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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00445601
First received: March 7, 2007
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Bladder Cancer
Drug: gemcitabine hydrochloride
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III Blinded Study of Immediate Post TURBT Instillation of Gemcitabine Versus Saline in Patients With Newly Diagnosed or Occasionally Recurring Grade I/II Superficial Bladder Cancer

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Time to recurrence [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Measured from date of registration to date of first observation of recurrent disease subsequently confirmed by biopsy. Patients without recurrence are censored at the time of their last cystoscopy. Patients who die without any evidence of disease recurrence, will be censored at time of death.


Secondary Outcome Measures:
  • Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [ Time Frame: up to 4 weeks after Transurethral Resection of Bladder Tumor (TURBT) ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.

  • Worsening-free survival [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Measured from date of registration to date of first observation of subsequently confirmed recurrent disease, progression, start of systemic chemotherapy, radiation or cystectomy, or death due to any cause. Patients who experience none of these events will be censored at date of last disease assessment.

  • Sensitivity and specificity of BTA Stat test the NMP-22 Bladder Chek alone and in combination [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Evaluate whether performing a combination of molecular/cytologic diagnostic marker tests including NMP-22 Bladder Chek and BTA Stat every three months can predict recurrence as accurately as cystoscopy alone. BTA Stat and NMP-22 Bladder Chek will each be performed prior to the TURBT of the index tumor and with each surveillance cystoscopy for 2 years, or until first histologically confirmed recurrence (whichever is sooner).


Enrollment: 371
Study Start Date: September 2007
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive intravesical gemcitabine hydrochloride over 1 hour.
Drug: gemcitabine hydrochloride
Given intravesically
Placebo Comparator: Arm II
Patients receive intravesical placebo over 1 hour.
Other: placebo
Given intravesically

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00445601

  Show 70 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Edward M. Messing, MD, FACS James P. Wilmot Cancer Center
Study Chair: Deepak M. Sahasrabudhe, MD James P. Wilmot Cancer Center
Study Chair: Theresa M. Koppie, MD Oregon Health and Science University
Study Chair: David P. Wood, MD Beaumont Physician Partners
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00445601     History of Changes
Other Study ID Numbers: CDR0000534235, S0337, U10CA032102
Study First Received: March 7, 2007
Last Updated: February 18, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:
transitional cell carcinoma of the bladder
stage 0 bladder cancer
stage I bladder cancer
recurrent bladder cancer

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
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 01, 2014