A Phase II Study Of PD0332991 in Patients With Advanced or Metastatic Liposarcoma

Inclusion Criteria:

- A diagnosis of liposarcoma confirmed at MSKCC. Because myxoid / round cell
liposarcoma does not have significant CDK4 amplification, patients with this subtype
are not eligible.

- Metastatic and/or locally advanced or locally recurrent disease that is not
surgically resectable, with evidence of disease progression, either clinically or
radiographically, as determined by the investigator

- All patients must have measurable disease as defined by RECIST 1.1. Measurable
disease is defined as at least one lesion that can be accurately measured in at least
one dimension (longest diameter to be recorded). Each lesion must be >10 mm when
measured by CT, MRI or caliper measurement by clinical exam; or >20 mm when measured
by chest x-ray. Lymph nodes must be > 15 mm in short axis when measured by CT or MRI.

- A minimum of 1 prior systemic regimen for recurrent/metastatic disease. Note: This
requirement does not apply to patients enrolled in the Expansion Cohort. The last
dose of systemic therapy (include targeted therapies) must have been given at least 2
weeks prior to initiation of therapy. Patients receiving BCNU or mitomycin C must
have received their last dose of such therapy at least 6 weeks prior to initiation of
therapy.

- Patients with brain metastasis that have been treated with definitive surgery or
radiation and have been clinically stable for 3 months are eligible.

- Age > or = 18 years.

- ECOG performance status 0 or 1.

- Adequate organ and marrow function as defined below (ULN indicates institutional
upper limit of normal):

Absolute neutrophil count ≥ 1.5x109/L Hemoglobin ≥ 9.0 g/dL WBC ≥ 3.0x109/L Platelets ≥
100x109/L Total bilirubin ≤ 1.5 x ULN except for patients with known Gilbert syndrome
AST(SGOT)/ALT(SGPT) ≤ 3 x institutional ULN Serum creatinine ≤ 1.5 x ULN or Creatinine
Clearance > 50 mL/min (calculated by Cockcroft-Gault method)QTc interval ≤ 470 msec

- Patients must not have current evidence of another malignancy that requires
treatment.

- The effects of PD0332991 on the developing human fetus at the recommended therapeutic
dose are unknown. Women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence). Women must
not breast feed while on study.

- Ability to understand and the willingness to sign a written informed consent
document.

- Ability to swallow intact PD0332991 capsules.

- Patients‟ tumors must express Rb, as assessed using an historical biopsy sample if
available or a newly obtained tumor sample. Samples must demonstrate ≥1+ staining for
Rb. Patients' tumors must also have evidence of CDK4 amplification by FISH. Note:
This does not apply to patients enrolled in the Expansion Cohort.

Exclusion Criteria:

- Patients who have not recovered from adverse events of prior therapy to ≤ NCI
CTCAEv4.0 Grade 1.

- Patients receiving any other investigational agents.

- Patients who have received prior treatment with a selective CDK4 inhibitor

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to PD0332991.

- Uncontrolled intercurrent illness including, but not limited to, known ongoing or
active infection, including HIV, active hepatitis B or C, symptomatic congestive
heart failure, unstable angina pectoris, cardiac arrhythmia (specifically, atrial
fibrillation or ventricular dysrhythmias except ventricular premature contractions),
or psychiatric illness/social situations that would limit compliance with study
requirements.

- Pregnant women and women who are breast-feeding.

- Patients with a history of long-QT syndrome or documented family history of long-QT
syndrome. Patients who must remain on drugs that prolong the QT interval.

- PD0332991 is a substrate of CYP3A. Caution should be exercised when dosing PD0332991
concurrently with CYP3A inducers or inhibitors. Furthermore, patients who are taking
concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4
should be switched to alternative medications to minimize any potential risk. A list
of CYP3A4 substrates, inducers and/or inhibitors is provided in Appendix B. The
following medications with strong potential for interaction are not allowed:
indinavir nelfinavir ritonavir clarithromycin itraconazole ketoconazole nefazodone
saquinavir telithromycin carbamazepine phenobarbital phenytoin pioglitazone rifabutin
rifampin St. John's wort Troglitazone