Chemotherapy Before Surgery in Treating Patients With High Grade Upper Urinary Tract Cancer
Condition: High Grade Upper Tract Urothelial Carcinoma
MeSH terms: Carcinoma; Carcinoma, Transitional Cell
Intervention: Methotrexate; Vinblastine; Doxorubicin; Cisplatin; Gemcitabine; Carboplatin; Pegfilgrastim; Nephroureterectomy
Intervention description: Given IV; Given IV; Given IV; Given IV; Given IV; Given IV; Administered subcutaneously; Undergo nephroureterectomy and lymph node dissection
Intervention MeSH terms: Cisplatin; Carboplatin; Gemcitabine; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vinblastine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: carcinoma; drug therapy; nephroureterectomy; urinary tract; urothelium

Summary:

      This phase II trial studies how well giving chemotherapy before surgery works in treating
      patients with aggressive upper urinary tract cancer. Drugs used in chemotherapy, such as
      methotrexate, vinblastine, doxorubicin hydrochloride, cisplatin, gemcitabine hydrochloride,
      and carboplatin, work in different ways to stop the growth of tumor cells, either by killing
      the cells, by stopping them from dividing, or by stopping them from spreading. Removing the
      affected upper urinary tract by surgery is the recommended treatment for upper urinary tract
      cancer, but can cause loss of kidney function and prevent patients from being able to receive
      chemotherapy after surgery. Giving chemotherapy before surgery, when the kidneys are working
      at their maximum, may allow less tissue to be removed during surgery and may be more
      effective in treating patients with high grade upper urinary tract cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have high grade upper tract urothelial carcinoma proven by one of the
             following:

               -  Biopsy;

               -  Urinary cytology with a 3-dimensional upper urinary tract mass on cross-sectional
                  imaging; or

               -  Urinary cytology and a mass visualized during upper urinary tract endoscopy

          -  Patients must have a creatinine clearance >= 30 ml/min as determined by
             Cockcroft-Gault calculation or 24-hour urine creatinine clearance measurement within
             28 days of registration to be eligible for the study

          -  Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Patients must have a left ventricular ejection fraction (LVEF) >= 50% by (either
             multigated acquisition [MUGA] or 2-dimensional [2-D] echocardiogram) within 28 days of
             registration

          -  Absolute neutrophil count (ANC) >= 1500/mm^3

          -  Platelets >= 100,000/mm^3

          -  Hemoglobin (HgB) >= 9

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             < 2 X institutional upper limit of normal (ULN)

          -  Bilirubin within institutional normal limits (or < 2.5 X the ULN for patients with
             Gilbert's disease)

          -  Patients with concomitant primaries of the bladder/urethra are allowed, as long as
             these sites are surgically resected and non-invasive cancers (< cT1N0)

          -  Patients may have a history of resectable urothelial cancer (including neoadjuvant
             chemotherapy) as long as patients meet one of the following:

               -  pT0, Tis, or T1N0 and have no evidence of disease (NED) for more than 2 years
                  from surgery or chemotherapy;

               -  pT2-3aN0 and NED for more than 3 years from surgery or chemotherapy; or

               -  > pT3b, or N+ and NED for more than 5 years from surgery or chemotherapy

          -  Women of childbearing potential and sexually active males must use an accepted and
             effective method of contraception or to abstain from sexual intercourse for the
             duration of their participation in the study

        Exclusion Criteria:

          -  Evidence of metastatic disease or clinically enlarged lymph nodes on computed
             tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis and CT
             chest obtained within 28 days of registration (a negative biopsy is required for lymph
             nodes > 1 cm in size to confirm lack of involvement); patients with lymph nodes > 1 cm
             in whom a biopsy is deemed not feasible are not eligible; patients with elevated
             alkaline phosphatase or suspicious bone pain should also undergo baseline bone scans
             to evaluate for bone metastasis

          -  Any component of small cell carcinoma; other variant histologies are permitted
             provided the predominant (>= 50%) subtype is urothelial carcinoma

          -  Peripheral neuropathy > grade 2

          -  History of allergy or hypersensitivity to methotrexate, vinblastine, doxorubicin
             (doxorubicin hydrochloride), cisplatin, gemcitabine (gemcitabine hydrochloride),
             carboplatin or filgrastim or pegfilgrastim

          -  Another active second malignancy other than non-melanoma skin cancers and biochemical
             relapsed prostate cancer; patients that have completed all necessary therapy and are
             considered to be at less than 30% risk of relapse are not considered to have an active
             second malignancy and are eligible for enrollment

          -  Prior systemic doxorubicin for patients who have creatinine clearance that meets >= 50
             ml/min

          -  Uncontrolled illness including, but not limited to, ongoing or active infection,
             symptomatic congestive heart failure, myocardial infarction in last 3 months, unstable
             angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that
             would limit compliance with study requirements

          -  Known to have human immunodeficiency virus (HIV) or are on combination antiretroviral
             therapy

          -  Prior radiation therapy to >= 25% of the bone marrow for other diseases or prior
             systemic anthracycline therapy; prior intravesical anthracycline therapy for
             non-muscle invasive urothelial carcinoma of the bladder is permitted

          -  Pregnant or breast-feeding; all females of childbearing potential must have a blood
             test or urine study within 2 weeks prior to registration to rule out pregnancy; a
             female of childbearing potential is any woman, regardless of sexual orientation or
             whether they have undergone tubal ligation, who meets the following criteria: 1) has
             not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
             postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in
             the preceding 24 consecutive months)