Combination Chemotherapy Followed By Observation or Surgery in Treating Patients With Stage II or Stage III Cancer of the Urothelium - Full Text View

Sponsor:	Southwest Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00045630

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 hydrochloride Drug: paclitaxel Procedure: conventional surgery Procedure: neoadjuvant therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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:

Genetics Home Reference related topics: bladder cancer

MedlinePlus related topics: Bladder Cancer Cancer Surgery

Drug Information available for: Paclitaxel Carboplatin Gemcitabine Gemcitabine hydrochloride

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Pathologic complete response rate by transurethral resection of bladder tumor (TURBT) and imaging studies after chemotherapy [ Designated as safety issue: No ]

Estimated Enrollment:	95
Study Start Date:	January 2003
Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

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

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
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00045630

Show 128 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Primo N. Lara, MD

University of California, Davis

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Devere White RW, Lara PN, Goldman B, Tangen CM, Smith DC, Wood DP, Hussain MH, Crawford ED. A Sequential Treatment Approach to Myoinvasive Urothelial Cancer: A Phase II Southwest Oncology Group Trial (S0219). J Urol. 2009 Apr 15; [Epub ahead of print]

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.

Study ID Numbers:	CDR0000256921, SWOG-S0219
Study First Received:	September 6, 2002
Last Updated:	April 21, 2009
ClinicalTrials.gov Identifier:	NCT00045630 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Ureteral Diseases
Urogenital Neoplasms
Urologic Neoplasms
Carcinoma, Transitional Cell
Neoplasms by Site
Urologic Diseases
Kidney Neoplasms
Therapeutic Uses

Urethral Diseases
Kidney Diseases
Gemcitabine
Neoplasms by Histologic Type
Mitosis Modulators
Urinary Bladder Diseases
Urinary Bladder Neoplasms
Enzyme Inhibitors
Antimitotic Agents
Carboplatin
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Carcinoma
Neoplasms

ClinicalTrials.gov processed this record on November 27, 2009