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

NCT02686008 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: 1409014536
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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)

Conditions

Squamous Cell Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (1)

• Change in Level of IHC-Ki-67 expression

  Tissue biopsy sections will be analyzed for proliferation (IHC-Ki-67) Ki-67 is a nuclear non-histone protein that is present at low levels in quiescent cells but is increased in proliferating cells. Thus, Ki-67 reactivity, defined as percent tumor cells staining positive as measured by immunohistochemical (IHC) staining, is a specific nuclear marker for cell proliferation.

  Baseline and 14 days

Secondary Outcomes (2)

• Change in Tissue apoptosis

  Baseline and 14 days

• Change in DNA repair pathways

  Baseline and 14 days

Study Arms (2)

HPV negative tumors

EXPERIMENTAL

10 patients with HPV negative tumors: Non-oropharyngeal tumors or p16 negative and HPV negative oropharyngeal tumors

Drug: Olaparib

HPV positive tumors

EXPERIMENTAL

10 patients with HPV positive tumors: p16 positive and HPV positive tumors

Drug: Olaparib

Interventions

Olaparib DRUG

Patients will receive olaparib administered at 300 mg bid x 14 days orally

Also known as: Lynparza

HPV negative tumors; HPV positive tumors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

olaparib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Anne Chiang, MD, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2015
• First Posted: February 19, 2016
• Study Start: January 1, 2018
• Primary Completion: January 1, 2019
• Study Completion: July 1, 2019
• Last Updated: January 13, 2020

Record last verified: 2020-01