Inclusion Criteria

- INCLUSION CRITERIA:

Cohort 1 only (urothelial progressive disease)

- Patients must have a diagnosis of urothelial carcinoma of the bladder, urethra,
ureter, or renal pelvis, with histological confirmation at the NIH.

- Patients must have progressive metastatic disease. Progressive disease will be
defined as new or progressive lesions on cross-sectional imaging.

- Patients must have at least one measurable site of disease

Cohort 2 only (Bone-only)

- Patients must have a diagnosis of urothelial carcinoma of the bladder, urethra,
ureter, or renal pelvis, with histological confirmation at the NIH.

- Patients must not have measurable progressive disease

- Patient must have appearance of at least one new bone lesion.

Cohort 3 (Rare histologies)

- Patient must have a diagnosis of non-transitional cell carcinoma of the bladder,
urethra, ureter, or renal pelvis including but not limited to squamous cell,
neuroendocrine, adenocarcinoma including urachal and sarcomatoid.

- Patients must have progressive metastatic disease. Progressive disease will be
defined as new or progressive lesions on cross-sectional imaging.

- Patients must have at least one measurable site of disease

All cohorts

- Patients must have been previously treated, as defined by treatment with at least one
prior cytotoxic regimen or agent.

- Age greater than or equal to 18 years. Because no dosing or adverse event data are
currently available on the use of cabozantinib in patients < 18 years of age,
children are excluded from this study, but may be eligible for future pediatric
trials.

- ECOG performance status less than or equal to 2 (Karnofsky > 60%

- Adequate organ function as defined by the following criteria:

- Hemoglobin greater than or equal to 9 g/dL

- Absolute neutrophil count (ANC) greater than or equal to 1500/microL

- Platelets greater than or equal to 100,000/?L

- Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT])
and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) less
than or equal to 3.0 times upper limit of normal (ULN); less than or equal to 5.0
times ULN in cases of liver metastases

- Total serum bilirubin less than or equal to 1.5 times the upper limit of normal
(ULN). For subjects with known Gilbert's disease or similar syndrome with slow
conjugation of bilirubin, total bilirubin less than or equal to 3.0 mg/dL

- Serum creatinine less than or equal to 1.5 X institutional upper limits of normal or
for patients with creatinine levels above 1.5 x institutional normal: creatinine
clearance greater than or equal to 50 mL/min/1.73 m2 by 24 hour urine collection or
estimated creatinine clearance of greater than or equal to 50 mL/min. For creatinine
clearance estimation , the Cockcroft and Gault equation should be used:

- Male: CrCl (mL/min) = (140 - age) times wt (kg) / (serum creatinine times 72)

- Female: Multiply above result by 0.85

- Urine protein/creatinine ratio (UPCR) less than or equal to 2

- Patient must be able to provide either archival tumor samples (H& E slides and one
paraffin block or 10 unstained slides) or undergo tumor biopsy.

- Patient must be capable of understanding and complying with protocol requirements and
is willing to give informed consent

- The effects of XL184 on the developing human fetus are unknown. For this reason and
because tyrosine kinase inhibitors agents are known to be teratogenic, women of
childbearing potential and men must agree to use adequate contraception prior to
study entry and for the duration of study participation. Should a woman become

pregnant or suspect she is pregnant while she or her partner is participating in this
study, she should inform her treating physician immediately. Men treated or enrolled on
this protocol must also agree to use adequate contraception prior to the study, for the

duration of study participation, and 4 months after completion of XL184 administration.

Sexually active subjects (men and women) must agree to use medically accepted barrier
methods of contraception (e.g., male or female condom) during the course of the study and
for 4 months after the last dose of study drug(s), even if oral contraceptives are also
used. All subjects of reproductive potential must agree to use both a barrier method and a
second method of birth control during the course of the study and for 4 months after the
last dose of study drug(s).

- Women of childbearing potential must have a negative pregnancy test at screening. Women
of childbearing potential include women who have experienced menarche and who have not
undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or
bilateral oophorectomy) or are not postmenopausal. Postmenopause is defined as amenorrhea
greater than or equal to 12 consecutive months. Note: women who have been amenorrheic for
12 or more months are still considered to be of childbearing potential if the amenorrhea
is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other
reversible reason.

EXCLUSION CRITERIA:

- The subject has received cytotoxic chemotherapy (including investigational cytotoxic
chemotherapy) or biologic agents (eg, cytokines or antibodies) within 3 weeks, or
nitrosoureas or mitomycin within 6 weeks before the first dose of study treatment.

- Prior treatment with cabozantinib or other small molecule inhibitors of VEGFR.

- The subject has received radiation therapy:

- to the thoracic cavity or gastrointestinal tract within 3 months before the first
dose of study treatment

- to bone or brain metastasis within 14 days before the first dose of study treatment

- to any other site(s) within 28 days before the first dose of study treatment

- The subject has received radionuclide treatment within 6 weeks before the first dose
of study treatment

- The subject has received prior treatment with a small molecule kinase inhibitor or a
hormonal therapy (including investigational kinase inhibitors or hormones) within 14
days or five half-lives of the compound or active metabolites, whichever is longer,
before the first dose of study treatment.

- The subject has received any other type of investigational agent within 28 days
before the first dose of study treatment.

- The subject has not recovered to baseline or CTCAE . Grade 1 from toxicity due to all
prior therapies except alopecia and other non-clinically significant AEs.

- The subject has a primary brain tumor

- The subject has active brain metastases, leptomeningeal or epidural disease (Note:
Subjects with brain metastases previously treated with whole brain radiation or
radiosurgery or subjects with epidural disease previously treated with radiation or
surgery who are asymptomatic and do not require steroid treatment for at least 2
weeks before starting study treatment are eligible. Neurosurgical resection of brain
metastases or brain biopsy is permitted if completed at least 3 months before
starting study treatment. Baseline brain scans are not required to confirm
eligibility.)

- The subject has prothrombin time (PT)/ International Normalized Ratio (INR) or
partial thromboplastin time (PTT) test greater than or equal to 1.3 times the
laboratory ULN within 7 days before the first

dose of study treatment.

- The subject requires treatment, in therapeutic doses, with anticoagulants such as
warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or
antiplatelet agents (e.g., clopidogrel) prior to initiation of protocol therapy. Low
dose aspirin (less than or equal to 81 mg/day), low-dose warfarin (less than or
equal to 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are
permitted. Subjects will be permitted to use anticoagulation as described if
treatment is required while they are enrolled on the protocol.

- The subject requires chronic concomitant treatment of strong CYP3A4 inducers (e.g.,
dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin,
phenobarbital, and St. John's Wort).

Because the lists of these agents are constantly changing, it is important to regularly
consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/;
medical reference texts such as the Physicians Desk Reference may also provide this

information. As part of the enrollment/informed consent procedures, the patient will be
counseled on the risk of interactions with other agents, and what to do if new medications
need to be prescribed or if the patient is considering a new over-thecounter medicine or
herbal product.

- The subject has experienced any of the following within 3 months before the first
dose of study treatment:

- clinically-significant hematemesis or gastrointestinal bleeding

- hemoptysis of greater than or equal to 0.5 teaspoon (greater than or equal to 2.5 mL)
of red blood

- any other signs indicative of pulmonary hemorrhage

- The subject has tumor invading (or concern for invasion) major blood vessels

- Other severe acute or chronic medical or psychiatric condition, or laboratory
abnormality that may increase the risk associated with study participation or study
drug administration, or may interfere with the interpretation of study results, and
in the judgment of the Investigator would make the patient inappropriate for entry
into this

study.

- The subject has evidence of tumor invading the GI trac (esophagus, stomach, small or
large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor
within 28 days before the first dose of cabozantinib.

- The subject has uncontrolled, significant intercurrent or recent illness including,
but not limited to, the following conditions:

1. Cardiovascular disorders including

i. Congestive heart failure (CHF): New York Heart Association (NYHA) Class III
(moderate) or Class IV (severe) at the time of screening

ii. Concurrent uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic, or
> 90 mm Hg diastolic despite optimal antihypertensive treatment (BP must be controlled at
screening)

iii. Any history of congenital long QT syndrome

iv. Any of the following within 6 months before the first dose of study treatment:

- unstable angina pectoris

- clinically-significant cardiac arrhythmias

- stroke (including TIA, or other ischemic event)

- myocardial infarction

- thromboembolic event requiring therapeutic anticoagulation (Note:

subjects with a venous filter (e.g. vena cava filter) are not eligible for this study)

b. Gastrointestinal disorders particularly those associated with a high risk of
perforation or fistula formation including:

i. Any of the following within 28 days before the first dose of cabozantinib

- active peptic ulcer disease,

- active inflammatory bowel disease (including ulcerative colitis and

Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis

- active malabsorption syndrome

ii. Any of the following within 6 months before the first dose of study treatment:

(1) abdominal fistula

(2) gastrointestinal perforation

(3) bowel obstruction or gastric outlet obstruction

(4) intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must
be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred
more than 6 months ago.

c. Other disorders associated with a high risk of fistula formation including PEG tube
placement within 3 months before the first dose of study therapy.

d. Other clinically significant disorders such as:

i. active infection requiring systemic treatment within 28 days before the first dose of
study treatment

ii. serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of
study treatment

iii. history of organ transplant

iv. concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before
the first dose of study treatment

v. history of major surgery as follows:

1. Major surgery within 3 months of the first dose of cabozantinib if there were no
wound healing complications or within 6 months of the first dose of cabozantinib if
there were wound complications.

2. Minor surgery within 1 months of the first dose of cabozantinib if there were no
wound healing complications or within 3 months of the first dose of cabozantinib if
there were wound complications

In addition, complete wound healing from prior surgery must be confirmed at least 28 days
before the first dose of cabozantinib irrespective of the time from surgery

- The subject is unable to swallow tablets

- The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) >
500 ms within 28 days before treatment initiation.

- The subject has a previously identified allergy or hypersensitivity to components of
the study treatment formulation.

- The subject is unable or unwilling to abide by the study protocol or cooperate fully
with the investigator or designee.

- The subject has had within 2 years before the start of study treatment evidence of
another malignancy which required systemic treatment

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with the study agents. In addition,
these patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.