pharmacodynamic study to assess the anti-proliferative activity of the parp inhibitor olaparib in patients with hpv positive and hpv negative hnscc

Conditions: Squamous Cell Carcinoma of the Head and Neck

Summary: this is an open label pilot study evaluating the pharmacodynamics and safety of single agent olaparib administered at 300mg bid (twice a day) for 14 days orally in patients with human papillomavirus (hpv) -positive and human papillomavirus (hpv)-negative head and neck squamous cell carcinoma (hnscc)


Eligibility criteria:
inclusion criteria: * histologically confirmed hnscc with surgically resectable disease * no prior chemotherapy or radiation therapy as treatment for the observed hnscc * patients must provide written informed consent * age \>=18 years of age * eastern cooperative oncology group (ecog) performance status score of \<2 * normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below: * hemoglobin \>= 10 g/dl and no blood transfusions in the 28 days prior to entry/randomization * absolute neutrophil count \>=1.5 x 10\^9/l * no features suggesting of mds/aml on peripheral blood smear * white blood cells \> 3 x 10\^9/l * platelet count \>= 100 x 10\^9/l * total bilirubin \<= 1.5 x institutional upper limit of normal (uln) * ast (sgot)/alt (sgpt) \< 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be \< 5x uln * serum creatinine \ = 50 ml/min/1.73 m\^2 for patients with creatinine levels above institutional normal * women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of the study participation and must have negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial * must be abler to understand and sign a written informed consent document exclusion criteria: * patients with known brain metastases. patients may have received wbrt within 14 days or focal radiation within 1 week of cycle 1, day 1. the patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment * women must not be pregnant or breastfeeding * patients with known hypersensitivity to olaparib or any of the excipients of the product * patients receiving any other investigational agents within 4 weeks of starting the study * involvement in the planning and/or conduct of the study * any previous treatment with a parp inhibitor, including olaparib * concomitant use of known cyp3a4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin, and nelfinavir * persistent toxicities (\>=ctcae grade 2) * resting ecg with qtc \>470msec on 2 or more time points within a 24 hour period or family history of long qt syndrome * blood transfusions within 1 month prior to study start * patients with myelodysplastic syndrome/acute myeloid leukemia * major surgery within 14 days of starting study treatment and patients must have recovered from any effects of any major surgery * patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. * unable to swallow oral medication * immunocompromised patients, e.g., patients who are known to be serologically positive for hiv and are receiving antiviral therapy * known active hepatic disease * uncontrolled seizures * previous cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for 5 years * currently on warfarin(subcutaneous heparin is permitted)