Study of Gemcitabine, Carboplatin, and Panitumumab (GCaP) as Neoadjuvant Chemotherapy in Patients With Muscle-Invasive Bladder Cancer

Inclusion Criteria:

- Histologically confirmed muscle invasive transitional cell carcinoma of the bladder
at MSKCC (Note: urothelial carcinoma invading into the prostatic stroma with no
histologic muscle invasion is allowed, provided the extent of disease is confirmed
via imaging and/or EUA.)

- Clinical stage T2-T4a N0/X M0 disease.

- Medically appropriate candidate for radical cystectomy as per MSKCC attending
urologic oncologist

- Karnofsky Performance Status ≥ 80%

- 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 ≤ 1.5 the upper limit of normal (ULN) for the institution

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

- Alkaline phosphatase ≤ 2.5 x ULN for the institution

- Serum magnesium > 1.4 mEq/L

- Serum creatinine ≤ 2.0 mg/dL

- Cisplatin ineligibility based on one or more of the following criteria:

Estimated glomerular filtration rate (eGFR) 30-59 ml/min/1.73m2 using the CKD-EPI
equation:(http://nephron.org/MDRD_GFR.cgi) :

eGFR = 141 x min(Scr/k, 1)a x max(Scr/k, 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.

- Grade 2 sensory neuropathy

- Grade 2 hearing loss

- Patients must provide a pretreatment saliva sample for genomic analysis.

Exclusion Criteria:

- Prior systemic chemotherapy (prior intravesical therapy is allowed)

- Serious intercurrent medical or psychiatric illness.

- Prior radiation therapy to the bladder.

- Concomitant use of any other investigational drugs

- Any of the following within the 6 months prior to study drug administration:
myocardial infarction, grade 2 or greater peripheral vascular disease, arterial
thrombotic event, visceral arterial ischemia, cerebrovascular ischemia, transient
ischemic attack, percutaneous transluminal angioplasty or stent, or unstable angina.

Symptomatic and/or serious uncontrolled arrhythmia

- Symptomatic congestive heart failure (NYHA class III or IVI)

- History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or
evidence of interstitial lung disease on baseline chest CT scan.

- History of any medical or psychiatric condition or laboratory abnormality that in the
opinion of the investigator may increase the risk associated with the study
participation or investigational product(s) administration or may interfere with the
interpretation of the results.

- Major surgery requiring general anesthesia within 21 days or minor surgery within 14
days of study enrollment. Subjects must have recovered from surgery related
toxicities.

- Pulmonary embolism, deep vein thrombosis, or other significant venous event ≤ 8 weeks
before enrollment

- Known allergy or hypersensitivity to any component of the study treatment(s)

- Active infection requiring systemic treatment or any uncontrolled infections ≤14 days
prior to enrollment.

- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness.

- Concurrent treatment on another clinical trial. Supportive care trials, surgical
clinical trials or non-treatment trials, e.g. QOL, are allowed.

- Ongoing treatment with therapeutic doses of warfarin (low dose warfarin up to 2 mg po
daily 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 and for two (2) months following the last dose of panitumumab. The definition
of effective contraception will be based on the judgment of the principal
investigator or a designated associate. Male patients must be surgically sterile or
agree to use effective contraception.