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

Condition(s) targeted: Bladder Cancer

Intervention: cisplatin (Drug); doxorubicin hydrochloride (Drug); methotrexate (Drug); vinblastine (Drug); gene expression profiling (Procedure); neoadjuvant therapy (Procedure)

Phase: Phase 2

Status: Recruiting

Sponsored by: Kyoto University

Official(s) and/or principal investigator(s):
Osamu Ogawa, MD, PhD, Study Chair, Affiliation: Kyoto University

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.

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

Study design: Treatment, Open Label

Primary outcome: Detection of genes associated with sensitivity to the chemotherapy in tumor size reduction of original bladder tumor

Secondary outcome:

Safety

Overall survival rate

Size reduction of metastatic lesion

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.

Minimum age: 20 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

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

Osaka Red Cross Hospital, Osaka 543-8555, Japan; Recruiting
Kazuo Nishimura, MD, Phone: 81-6-6774-5111-5192

Kyoto University Hospital, Kyoto 606-8507, Japan; Recruiting
Osamu Ogawa, MD, PhD, Phone: 81-75-751-3329

National Hospital Organization - Kyoto Medical Center, Kyoto 612-0861, Japan; Recruiting
Hiroshi Okuno, MD, Phone: 81-75-641-9161

Nagoya University Hospital, Nagoya, Aichi 466-8560, Japan; Recruiting
Yasushi Yoshino, MD, Phone: 81-52-744-2985

Shiga Medical Center for Adults, Moriyama, Shiga 524-8524, Japan; Recruiting
Yuzuru Megumi, MD, Phone: 81-77-582-5031

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: July 2007
Last updated: July 23, 2008