Gene Expression Profiling in Patients With Invasive Bladder Cancer Receiving Methotrexate, Vinblastine, Doxorubicin, and Cisplatin

Phase II Clinical Trial Concerning Gene Expression Profiling to Predict the Chemosensitivity of Invasive Bladder Cancer

RATIONALE: Drugs used in chemotherapy, such as methotrexate, vinblastine, doxorubicin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Evaluating blood or tissue samples from patients with cancer may help doctors learn more about changes that occur in DNA, identify biomarkers related to cancer, and predict how well patients will respond to combination chemotherapy.

PURPOSE: This phase II trial is studying gene expression profiling to see how well it works in predicting response to treatment in patients with invasive bladder cancer receiving methotrexate, vinblastine, doxorubicin, and cisplatin.

Study Overview

• Status: Terminated
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: methotrexate; Procedure: neoadjuvant therapy; Drug: cisplatin; Drug: doxorubicin hydrochloride; Drug: vinblastine; Genetic: gene expression profiling

Detailed Description

OBJECTIVES:

Primary

• Analyze the correlation between gene expression profile and the effect of chemotherapy and detect the significant cluster of genes useful to predict chemosensitivity.
• Confirm the reduction in original tumor size in patients with invasive bladder cancer treated with methotrexate, vinblastine, doxorubicin hydrochloride, and cisplatin.

Secondary

• Determine the safety of this regimen in these patients.
• Determine the overall survival rate in patients treated with this regimen.
• Assess the reduction in size of metastatic lesions in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive methotrexate on days 1, 15, and 22, vinblastine on days 2, 15, and 22, doxorubicin hydrochloride and cisplatin on day 2. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patient samples will be collected for gene expression profiling.

After completion of study treatment, patients are followed for 3 years.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Kyoto, Japan, 612-0861
    • National Hospital Organization - Kyoto Medical Center
  • Osaka, Japan, 543-8555
    • Osaka Red Cross Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital
  • Shiga
    • Moriyama, Shiga, Japan, 524-8524
      • Shiga Medical Center for Adults

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of invasive bladder cancer
• Must be confirmed by chest and abdominal CT scan OR pelvic MRI scan and transurethral biopsy (with definitive muscle invasion > T2) within 4 weeks prior to registration

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• WBC ≥ 3,000/mm^3
• Neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Total bilirubin ≤ 1.5 mg/dL
• Serum creatinine ≤ 1.5 mg/dL
• AST and ALT ≤ 2.5 x upper limit of normal
• Not pregnant
• No liver cirrhosis
• No ischemic cardiovascular disease or arrhythmia for which treatment is necessary
• No cardiac infarction within the past 6 months
• No interstitial pneumonia, pulmonary fibrosis, or any other diseases by which oxygen inhalation therapy is needed
• No active cancerous lesion other than upper urinary tract tumor
• No high fever or any other infectious symptom
• No uncontrolled hypertension or diabetes mellitus

PRIOR CONCURRENT THERAPY:

• No prior systemic chemotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Detection of genes associated with sensitivity to the chemotherapy in tumor size reduction of original bladder tumor

Secondary Outcome Measures

Outcome Measure
Safety
Overall survival rate
Size reduction of metastatic lesion

Collaborators and Investigators

• Sponsor: Kyoto University
• Investigators: Study Chair: Osamu Ogawa, MD, PhD, Kyoto University

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: August 14, 2007
• First Submitted That Met QC Criteria: August 14, 2007
• First Posted (Estimate): August 15, 2007

Study Record Updates

• Last Update Posted (Estimate): July 10, 2013
• Last Update Submitted That Met QC Criteria: July 9, 2013
• Last Verified: March 1, 2008

More Information

Terms related to this study

• Keywords: stage III bladder cancer; recurrent bladder cancer; stage IV bladder cancer; stage II bladder cancer
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Antibiotics, Antineoplastic; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vinblastine
• Other Study ID Numbers: TRIC-UHA-GU-03-01; CDR0000561303 (Registry Identifier: PDQ (Physician Data Query))