Inclusion Criteria:

- Age 18 years

- ECOG Performance status of 2 (see section 11.1, Appendix A)

- Histologically confirmed UC of the bladder, urethra, ureter or renal pelvis with
Rb+/CDKN2A- based on immunohistochemistry (IHC) of tissue blocks or unstained slides
performed within a CLIA-certified laboratory at UNC; if stage I of original cohort
indicates futility, molecular requirement for eligibility will change to Rb+/CCND1
overexpression (also based on IHC); see statistical section, section 8.0)

- Metastatic disease that is not amenable to curative surgery or radiation

- Prior treatment with two prior cytotoxic regimens; prior therapy must have
consisted of at least one of the following: cisplatin, carboplatin, paclitaxel,
docetaxel or gemcitabine. If the only prior cytotoxic therapy was administered in the
perioperative i.e. neoadjuvant or adjuvant settings, patient is eligible provided the
interval from end of therapy to the diagnosis of metastatic disease is less than one
year.

- Progressive disease during or after treatment with at least one of the agents listed
above

- At least one measurable disease site (as defined by RECIST1.1) that has not been
previously irradiated

- No prior therapy with a CDK 4/6 inhibitor

- Washout period should be at least 2 weeks for prior chemotherapy or radiation therapy
3.1.10 Resolution of all acute toxic effects of prior chemotherapy, radiotherapy,
surgery to grade 1 per NCI CTCAEv4 except neuropathy which may be grade 2

- No active brain metastases

- Adequate bone marrow, liver and renal functions as assessed by the following:

- Hemoglobin 8 g/dL;

- Absolute neutrophil count 1,500/uL;

- Platelets 75,000 g/uL;

- Total bilirubin 1.5 times upper limit of normal (ULN);

- ALT and AST 2.5 times ULN;

- serum creatinine 2.5 times ULN;

- Negative serum pregnancy test in women of child-bearing potential within 7 days of D1
of treatment

- If fertile, agree to use effective contraception (condom or other barrier methods,
oral contraceptives, implantable contraceptives, intrauterine devices) during trial

- Life expectancy greater than 3 months

- Subject must be able to give written IRB approved informed consent and be able to
follow protocol requirements

Exclusion Criteria:

- Any prior treatment with any investigational drug within the preceding 4 weeks

- Any concurrent active malignancy requiring treatment (other than basal or squamous
cell carcinoma of the skin, carcinoma in situ of the cervix, superficial bladder
tumors, other malignancies curatively treated > 3 years prior to study entry) or
patients with adenocarcinoma of the prostate that has been surgically treated and
with a post-treatment PSA that is non-detectable.

- Unstable systemic disease or active uncontrolled infection

- Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to
study entry

- Not willing to avoid grapefruit, grapefruit juices, grapefruit hybrids, Seville
oranges, pummelos, and exotic citrus fruits from 7 days prior to the dose of study
medication and during the entire study due to potential CYP3A4 interaction with the
study medication. Orange juice is allowed.

- Intake of any herbal preparations or medications (including, but not limited to,
Saint John's Wort and ginkgo biloba) and dietary supplements within 7 days prior to
first dose of study drug

- Unable or unwilling to discontinue use of any drug known to be a strong or moderate
inhibitor or inducer of CYP3A4 (prohibited inducers and inhibitors must be
discontinued within 2 weeks prior to first dose of study drug; see section 11.2
Appendix B); unable or unwilling to discontinue use of any proton pump inhibitor; see
section 11.2, Appendix B

- Any malabsorption problem that, in the investigator's opinion, would prevent adequate
absorption of the study drug

- Inability to swallow oral medications

- Pregnant or breast-feeding

- Substance abuse, or medical, psychological or social conditions that may interfere
with the patient's participation in the study or the evaluation of the study results

- Other serious, ongoing, non-malignant disease or infection that would compromise
protocol objectives

Minimum Eligible Age: 18 Years

Maximum Eligible Age: N/A

Eligible Gender: Both