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

Yale University

Status and phase

Withdrawn

Phase 1

Conditions

Squamous Cell Carcinoma of the Head and Neck

Treatments

Drug: Olaparib

Study type

Interventional

Funder types

Other

Identifiers

NCT02686008

1409014536

Details and patient eligibility

About

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)

Sex

All

Ages

18+ years old

Volunteers

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)