S0353, Gemcitabine in Treating Patients With Recurrent Bladder Cancer That Has Not Responded to Previous Bacillus Calmette-Guerin

• ClinicalTrials.gov Identifier: NCT00234039
• Recruitment Status: Completed
• First Posted: October 6, 2005
• Results First Posted: December 18, 2012
• Last Update Posted: January 8, 2016
• Sponsor: Southwest Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Southwest Oncology Group

Study Description

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 may kill more tumor cells.

PURPOSE: This phase II trial is studying how well gemcitabine works in treating patients with recurrent bladder cancer that has progressed despite previous Bacillus Calmette-Guerin (BCG).

Condition or disease	Intervention/treatment	Phase
Bladder Cancer	Drug: gemcitabine hydrochloride	Phase 2

Detailed Description:

OBJECTIVES:

• Determine the 8-12 week efficacy of intravesical gemcitabine, in terms of complete response rate, in patients with recurrent superficial transitional cell carcinoma of the bladder that have progressed despite prior intravesical Bacillus Calmette-Guerin (BCG).
• Determine the recurrence-free, worsening-free, progression-free, and overall survival of patients treated with this drug.
• Evaluate the toxicity of this drug in these patients.
• Correlate, preliminarily, expression levels of genes or genetic polymorphisms involved in the gemcitabine pathway and angiogenesis with clinical toxicity, response, and relapse-free survival of patients treated with this drug.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive gemcitabine intravesically once a week for 6 weeks (weeks 1-6) in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response proceed to maintenance therapy at week 14.
• Maintenance therapy: Patients receive gemcitabine intravesically once in weeks 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 25-45 patients will be accrued for this study within 6-12 months.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 58 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Intravesical Gemcitabine in Patients With Superficial Bladder Cancer Who Have Progressed Despite Intravesical BCG
• Study Start Date: November 2006
• Actual Primary Completion Date: November 2011
• Actual Study Completion Date: April 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intravesical Gemcitabine	Drug: gemcitabine hydrochloride

Outcome Measures

Primary Outcome Measures :

1. Complete Response Rate at the End of Induction [ Time Frame: Week 8-12, then every 3 months for the first 2 years, and then every 6 months for the years 3-5 ]
   Complete Response is defined as negative cystoscopy with negative biopsy and no evidence of cancer on urine cytology at the Week 8 - 12 cystoscopy

Secondary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: 1 year ]
   Measured from the day of registration to death due to any cause. Survival is censored at date of last contact.
2. Recurrence-free Survival (RFS) [ Time Frame: 1 year ]
   Recurrence-free Survival is defined as time from registration to first instance of disease recurrence, or death due to any cause.
3. Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [ Time Frame: Patients were assessed for adverse events weekly for 6 weeks and then every 4 weeks for 40 weeks ]
   Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 120 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed superficial transitional cell carcinoma (TCC) of the bladder meeting 1 of the following stage criteria:

  • Stage T1, grade 2-3
  • Stage Tis
  • Stage Ta, grade 3-4 or multifocal (> 2 lesions)
• Must have received and failed ≥ 2 courses of intravesical Bacillus Calmette-Guerin (BCG) (one 6-week course, plus one 3-week course, or fewer weeks if BCG was discontinued due to side effects) within the past 3 years

• Recurrent disease

  • Must have had a transurethral resection of the bladder tumor (TURBT) or bladder biopsy within the past 60 days documenting tumor recurrence and tumor stage and grade

    • TURBT or biopsy must have been performed ≥ 6 weeks after the completion of BCG and/or other immunotherapy treatment (or ≥ 14 days after completion of intravesical chemotherapy treatment)
    • All visible tumor must have been resected at the time of the last biopsy
• No evidence of urethral or renal pelvis TCC by upper tract radiological imaging (e.g., intravenous pyelogram, CT urogram, or retrograde pyelogram) within the past 2 years

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer that is in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• Prior intravesical interferon alfa allowed, alone or in combination with Bacillus Calmette-Guerin (BCG)

Chemotherapy

• See Disease Characteristics
• No more than 1 course of intravesical chemotherapy (e.g., thiotepa, mitomycin, or doxorubicin) within the past year, defined as 6 or more weekly instillations, with or without monthly maintenance instillations
• No prior gemcitabine

Endocrine therapy

• Not specified

Radiotherapy

• No prior pelvic radiotherapy
• No concurrent radiotherapy to any other area of the body

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Contacts and Locations

  Hide Study Locations

Locations

United States, Arkansas

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States, 72205

United States, California

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States, 90089-9181

United States, Florida

Cancer Centers of Central Florida, PA

Leesburg, Florida, United States, 34788

United States, Hawaii

Kapiolani Medical Center at Pali Momi

Aiea, Hawaii, United States, 96701

Cancer Research Center of Hawaii

Honolulu, Hawaii, United States, 96813

OnCare Hawaii, Incorporated - Lusitana

Honolulu, Hawaii, United States, 96813

Queen's Cancer Institute at Queen's Medical Center

Honolulu, Hawaii, United States, 96813

Straub Clinic and Hospital, Incorporated

Honolulu, Hawaii, United States, 96813

Hawaii Medical Center - East

Honolulu, Hawaii, United States, 96817

OnCare Hawaii, Incorporated - Kuakini

Honolulu, Hawaii, United States, 96817

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States, 96826

Tripler Army Medical Center

Honolulu, Hawaii, United States, 96859

Maui Memorial Medical Center

Wailuku, Hawaii, United States, 96793

Pacific Cancer Institute - Maui

Wailuku, Hawaii, United States, 96793

United States, Illinois

Decatur Memorial Hospital Cancer Care Institute

Decatur, Illinois, United States, 62526

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood, Illinois, United States, 60153

Regional Cancer Center at Memorial Medical Center

Springfield, Illinois, United States, 62781-0001

United States, Indiana

St. Francis Hospital and Health Centers - Beech Grove Campus

Beech Grove, Indiana, United States, 46107

Reid Hospital & Health Care Services

Richmond, Indiana, United States, 47374

United States, Kansas

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

Kansas City, Kansas, United States, 66160-7357

Olathe Cancer Center

Olathe, Kansas, United States, 66061

United States, Louisiana

Highland Clinic

Shreveport, Louisiana, United States, 71105

Feist-Weiller Cancer Center at Louisiana State University Health Sciences

Shreveport, Louisiana, United States, 71130-3932

United States, Michigan

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States, 48109-0942

Battle Creek Health System Cancer Care Center

Battle Creek, Michigan, United States, 49017

Mecosta County Medical Center

Big Rapids, Michigan, United States, 49307

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States, 48201-1379

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, United States, 48202

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, United States, 49503

CCOP - Grand Rapids

Grand Rapids, Michigan, United States, 49503

Lacks Cancer Center at Saint Mary's Health Care

Grand Rapids, Michigan, United States, 49503

Mercy General Health Partners

Muskegon, Michigan, United States, 49443

Munson Medical Center

Traverse City, Michigan, United States, 49684

Metro Health Hospital

Wyoming, Michigan, United States, 49519

United States, Montana

CCOP - Montana Cancer Consortium

Billings, Montana, United States, 59101

Hematology-Oncology Centers of the Northern Rockies - Billings

Billings, Montana, United States, 59101

Northern Rockies Radiation Oncology Center

Billings, Montana, United States, 59101

St. Vincent Healthcare Cancer Care Services

Billings, Montana, United States, 59101

Billings Clinic - Downtown

Billings, Montana, United States, 59107-7000

St. James Healthcare Cancer Care

Butte, Montana, United States, 59701

Big Sky Oncology

Great Falls, Montana, United States, 59405-5309

Great Falls Clinic - Main Facility

Great Falls, Montana, United States, 59405

Sletten Cancer Institute at Benefis Healthcare

Great Falls, Montana, United States, 59405

Great Falls, Montana, United States, 59405

Northern Montana Hospital

Havre, Montana, United States, 59501

St. Peter's Hospital

Helena, Montana, United States, 59601

Glacier Oncology, PLLC

Kalispell, Montana, United States, 59901

Kalispell Medical Oncology at KRMC

Kalispell, Montana, United States, 59901

Kalispell Regional Medical Center

Kalispell, Montana, United States, 59901

Community Medical Center

Missoula, Montana, United States, 59801

Guardian Oncology and Center for Wellness

Missoula, Montana, United States, 59804

Montana Cancer Specialists at Montana Cancer Center

Missoula, Montana, United States, 59807-7877

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

Missoula, Montana, United States, 59807

United States, New Mexico

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States, 87131-5636

United States, New York

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, United States, 10032

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

Rochester, New York, United States, 14642

United States, North Carolina

Wayne Memorial Hospital, Incorporated

Goldsboro, North Carolina, United States, 27534

Rutherford Hospital

Rutherfordton, North Carolina, United States, 28139

United States, Ohio

McDowell Cancer Center at Akron General Medical Center

Akron, Ohio, United States, 44307

Grandview Hospital

Dayton, Ohio, United States, 45405

Good Samaritan Hospital

Dayton, Ohio, United States, 45406

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, United States, 45409

Samaritan North Cancer Care Center

Dayton, Ohio, United States, 45415

Veterans Affairs Medical Center - Dayton

Dayton, Ohio, United States, 45428

CCOP - Dayton

Dayton, Ohio, United States, 45429

Blanchard Valley Medical Associates

Findlay, Ohio, United States, 45840

Middletown Regional Hospital

Franklin, Ohio, United States, 45005-1066

Wayne Hospital

Greenville, Ohio, United States, 45331

Charles F. Kettering Memorial Hospital

Kettering, Ohio, United States, 45429

UVMC Cancer Care Center at Upper Valley Medical Center

Troy, Ohio, United States, 45373-1300

Clinton Memorial Hospital

Wilmington, Ohio, United States, 45177

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Xenia, Ohio, United States, 45385

United States, Oregon

Bay Area Hospital

Coos Bay, Oregon, United States, 97420

Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, United States, 97239-3098

United States, South Carolina

AnMed Cancer Center

Anderson, South Carolina, United States, 29621

CCOP - Upstate Carolina

Spartanburg, South Carolina, United States, 29303

Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

Spartanburg, South Carolina, United States, 29303

United States, Tennessee

U.T. Medical Center Cancer Institute

Knoxville, Tennessee, United States, 37920-6999

United States, Texas

Veterans Affairs Medical Center - San Antonio (Murphy)

San Antonio, Texas, United States, 78209

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States, 78229-3900

Cancer Therapy and Research Center

San Antonio, Texas, United States, 78229

University Hospital - San Antonio

San Antonio, Texas, United States, 78229

CCOP - Scott and White Hospital

Temple, Texas, United States, 76508

United States, Utah

Huntsman Cancer Institute at University of Utah

Salt Lake City, Utah, United States, 84112

United States, Virginia

Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County

Martinsville, Virginia, United States, 24115

United States, Washington

St. Joseph Cancer Center

Bellingham, Washington, United States, 98225

Olympic Hematology and Oncology

Bremerton, Washington, United States, 98310

Columbia Basin Hematology

Kennewick, Washington, United States, 99336

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States, 98104

Harborview Medical Center

Seattle, Washington, United States, 98104

Minor and James Medical, PLLC

Seattle, Washington, United States, 98104

Group Health Central Hospital

Seattle, Washington, United States, 98112

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Seattle, Washington, United States, 98122-4307

Polyclinic First Hill

Seattle, Washington, United States, 98122

University Cancer Center at University of Washington Medical Center

Seattle, Washington, United States, 98195-6043

Cancer Care Northwest - Spokane South

Spokane, Washington, United States, 99202

United States, Wyoming

Rocky Mountain Oncology

Casper, Wyoming, United States, 82609

Welch Cancer Center at Sheridan Memorial Hospital

Sheridan, Wyoming, United States, 82801

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

• Study Chair: Eila C. Skinner, MD; University of Southern California

More Information

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00234039 History of Changes
• Other Study ID Numbers: CDR0000446074; U10CA032102 ( U.S. NIH Grant/Contract ); S0353 ( Other Identifier: SWOG )
• First Posted: October 6, 2005
• Results First Posted: December 18, 2012
• Last Update Posted: January 8, 2016
• Last Verified: December 2015

Keywords provided by Southwest Oncology Group:

recurrent bladder cancer; stage 0 bladder cancer; stage I bladder cancer; transitional cell carcinoma of the bladder

Additional relevant MeSH terms:

Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Gemcitabine; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs