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

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Yale University

Status and phase

Phase 1


Squamous Cell Carcinoma of the Head and Neck


Drug: Olaparib

Study type


Funder types




Details and patient eligibility


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)




18+ years old


No Healthy Volunteers

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)

Trial design

Primary purpose




Interventional model

Parallel Assignment


None (Open label)

0 participants in 2 patient groups

HPV negative tumors
Experimental group
10 patients with HPV negative tumors: Non-oropharyngeal tumors or p16 negative and HPV negative oropharyngeal tumors
Drug: Olaparib
HPV positive tumors
Experimental group
10 patients with HPV positive tumors: p16 positive and HPV positive tumors
Drug: Olaparib

Trial contacts and locations



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