S0219, Combination Chemotherapy Followed By Observation or Surgery in Patients With Stage II or Stage III Cancer of the Urothelium

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00045630
First received: September 6, 2002
Last updated: April 16, 2013
Last verified: April 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells and decrease the need for surgery.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by observation or surgery to remove the bladder (cystectomy) in treating patients who have stage II or stage III cancer of the urothelium.


Condition Intervention Phase
Bladder Cancer
Transitional Cell Cancer of the Renal Pelvis and Ureter
Urethral Cancer
Drug: carboplatin
Drug: gemcitabine
Drug: paclitaxel
Procedure: surgery
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Sequential Approach to the Treatment of Muscle Invasive, Non-Metastatic Urothelial Carcinoma of the Bladder: A Phase II Trial of Neoadjuvant Gemcitabine, Paclitaxel and Carboplatin With Molecular Correlates

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Pathologic Complete Response Rate by Transurethral Resection of Bladder Tumor (TURBT) and Imaging Studies After Chemotherapy [ Time Frame: up to 12 weeks after registration (assessed within 8 weeks after completion of 3 cycles of chemotherapy ) ] [ Designated as safety issue: No ]
    Pathologic complete response (CR) is defined as absence of viable tumor in the TURBT specimen. Stable/No Response is defined as at least some disease evaluation tests were done (same tests as baseline) and status does not qualify for CR or Progression. Progression is defined as one or more of the following must occur: unequivocal progression of disease in the opinion of the treating physician. Appearance of any new lesion/site. Death due to disease without documented progression or symptomatic deterioration.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: 0-2 years ] [ Designated as safety issue: No ]
    Overall survival is defined from the date of registration to date of death from any cause

  • 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 at weeks 1, 2, 4, 5, 7, 8, and following surgery ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.


Enrollment: 77
Study Start Date: January 2003
Study Completion Date: December 2011
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gemcitabine, Paclitaxel, Carboplatin
Gemcitabine, Paclitaxel, Carboplatin followed by surgery
Drug: carboplatin Drug: gemcitabine
Other Name: gemcitabine hydrochloride
Drug: paclitaxel
Other Name: Taxol
Procedure: surgery

Detailed Description:

OBJECTIVES:

  • Determine the pathologic complete response of patients with stage II or III transitional cell cancer of the urothelium treated with neoadjuvant gemcitabine, paclitaxel, and carboplatin followed by observation or immediate cystectomy.
  • Determine, preliminarily, if molecular markers predict response, survival, and tumor recurrence in patients treated with these regimens.
  • Determine recurrence rates and cystectomy-free survival of patients who choose observation after an initial response to neoadjuvant chemotherapy.
  • Compare the survival of patients treated with neoadjuvant chemotherapy followed by cystectomy vs observation.
  • Determine the feasibility, tolerability, and toxicity of these regimens in these patients.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine IV over 30 minutes and paclitaxel IV over 30 minutes on days 1 and 8 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Within 4-8 weeks after completion of neoadjuvant chemotherapy, patients undergo a third transurethral resection of bladder tumor.

Patients with T0 disease after neoadjuvant chemotherapy may choose to undergo observation. These patients undergo cystoscopies with biopsies every 3 months for 1 year, every 4 months for 1 year, and then every 6 months until disease progression.

Patients with T1 disease or greater after neoadjuvant chemotherapy undergo immediate cystectomy. Patients with T0 disease may also choose this option. Patients undergoing immediate cystectomy are followed every 6 months for 2 years and then annually for 3 years.

PROJECTED ACCRUAL: A total of 95 patients will be accrued for this study within 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed muscle-invasive (T2-T4a), node-negative (N0) urothelial transitional cell cancer (TCC) of the bladder
  • Focal squamous and/or adenocarcinoma differentiation, defined as ≤ 10% of tumor volume allowed
  • The following diagnoses are not allowed:

    • Small cell carcinoma
    • Sarcomatoid components
  • Disease diagnosed with an initial transurethral resection of bladder tumor (TURBT) and a second TURBT performed within 8 weeks of first with attempt to remove all tumor present

    • Residual disease after second TURBT allowed
    • No more than 14-56 days after second TURBT
  • No metastatic disease by chest x-ray and CT scan or MRI of the abdomen and pelvis
  • Fresh tumor tissue, paraffin tumor tissue, unstained slides, or cell block specimen from one or both TURBTs available

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • White blood cell count (WBC) at least 3,500/mm^3
  • Absolute granulocyte count at least 1,500/mm^3
  • Platelet count at least lower limit of normal

Hepatic

  • Bilirubin no greater than 1.5 mg/dL
  • Aspartate aminotransferase (SGOT) no greater than 2 times upper limit of normal

Renal

  • Creatinine no greater than 2.0 mg/dL AND/OR
  • Creatinine clearance at least 60 mL/min

Other

  • No prohibitive medical risk that would preclude radical cystectomy
  • No other serious concurrent systemic disorder that would preclude study compliance
  • No other malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, adequately treated stage I or II cancer in complete remission, or any other cancer for which patient has been disease-free for 5 years
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Prior intravesical immunotherapy allowed

Chemotherapy

  • No prior systemic chemotherapy for TCC of the urothelium
  • Prior intravesical chemotherapy allowed

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy for TCC of the urothelium
  • No concurrent radiotherapy

Surgery

  • See Disease Characteristics
  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: NCT00045630

  Show 128 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Primo N. Lara, MD University of California, Davis
  More Information

Additional Information:
Publications:
Lara PN, Goldman B, De Vere White R, et al.: A sequential treatment approach to muscle-invasive urothelial cancer: A phase II Southwest Oncology Group trial (S0219) of neoadjuvant paclitaxel, carboplatin, and gemcitabine (PCG). [Abstract] J Clin Oncol 26 (Suppl 15): A-5022, 2008.

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00045630     History of Changes
Obsolete Identifiers: NCT00191217
Other Study ID Numbers: CDR0000256921, S0219, U10CA032102
Study First Received: September 6, 2002
Results First Received: November 15, 2012
Last Updated: April 16, 2013
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
anterior urethral cancer
localized transitional cell cancer of the renal pelvis and ureter
posterior urethral cancer
stage II bladder cancer
stage III bladder cancer
transitional cell carcinoma of the bladder
urethral cancer associated with invasive bladder cancer
regional transitional cell cancer of the renal pelvis and ureter

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Kidney Neoplasms
Ureteral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Diseases
Ureteral Diseases
Gemcitabine
Carboplatin
Paclitaxel
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

ClinicalTrials.gov processed this record on September 18, 2014