Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Alternate Title

Surgery With or Without Chemotherapy in Treating Patients With Bladder Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	any age	NCI	SWOG-8710 CLB-8891, EST-1887, INT-0080

Objectives

I.  Compare survival of patients with locally advanced bladder cancer 
randomized to treatment with cystectomy alone vs. neoadjuvant chemotherapy 
with MVAC (methotrexate/vinblastine/doxorubicin/cisplatin) followed by 
cystectomy.

II.  Quantify the "tumor downstaging" effect of neoadjuvant MVAC.

III.  Explore the feasibility of collecting tissues for genetic/cytogenetic 
studies, and pilot the detection of nonrandom genetic/cytogenetic changes in 
these patients.

Entry Criteria

Disease Characteristics:

Histologically proven transitional cell carcinoma of the bladder

Stage T2-T4a N0 M0 with or without squamous differentiation
  Adenocarcinoma specifically excluded

Normal organ function must be documented within 6 weeks of entry by
pretreatment staging and pathologic assessment of tumor grade and depth of
invasion, including the following:
  Cystourethroscopy and bimanual exam with bladder mapping

  IVP revealing at least 1 kidney and proximal ureter free of tumor and all
  other disease potentially resectable (abdominal/pelvic CT with iv bolus
  contrast and of sufficient resolution and quality to rule out upper urinary
  tract disease may be substituted for IVP)

  Urine cytology (strongly recommended but not required)

  Absence of metastatic disease on complete physical exam, including chest
  x-ray and abdominal/pelvic CT

Mild to moderate hydronephrosis acceptable if renal function tests are
adequate (ureteral stents or percutaneous nephrostomy tubes should be
considered in cases of obstructed kidney prior to initiation of treatment)

Any nodes 2 cm or greater in diameter on CT must be demonstrated to be free of
tumor by needle biopsy

Patients must not be eligible for higher priority SWOG, ECOG, or CALGB
protocols

Prior/Concurrent Therapy:

Prior intravesical therapy allowed provided all local/systemic signs and
symptoms of treatment-related side effects have completely resolved

Biologic therapy:
  Not specified

Chemotherapy:
  Not specified

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior pelvic irradiation

Surgery:
  Not specified

Patient Characteristics:

Age:
  Any age

Performance status:
  SWOG 0 or 1 (Karnofsky 70%-100%)

Hematopoietic:
  Obtained within 14 days of registration:
    WBC at least 4,000
    Platelets at least 150,000

Hepatic:
  Obtained within 14 days of registration:
    Bilirubin within normal limits
    AST no greater than twice normal

Renal:
  Obtained within 14 days of registration:
     Creatinine no greater than 1.5 mg/dL in males and 1.2 mg/dL in females OR
     24-hour creatinine clearance at least 50 mL/min

Cardiovascular:
  No serious arrhythmias or NYHA class III/IV congestive disease on prestudy
  EKG

Other:
  Patients must be medically and psychologically capable of undergoing
     protocol treatment
  No second malignancy within 5 years except nonmelanomatous skin cancer
  No pregnant or nursing women
  Effective contraception required of fertile women

Imaging studies and physical exams for tumor measurement completed within 14
days prior to registration; screening exams other than blood/body fluid
analyses and imaging studies of nonmeasurable disease or uninvolved organs
completed within 42 days prior to registration

Expected Enrollment

298 patients will be required; the anticipated accrual rate is 6.2 patients 
per month.

Outline

Randomized study.

Arm I:  Surgery.  Cystectomy.

Arm II:  4-Drug Combination Chemotherapy followed by Surgery.  MVAC:  
Methotrexate, MTX, NSC-740; Vinblastine, VBL, NSC-49842; Doxorubicin, DOX, 
NSC-123127; Cisplatin, CDDP, NSC-119875; followed by cystectomy.

Sonpavde G, Goldman BH, Speights VO, et al.: Quality of pathologic response and surgery correlate with survival for patients with completely resected bladder cancer after neoadjuvant chemotherapy. Cancer 115 (18): 4104-9, 2009.[PUBMED Abstract]

Dotan ZA, Bajorin DF, Grossman BH, et al.: Optimal combined modality treatment improves outcome of locally advanced bladder cancer: analysis of SWOG 8710. [Abstract] J Clin Oncol 23 (Suppl 16): A-4531, 385s, 2005.

Herr HW, Faulkner JR, Grossman HB, et al.: Pathologic evaluation of radical cystectomy specimens: a cooperative group report. Cancer 100 (11): 2470-5, 2004.[PUBMED Abstract]

Herr HW, Faulkner JR, Grossman HB, et al.: Surgical factors influence bladder cancer outcomes: a cooperative group report. J Clin Oncol 22 (14): 2781-9, 2004.[PUBMED Abstract]

Grossman HB, Natale RB, Tangen CM, et al.: Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 349 (9): 859-66, 2003.[PUBMED Abstract]

Herr H, Faulkner JR, Grossman HB, et al.: Surgical variables impact bladder cancer outcomes: a cooperative group report. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1540, 2003.

Crawford D, Grossman B, Blumenstein B, et al.: SWOG 8710 (INT-0080): randomized phase III trial of neoadjuvant MVAC + cystectomy versus cystectomy alone in patients with locally advanced bladder cancer. [Abstract] J Urol 165(5 suppl): A-1069, 260, 2001.

Natale RB, Grossman HB, Blumenstein B, et al.: SWOG 8710 (INT-0080): randomised phase III trial of neoadjuvant MVAC + cystectomy versus cystectomy alone in patients with locally advanced bladder cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-3, 2a, 2001.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Ronald Natale, MD, Protocol chair(Contact information may not be current)		Ph: 213-764-0470; 800-865-0102

Eastern Cooperative Oncology Group

Donald Trump, MD, Protocol chair(Contact information may not be current)		Ph: 412-623-3205

Cancer and Leukemia Group B

Nicholas Vogelzang, MD, Protocol chair(Contact information may not be current)		Ph: 773-702-6743; 888-824-0200 Email: nvogelza@medicine.bsd.uchicago.edu

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