Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy in Patients With High-Grade Upper Tract Urothelial Carcinoma

Inclusion Criteria:

- Histologically confirmed high-grade upper tract transitional cell carcinoma at MSKCC
or a participating site and/or radiographically visible tumor stage T2-T4a N0/X M0
disease with positive selective urinary cytology or high-grade concomitant bladder
tumor. Hydronephrosis associated with tumor on biopsy will be considered invasive by
definition.

- Medically appropriate candidate for radical nephroureterectomy or ureterectomy as per
MSKCC or a participating site attending urologic oncologist

- Karnofsky Performance Status ≥ 70%

- Age ≥ 18 years of age

- Required Initial Laboratory Values:

- Absolute neutrophil count ≥ 1500 cells/mm3

- Platelets ≥ 100,000 cells/mm3

- Hemoglobin ≥ 9.0g/dL

- Bilirubin ≤ 1.2

- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for the
institution

- Alkaline phosphatase ≤ 2.5 x ULN for the institution

- Serum creatinine ≤ 1.3 mg/dL if male or ≤ 1.1 mg/dL if female OR calculated
creatinine clearance ≥ 55 ml/min/1.73m^2 If female of childbearing potential,
serum pregnancy test is negative.

- Patients with reproductive potential must use an effective method to avoid pregnancy
for the duration of the trial.

ml/min/1.73m2 using the formula: CKD epi : GFR = 141 X min(Scr/κ,1)α X max(Scr/κ,1)-1.209 X
0.993Age X 1.018 [if female] X 1.159 [if black]

- Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for
females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max
indicates the maximum of Scr/k or 1.

- If female of childbearing potential, serum pregnancy test is negative.

- Patients with reproductive potential must use an effective method to avoid pregnancy
for the duration of the trial

Exclusion Criteria:

- Concomitant bladder urothelial carcinoma is acceptable if it is organ confined and
surgically resectable.

- Presence of carcinoma in situ (CIS)

- Prior systemic chemotherapy (prior intravesical therapy is allowed)

- Prior radiation therapy to the bladder

- Evidence of NYHA functional class III or IV heart disease.

- Serious intercurrent medical or psychiatric illness, including serious active
infection.

- Preexisting sensory grade 3 neuropathy

- Major surgery or radiation therapy < 4 weeks of starting study treatment.

- Concomitant use of any other investigational drugs

- Any of the following within the 6 months prior to study drug administration:

myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft,
symptomatic congestive heart failure, cerebrovascular accident or transient ischemic
attack, or pulmonary embolism.

- Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.0 grade ≥ 2.

- Uncontrolled hypertension (>150/100 mmHg despite optimal medical therapy).

- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness or other active infection. Patients with HIV but no evidence of
AIDS will be considered candidates.

- Concurrent treatment on another clinical trial involving an intervention which may
affect the primary endpoint. Supportive care trials or non-treatment trials, e.g. QOL,
are allowed.

- Ongoing treatment with therapeutic doses of warfarin or low molecular weight heparin
(low dose warfarin up to 2 mg po daily or use of subcutaneous low molecular weight
heparin for thromboembolic prophylaxis is allowed).

- Pregnancy or breast-feeding. Patients must be surgically sterile or be postmenopausal,
or must agree to use effective contraception during the period of therapy. The
definition of effective contraception will be based on the judgment of the MSKCC and
participating site PI. Male patients must be surgically sterile or agree to use
effective contraception