Dose Dense MVAC for Muscle Invasive Bladder Cancer
Condition: Muscle Invasive Bladder Cancer; High Risk Urothelial Carcinoma of the Upper Urinary Tracts
MeSH terms: Carcinoma; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Kidney Neoplasms; Ureteral Neoplasms
Intervention: single arm dose dense MVAC
Intervention description: standard doses of methotrexate, vinblastine, adriamycin, and cisplatin given every 14 days.
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin; Methotrexate; Vinblastine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: bladder; cancer; invasive

Summary:

      Standard treatment for early stage bladder cancer is chemotherapy with methotrexate (M),
      vinblastine (V), adriamycin (A), and cisplatin (C) followed by surgical removal of any
      remaining cancer and the bladder with the intent of cure. The M V chemotherapy is usually
      given every 14 days with the AC given along each 28 days. This study looks at giving the same
      drugs at the same doses closer together, all drugs every 14 days, with the support of growth
      factor medication to promote growth of the white blood cells and platelets and allow
      chemotherapy to be finished sooner and surgery to be done sooner.
    

Eligibility criteria:

        Inclusion Criteria:

          -  histologically confirmed urothelial carcinoma of bladder, ureter, or renal pelvis.
             T2-T4 and muscle invasion must be established by TURBT. Upper tract must be high
             grade. N0-N1 are eligible.

          -  candidate for radical cystectomy, nephroureterectomy, or segmental ureterectomy with
             goal of cure.

             ->/= 18 years old

          -  ECOG performance status 0-1.

          -  Adequate marrow and organ function.

          -  May enter on therapeutic anticoagulation if it can be safely held during perioperative
             period.

          -  No women of childbearing potential, pregnant or breastfeeding.

          -  LVEF >/= 50 %

          -  Patients with history of other non-urothelial malignancies may enroll if: 1)no
             evidence of distant disease w/in last year. 2)No anticancer treatment for >/= 1 year
             other than adjuvant treatment or treatment for secondary prevention. 3) Less than 360
             mg/m2 lifetime dose of adriamycin.

          -  ability to understand and willingness to sign written informed consent and HIPAA.

        Exclusion Criteria:

          -  Intravesicular therapy w/in 4 weeks of study entry or those who have not recovered
             from adverse effects of such agents administered more than 4 weeks earlier.

          -  Patients may not be receiving any investigational agents within 4 weeks of study
             entry.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to Methotrexate, Vinblastine, Adriamycin or Cisplatin or other agents used
             in the study.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study due to the potential for teratogenic or
             abortifacient effects of cytotoxic chemotherapy.

          -  Known HIV-positive patients on combination antiretroviral therapy are ineligible
             because of the potential for pharmacokinetic interactions with cytotoxic chemotherapy.
             In addition, these patients are at increased risk of lethal infections when treated
             with marrow-suppressive therapy.

             -. Patients who have undergone prior pelvic radiation are excluded due to risk of life
             threatening myelosuppression.

          -  Patients who have received any previous systemic chemotherapy or radiation therapy for
             urothelial carcinoma or cytotoxic chemotherapy for another malignancy within 1 year of
             study entry are ineligible.