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

• Status: Withdrawn
• Trial end date: 2019-07-01
• Target enrollment: 0
• Participant gender: All

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)

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Yale University
• Treatments: Olaparib

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 <= 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)