakic N, Jamil M, Dalela D, Arora S, Piontkowski AJ, Majdalany SE, Butaney M, Rakic I, Li P, Menon M, Rogers CG, Abdollah F. Risk-Based Assessment Of the Impact Of Intravesical Therapy on Recurrence-Free Survival Rate Following Resection of Suspected Low-grade, Non-muscle-invasive Bladder Cancer (NMIBC): A Southwest Oncology Groups (SWOG) S0337 Posthoc Analysis. Clin Genitourin Cancer. 2022 Dec;20(6):e498-e505. doi: 10.1016/j.clgc.2022.06.015. Epub 2022 Jun 25.

Reference Type: DERIVED

PMID: 35871040 (View on PubMed)

Messing EM, Tangen CM, Lerner SP, Sahasrabudhe DM, Koppie TM, Wood DP Jr, Mack PC, Svatek RS, Evans CP, Hafez KS, Culkin DJ, Brand TC, Karsh LI, Holzbeierlein JM, Wilson SS, Wu G, Plets M, Vogelzang NJ, Thompson IM Jr. Effect of Intravesical Instillation of Gemcitabine vs Saline Immediately Following Resection of Suspected Low-Grade Non-Muscle-Invasive Bladder Cancer on Tumor Recurrence: SWOG S0337 Randomized Clinical Trial. JAMA. 2018 May 8;319(18):1880-1888. doi: 10.1001/jama.2018.4657.

Reference Type: DERIVED

PMID: 29801011 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Related Links

https://nctn-data-archive.nci.nih.gov/

Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Other Identifiers

S0337

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000534235

Identifier Type: -

Identifier Source: org_study_id