Trial Title:
Lovastatin and Pembrolizumab for the Treatment of Patients with Recurrent or Metastatic Head and Neck Cancer, LAPP Trial
NCT ID:
NCT06636734
Condition:
Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC V8
Human Papillomavirus-Related Neck Squamous Cell Carcinoma of Unknown Primary
Metastatic Head and Neck Squamous Cell Carcinoma
Metastatic Hypopharyngeal Squamous Cell Carcinoma
Metastatic Laryngeal Squamous Cell Carcinoma
Metastatic Nasopharyngeal Squamous Cell Carcinoma
Metastatic Oral Cavity Squamous Cell Carcinoma
Metastatic Oropharyngeal Squamous Cell Carcinoma
Metastatic Paranasal Sinus Squamous Cell Carcinoma
Recurrent Head and Neck Squamous Cell Carcinoma
Recurrent Hypopharyngeal Squamous Cell Carcinoma
Recurrent Laryngeal Squamous Cell Carcinoma
Recurrent Nasopharyngeal Squamous Cell Carcinoma
Recurrent Oral Cavity Squamous Cell Carcinoma
Recurrent Oropharyngeal Squamous Cell Carcinoma
Recurrent Paranasal Sinus Squamous Cell Carcinoma
Stage IV Hypopharyngeal Carcinoma AJCC V8
Stage IV Laryngeal Cancer AJCC V8
Stage IV Lip and Oral Cavity Cancer AJCC V8
Stage IV Nasopharyngeal Carcinoma AJCC V8
Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC V8
Stage IV Sinonasal Cancer AJCC V8
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Nasopharyngeal Carcinoma
Squamous Cell Carcinoma of Head and Neck
Laryngeal Neoplasms
Mouth Neoplasms
Recurrence
Pembrolizumab
Lovastatin
L 647318
Dihydromevinolin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (lovastatin, pembrolizumab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT or PET/CT
Arm group label:
Treatment (lovastatin, pembrolizumab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Lovastatin
Description:
Given PO
Arm group label:
Treatment (lovastatin, pembrolizumab)
Other name:
Lovastatin Sodium
Other name:
Mevacor
Other name:
Mevinolin
Other name:
Monacolin K
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (lovastatin, pembrolizumab)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Treatment (lovastatin, pembrolizumab)
Other name:
BCD-201
Other name:
GME 751
Other name:
GME751
Other name:
Keytruda
Other name:
Lambrolizumab
Other name:
MK 3475
Other name:
MK-3475
Other name:
MK3475
Other name:
Pembrolizumab Biosimilar BCD-201
Other name:
Pembrolizumab Biosimilar GME751
Other name:
Pembrolizumab Biosimilar QL2107
Other name:
QL2107
Other name:
SCH 900475
Other name:
SCH-900475
Other name:
SCH900475
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT
Arm group label:
Treatment (lovastatin, pembrolizumab)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
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.
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.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Emory University Hospital/Winship Cancer Institute
Address:
City:
Atlanta
Zip:
30322
Country:
United States
Contact:
Last name:
Ardith C. Deshay
Phone:
404-686-1858
Email:
ardith.deshay.deshay@emory.edu
Contact backup:
Last name:
Nicole C. Schmitt, MD, FACS
Start date:
October 21, 2024
Completion date:
October 31, 2028
Lead sponsor:
Agency:
Emory University
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Emory University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06636734
