Clinical trial NCT02686008: Pharmacodynamic Study to Assess the Anti-proliferative Activity of the PARP Inhibitor Olaparib in Patients With HPV Positive and HPV Negative HNSCC
Official title: A Pilot Pharmacodynamic Study to Assess the Anti-proliferative Activity a of the Poly ADP Ribose Polymerase (PARP) Inhibitor Olaparib in Patients With Human Papilloma Virus (HPV) Positive and Human Papilloma Virus (HPV) Negative Head and Neck Squamous Cell Carcinoma (HNSCC)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Squamous Cell Carcinoma of the Head and Neck
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2016-02-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 \<= 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)

Primary outcomes:
measure: Change in Level of IHC-Ki-67 expression
timeFrame: Baseline and 14 days
Secondary outcomes:
measure: Change in Tissue apoptosis
timeFrame: Baseline and 14 days
measure: Change in DNA repair pathways
timeFrame: Baseline and 14 days
Other outcomes:
Locations:
Study officials:
affiliation: Yale University
name: Anne Chiang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: