S1314, Co-expression Extrapolation (COXEN) Program to Predict Chemotherapy Response in Patients With Bladder Cancer
Condition: Bladder Cancer
MeSH terms: Urinary Bladder Neoplasms
Intervention: Gemcitabine; Cisplatin; Methotrexate; Vinblastine; Doxorubicin; Filgrastim
Intervention description: Gemcitabine, 1000 mg/m2, IV (in the vein) on Days 1 and 8 of each 21 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.; Cisplatin, 70 mg/m2, IV (in the vein) on Day 1 of each 21 day cycle (or Day 1 or 2 of each 14 day cycle).
Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.; Methotrexate, 30 mg/m2, IV (in the vein) on Days 1 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.; Vinblastine, 3 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.; Doxorubicin, 30 mg/m2, IV (in the vein) on Days 1 or 2 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.; Filgrastim, 5 mcg/kg, SubQ/IV (in the vein) on Days 3-7 of each 14 day cycle. Number of Cycles: 4 cycles or until progression or unacceptable toxicity develops.
Intervention MeSH terms: Gemcitabine; Doxorubicin; Methotrexate; Vinblastine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 237.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bladder Cancer; Neoadjuvant Chemotherapy; Coexpression Extrapolation; COXEN; S1314; SWOG

Summary:

      The primary focus of this study is to see if looking at tumor biomarkers using a program
      called coexpression extrapolation or "COXEN" may predict a patient's response to chemotherapy
      before surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically proven bladder cancer (pure small cell carcinoma, pure adenocarcinoma,
             and pure squamous cell carcinoma histologies are excluded).

          -  Stage cT2-T4a N0 M0 disease.

          -  Documented muscle invasive disease with at least one of the following: disease
             measuring at least 10 mm on cross-sectional imaging OR the presence of
             tumor-associated hydronephrosis.

          -  Staging scans with abdominal/pelvic CT or MRI scan and CT scan or x-ray of the chest
             within 56 days prior to registration. If alkaline phosphatase is above the treating
             institution's upper limit of normal (ULN), presence of suspicious bone pain, or if
             other clinical suspicion, a whole body bone scan is required within 56 days prior to
             registration.

          -  Performance status = 0 or 1

          -  18 years of age or older

          -  Must have tumor tissue from transurethral resection of the bladder tumor (TURBT)
             available for submission that is sufficient for COXEN testing and must agree to
             submission of 20 (10 micron) slides plus 2 (5 micron) slides from the start and end of
             the 20 slides for a total of 22 unstained slides.

          -  Must agree to collection of tissue (if residual disease is present), urine, and whole
             blood.

          -  Must agree to participate in the translational medicine studies outlined in the
             protocol

        Exclusion Criteria:

          -  Prior systemic cytotoxic chemotherapy or systemic anthracycline

          -  Peripheral neuropathy >/= Grade 2

          -  Class III/IV heart failure or known left ventricular ejection fraction (LVEF) < 50%

          -  Clinically relevant hearing impairment > Grade 2

          -  Renal function, calculated creatinine clearance < 60 mL/min

          -  Hepatic function, total bilirubin > 1.5 x institutional upper limit of normal (IULN)
             (or > 2.5 x IULN with Gilbert's disease); AST & ALT > 2 X IULN

          -  Hematologic function, absolute neutrophil count (ANC) < 1,500/mcL, hemoglobin < 9
             g/dL, and platelets < 100,000/mcL

          -  Hypersensitivity to cisplatin, gemcitabine, doxorubicin, vinblastine, methotrexate, or
             filgrastim/pegfilgrastim

          -  Incidence of or uncontrolled medical illness (e.g. active cardiac symptoms, active
             systemic infection, etc.)

          -  Pregnant or nursing females

          -  No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
             Stage I or II cancer from which the patient is currently in complete remission, or any
             other cancer from which the patient has been disease free for five years. However,
             patients with localized prostate cancer who are being followed by an active
             surveillance program are eligible.