Patient case: 64-year-old male with head and neck squamous cell carcinoma; genetic feature: CDKN2A

Clinical trial: Pharmacodynamic Study to Assess the Anti-proliferative Activity of the PARP Inhibitor Olaparib in Patients With HPV Positive and HPV Negative HNSCC

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: 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 <= 1.5 x institutional ULN OR creatinine clearance >= 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)

Relevance to patient case: not relevant