Inclusion

• All subjects treated under this protocol will have histologically documented cancer of one of the following types:
• Metastatic breast cancer with: I. Histologically confirmed invasive carcinoma of the breast; tumors with any ER,PR and Her2/neu status are eligible; II. Evidence of metastatic (stage IV) breast cancer, with at least one measurable lesion by RECIST criteria
• Metastatic colorectal cancer: I. Histologically confirmed adenocarcinoma of the colon or rectum; II. Evidence of local or distant progression, with at least one measurable lesion by RECIST criteria
• Metastatic melanoma with CDK4 mutation or amplification
• Cisplatin-refractory, unresectable germ cell tumors
• The following tumor types if tissues tests positive for CCND1 amplification; Esophageal cancer, especially squamous cell - cohorts to be analyzed separately, Head and neck squamous cell cancer, Breast especially those with luminal B expression profile, ER positively, and high Ki67 expression. (in addition to breast cancer patients above)., Liposarcoma, Any histology if already known to carry the amplification.
• The subject has disease that is assessable by tumor marker, physical, or radiologic means
• ECOG performance status of 0 or 1
• Bilirubin =< 1.5 x the upper limit of normal (ULN)
• Serum creatinine =< 1.5 x UNL or calculated creatinine clearance >= 60 mL/min
• For subjects without liver metastases: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN
• For subjects with liver metastases: alanine aminotransferase (ALT) and aspartate aminotransferase =< 5 x ULN
• For subjects without extensive bone metastases: alkaline phosphatase levels =< 2.5 x ULN
• For subjects with extensive bone metastases: alkaline phosphatase levels =< 5 x ULN
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelets >= 100,000/mm^3
• Hemoglobin > 9 g/dL
• All tumors must test positive for Rb expression
• The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document
• Sexually active subjects (male and female) must use accepted methods of contraception during the course of the study and for 3 months after the last dose of protocol drug(s)
• Female subjects of childbearing potential must have a negative pregnancy test at screening; females of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months
• 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, or ovarian suppression

Exclusion

• The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) within 3 weeks (or nitrosoureas or mitomycin C within 6 weeks) before the first dose of PD 0332991
• The subject has received any other type of investigational agent on a protocol within 28 days before the first dose of study treatment
• The subject has not recovered from clinically-meaningful toxicity due to prior therapy (i.e., back to baseline or Grade =< 1), with the exception of neurotoxicity and alopecia
• The subject has untreated or uncontrolled brain metastases or evidence of leptomeningeal involvement of disease
• The subject has uncontrolled intercurrent illness including, but not limited to: I. Ongoing or active infection; II. Diabetes mellitus; III. Hypertension; IV. Symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months
• The subject has a baseline corrected QT interval (QTc) > 470 ms
• The subject is pregnant or breastfeeding
• The subject is known to be positive for the human immunodeficiency virus (HIV)
• Note: baseline HIV screening is not required
• The subject is unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee
• If a subject requires additional anticancer treatment, he or she must be withdrawn from the study (with the exception of palliative radiotherapy, which may be allowed during the study with the approval of the sponsor)
• No concurrent investigational agents will be permitted
• No concurrent anticancer treatment will be permitted
• High dose (> 60mg/day) or chronic (> 3months) steroid use is not allowed during the course of this study as it may interfere with metabolism of the study drug