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Purpose

This phase II trial tests how well lovastatin and pembrolizumab work in treating patients with head and neck cancer that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Lovastatin is a drug used to lower the amount of cholesterol in the blood and may also cause tumor cell death. In addition, studies have shown that lovastatin may make the tumor cells more sensitive to immunotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving lovastatin and pembrolizumab may kill more tumor cells in patients with recurrent or metastatic head and neck cancer.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Adult patients, male or female, aged ≥ 18, able to provide informed consent - Subjects with pathologically proven, recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) involving the oral cavity, oropharynx, larynx, hypopharynx, nasopharynx, or paranasal sinuses; patients with unknown primary HNSCC involving the cervical lymph nodes can be included if human papillomavirus (HPV)-positive - PD-L1 combined positive score (CPS) ≥ 1 (i.e., must be a candidate for treatment with pembrolizumab alone) - Patients must not be under consideration for salvage surgery - Measurable disease by RECIST 1.1 criteria - Life expectancy of more than 3 months, as determined by the investigator - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Recovery to baseline or ≤ grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v.)5.0 from toxicities related to any prior treatments, unless adverse events are clinically non-significant and/or stable on supportive therapy - For men or women of reproductive potential: use of highly effective contraception for at least 1 month prior to enrollment and agreement to use such a method during study participation and for an additional 8 weeks after the end of lovastatin/pembrolizumab administration - Absolute neutrophil count (ANC) ≥ 1000/mm^3 without colony stimulating factor support - Platelets ≥ 100,000/mm^3 - Hemoglobin ≥ 9 g/dL - Bilirubin ≤ 1.5 x the upper limit of normal (ULN). For subjects with known Gilbert's disease, bilirubin ≤ 3.0 mg/dL - Serum albumin ≥ 2.8 g/dl - Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 x ULN - Serum phosphorus, calcium, magnesium and potassium ≥ lower limit of normal (LLN)

Exclusion Criteria

  • Patients already taking a statin drug - Liver dysfunction precluding the use of statins - Radiation to the head and neck or other sites within 4 weeks prior to enrollment - Cytotoxic chemotherapy or any form of investigational therapy within 4 weeks prior to study treatment - Prior treatment with immune checkpoint blocking therapy - Current use of drugs that interact with lovastatin (cimetidine, spironolactone, ketoconazole, and others) - Pregnancy, lactation, or plan to become pregnant - Inability to swallow lovastatin tablets - Known allergy or prior adverse reaction to lovastatin, other statin drugs, or pembrolizumab

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Treatment (lovastatin, pembrolizumab) 		Patients receive lovastatin PO QD and pembrolizumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, and CT, MRI or PET/CT throughout the study.
  • Procedure: Biospecimen Collection
    Undergo blood sample collection
    Other names:
    • Biological Sample Collection
    • Biospecimen Collected
    • Specimen Collection
  • Procedure: Computed Tomography
    Undergo CT or PET/CT
    Other names:
    • CAT
    • CAT Scan
    • Computed Axial Tomography
    • Computerized Axial Tomography
    • Computerized axial tomography (procedure)
    • Computerized Tomography
    • Computerized Tomography (CT) scan
    • CT
    • CT Scan
    • tomography
  • Drug: Lovastatin
    Given PO
    Other names:
    • Lovastatin Sodium
    • Mevacor
    • Mevinolin
    • Monacolin K
  • Procedure: Magnetic Resonance Imaging
    Undergo MRI
    Other names:
    • Magnetic Resonance
    • Magnetic Resonance Imaging (MRI)
    • Magnetic resonance imaging (procedure)
    • Magnetic Resonance Imaging Scan
    • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
    • MR
    • MR Imaging
    • MRI
    • MRI Scan
    • MRIs
    • NMR Imaging
    • NMRI
    • Nuclear Magnetic Resonance Imaging
    • sMRI
    • Structural MRI
  • Biological: Pembrolizumab
    Given IV
    Other names:
    • BCD-201
    • GME 751
    • GME751
    • Keytruda
    • Lambrolizumab
    • MK 3475
    • MK-3475
    • MK3475
    • Pembrolizumab Biosimilar BCD-201
    • Pembrolizumab Biosimilar GME751
    • Pembrolizumab Biosimilar QL2107
    • QL2107
    • SCH 900475
    • SCH-900475
    • SCH900475
  • Procedure: Positron Emission Tomography
    Undergo PET/CT
    Other names:
    • Medical Imaging, Positron Emission Tomography
    • PET
    • PET Scan
    • Positron emission tomography (procedure)
    • Positron Emission Tomography Scan
    • Positron-Emission Tomography
    • proton magnetic resonance spectroscopic imaging
    • PT

Recruiting Locations

Emory University Hospital Midtown
Atlanta 4180439, Georgia 4197000 30308
Contact:
Ardith Deshay
404-686-1858
ardith.deshay.deshay@emory.edu

Emory University Hospital/Winship Cancer Institute
Atlanta 4180439, Georgia 4197000 30322
Contact:
Ardith C. Deshay
404-686-1858
ardith.deshay.deshay@emory.edu

More Details

Status
Recruiting
Sponsor
Emory University

Study Contact

Nicole C. Schmitt, MD, FACS
404-778-0278
nicole.cherie.schmitt@emory.edu

Detailed Description

PRIMARY OBJECTIVE: I. To evaluate anti-tumor activity of the combination of pembrolizumab and lovastatin by assessing the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). SECONDARY OBJECTIVE: I. To evaluate the anti-tumor activity of the combination of by assessing progression-free survival (PFS) and overall survival (OS). TERTIARY/EXPLORATORY OBJECTIVES: I. To assess the effects of the combination of lovastatin + pembrolizumab on immune cells in blood. II. To assess the association between efficacy measures and expression in tumors. III. To assess the association between anti-tumor activity and immune cells in the blood. OUTLINE: Patients receive lovastatin orally (PO) once daily (QD) and pembrolizumab intravenously (IV) over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, and computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET)/CT throughout the study. After completion of study treatment, patients are followed for up to 2 years.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.