Lovastatin and Pembrolizumab for the Treatment of Patients with Recurrent or Metastatic Head and Neck Cancer, LAPP Trial
Head and Neck Cancer
Unknown Primary
18 Years and older, Male and Female
WINSHIP6229-24 (primary)
NCI-2024-06118
STUDY00007740
Summary
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.
Objectives
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 OBJECTIVES:
I. To evaluate the anti-tumor activity of the combination of by assessing progression-free survival (PFS) and overall survival (OS).
II. To further define the toxicities associated with these regimens in patients with recurrent/metastatic (RM) head and neck squamous cell carcinoma (HNSCC).
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.
Eligibility
- Adult patients, male or female, aged = 18, able to provide informed consent
- Subjects with pathologically proven, recurrent or metastatic 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.)4.0 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 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
Treatment Sites in Georgia
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