PD 0332991 and Cetuximab in Patients With Incurable SCCHN

Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the head and neck. * Disease must be considered incurable. Incurable is defined as metastatic disease or a local or regional recurrence in a previously irradiated site that is unresectable (or patient declines resection). * Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with CT scan, as ≥20 mm by chest x-ray, or ≥10 mm with calipers by clinical exam. (Phase I only: patients without measurable disease by RECIST 1.1 criteria but with evaluable disease by imaging or physical exam will be eligible as well.) * Phase I only: any (or no) prior therapy for metastatic disease is allowed, including cetuximab. If a patient has not received prior standard therapy, s/he must have been offered and refused prior standard therapy. * Phase II only: * Arm 1: disease progression after at least one cycle of prior treatment with cisplatin or carboplatin for incurable disease. Prior treatment with cetuximab for incurable disease is not permitted. * Arms 2 and 3: disease progression after at least one cycle of treatment with cetuximab for incurable disease. * Phase II only: at least one line of prior therapy for incurable disease. * Phase II only: * Arms1 and 2: disease must be determined to be HPV-unrelated. HPV-unrelated SCCHN is defined as either p16-negative OPSCC or non-OPSCC (larynx, hypopharynx, oral cavity) or p16-negative unknown primary SCC presenting with a level 2 or 3 neck node. p16 will be assessed by IHC; a specimen showing any staining will be considered p16-positive. * Arm 3: disease must be HPV-related SCCHN (defined as OPSCC or unknown primary presenting with a neck mass that is either p16 positive or HPV ISH or PCR positive). * Minimum of 14 days elapsed since the end of any prior therapy. * At least 18 years of age. * Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 4.0 Grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion) * ECOG performance status ≤ 2 * Adequate bone marrow and organ function as defined below: * Absolute neutrophil count ≥ 1,500 mm3 * Platelets ≥ 100,000 mm3 * Hemoglobin \> 9 g/dL * Total bilirubin ≤ 1.5 x IULN except in the case of patients with Gilbert's disease * AST (SGOT) and ALT (SGPT) ≤ 2.5 x IULN for patients without liver metastases and ≤ 5.0 x IULN for patients with liver metastases * Alkaline phosphatase ≤ 2.5 x IULN for patients without bone metastases and ≤ 5.0 x IULN for patients with bone metastases * Serum creatinine ≤ 1.5 x IULN OR calculated creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal * Baseline corrected QT interval (QTc) \< 480 ms. * Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Available archival tumor tissue for the proposed correlative studies. * Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable). Exclusion Criteria: * Phase II, Arm 1 only: prior treatment with cetuximab. * Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE version 4.0 Grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator´s discretion) * A history of other malignancy ≤ 1 year previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only, carcinoma in situ of the cervix, or synchronous H\&N primaries. * Currently receiving any other investigational agents. * Patient must not have a history of or clinical evidence of central nervous system metastases or leptomeningeal carcinomatosis, except for individuals who have had previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medications (with the exception of Keppra) for 1 month prior to first dose of PD 0332991. * A history of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991, cetuximab, or other agents used in the study. * Treated within the last 7 days prior to Day 1 of protocol therapy with: * Food or drugs that are known to be CYP3A4 inhibitors (e.g. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, telithromycin, indinavir, ritonavir, nelfinavir, atazanavir, amprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort). * Drugs that are known to prolong the QT interval. * Drugs that are proton pump inhibitors. * Uncontrolled electrolyte disorders that can compound the effects of a QTc-prolonging drug (e.g., hypocalcemia, hypokalemia, hypomagnesemia) * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test within 28 days of study entry. Female patients must be surgically sterile or be postmenopausal, or must agree to use effective contraceptive during the period of the trial and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator or a designated associate. * Phase I and Arm 1 of Phase II: Known HIV-positivity and on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with PD 0332991. 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. Arms 2 and 3 of Phase II: patients with HIV infection and antiretroviral therapy are not excluded, as there are no pharmacokinetic tests being performed.