Lovastatin + Pembrolizumab for Head and Neck Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Emory University
Must not be taking: Statins, Cimetidine, Spironolactone, others
Disqualifiers: Liver dysfunction, Recent radiation, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial requires that you stop taking any statin drugs and any drugs that interact with lovastatin, such as cimetidine, spironolactone, and ketoconazole, before participating.
What data supports the effectiveness of the drug pembrolizumab for head and neck cancer?
Pembrolizumab has been shown to be effective in treating recurrent or metastatic head and neck cancer, especially after other treatments like platinum-based chemotherapy have failed. It was approved by the FDA based on studies showing that some patients experienced a reduction in tumor size and that these responses could last for several months.
12345Is the combination of Lovastatin and Pembrolizumab safe for humans?
Pembrolizumab has been studied for safety in patients with head and neck cancer, showing some serious side effects like pneumonia and thyroid disorders, but it was considered to have an acceptable safety profile. However, there is no specific safety data available for the combination of Lovastatin and Pembrolizumab.
13467How does the drug combination of Lovastatin and Pembrolizumab differ from other treatments for head and neck cancer?
This drug combination is unique because it combines Lovastatin, which may enhance antitumor immunity by affecting cholesterol levels, with Pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This approach aims to improve the effectiveness of immune therapy in head and neck cancer, which typically has limited treatment options.
13689Eligibility Criteria
This trial is for patients with head and neck cancer that has either returned after getting better or spread to other body parts. Participants should have a type of cancer listed in the trial conditions, such as nasopharyngeal carcinoma or laryngeal squamous cell carcinoma.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)
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive lovastatin orally once daily and pembrolizumab intravenously on day 1 of each cycle. Cycles repeat every 21 days for up to 12 months.
12 months
1 visit every 21 days
Follow-up
Participants are monitored for safety and effectiveness after treatment completion, including blood sample collection and imaging studies.
Up to 2 years
Participant Groups
The LAPP Trial is testing lovastatin combined with pembrolizumab on recurrent or metastatic head and neck cancers. Lovastatin lowers cholesterol but may also make tumor cells more sensitive to immunotherapy, while pembrolizumab boosts the immune system's ability to fight cancer.
1Treatment groups
Experimental Treatment
Group I: Treatment (lovastatin, pembrolizumab)Experimental Treatment6 Interventions
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.
Lovastatin is already approved in United States, Canada, European Union for the following indications:
🇺🇸 Approved in United States as Mevacor for:
- High cholesterol
- Hyperlipidemia
- Cardiovascular disease prevention
🇨🇦 Approved in Canada as Lovastatin for:
- High cholesterol
- Hyperlipidemia
- Cardiovascular disease prevention
🇪🇺 Approved in European Union as Lovastatin for:
- Primary hypercholesterolaemia
- Mixed dyslipidaemia
- Prevention of cardiovascular events
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Emory University Hospital/Winship Cancer InstituteAtlanta, GA
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Who Is Running the Clinical Trial?
Emory UniversityLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]Until recently, palliative options for the treatment of platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have been cytotoxic chemotherapy and EGFR inhibitors. These agents offer limited efficacy with substantial toxicity. The development of novel immune checkpoint inhibitors has challenged the standard treatment. Pembrolizumab is a potent and highly selective humanized monoclonal antibody that blocks the interaction between PD-1, an immune checkpoint receptor and its ligands PD-L1 and -2. In August 2016, the US FDA approved the use of pembrolizumab in R/M HNSCC following disease progression on or after platinum-containing chemotherapy. This review highlights the pharmacology, therapeutic efficacy and tolerability data relevant to the use of pembrolizumab for the treatment of R/M HNSCC. Readers will gain greater insight into the HNSCC tumor microenvironment, available biomarkers, and learn about important clinical considerations associated with the use of pembrolizumab and similar immune checkpoint inhibitors.
Postoperative adjuvant radiochemotherapy with cisplatin versus adjuvant radiochemotherapy with cisplatin and pembrolizumab in locally advanced head and neck squamous cell carcinoma- the study protocol of the Adrisk trial. [2023]Most of the patients with head and neck squamous cell carcinoma (HNSCC) are diagnosed with locally advanced disease. Standards of care for curative-intent treatment of this patient group are either surgery and adjuvant radio(chemo)therapy (aRCT) or definitive chemoradiation. Despite these treatments, especially pathologically intermediate and high-risk HNSCC often recur. The ADRISK trial investigates in locally advanced HNSCC and intermediate and high risk after up-front surgery if the addition of pembrolizumab to aRCT with cisplatin improves event-free sur-vival compared to aRCT alone. ADRISK is a prospective, randomized controlled investiga-tor-initiated (IIT)-phase II multicenter trial within the German Interdisciplinary Study Group of German Cancer Society (IAG-KHT). Patients with primary resectable stage III and IV HNSCC of the oral cavity, oropharynx, hypopharynx and larynx with pathologic high (R1, extracapsular nodal extension) or intermediate risk (R0
FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. [2019]On August 5, 2016, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA injection, Merck Sharp & Dohme Corp., Kenilworth, NJ) for treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. Approval was based on the objective response rate (ORR) and duration of response (DoR) in a cohort of patients in a nonrandomized multi-cohort trial (KEYNOTE-012) that included 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. Patients received either intravenous pembrolizumab 10 mg/kg every 2 weeks or 200 mg every 3 weeks. ORR was determined by independent review according to Response Evaluation Criteria in Solid Tumors 1.1. ORR was 16% (95% confidence interval 11, 22) with a complete response rate of 5%. DoR ranged from 2.4+ months to 27.7+ months. Twenty-three of 28 responding patients (82%) had response durations of ≥6 months. Safety was evaluated in 192 patients with HNSCC receiving at least one dose of pembrolizumab. Frequent (≥2%) serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders. The benefit-risk profile of pembrolizumab was considered acceptable in this patient population. As a condition of accelerated approval, Merck is required to conduct a confirmatory trial; this trial, KEYNOTE-040, is ongoing.
Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. [2023]Pembrolizumab exhibits anticancer efficacy in platinum-sensitive or platinum-unfit patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, no large-scale retrospective real-world data are available. This retrospective study aimed to examine the efficacy and safety of pembrolizumab in multiple facilities.
Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. [2023]To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab-RT in patients with locally advanced-squamous cell carcinoma of head and neck (LA-SCCHN).
Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. [2019]There are few effective treatment options for patients with recurrent or metastatic head-and-neck squamous cell carcinoma. Pembrolizumab showed antitumour activity and manageable toxicity in early-phase trials. We aimed to compare the efficacy and safety of pembrolizumab versus standard-of-care therapy for the treatment of head-and-neck squamous cell carcinoma.
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
A Phase I trial of prolonged administration of lovastatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or of the cervix. [2013]Squamous cell carcinomas of the head and neck (HNSCC) and of the cervix (CC) are particularly sensitive to the apoptotic effects of lovastatin in vitro. In this Phase I study, the safety and maximum related dose (MTD) of lovastatin was evaluated in these specific clinical settings. This was a Phase I open-label study to determine the recommended Phase II dose (RPTD) of lovastatin in advanced HNSCC or CC. This study involved a dose and duration escalation of lovastatin starting at 5/mg/kg/day x 2 weeks, every 21 days, until the MTD was reached. Plasma samples were collected for pharmacokinetic analysis. All 26 patients enrolled were evaluable. Dose-limiting toxicity (DLT) consisting of reversible muscle toxicity was seen at 10 mg/kg/day x 14 days. Toxicity may be related to relative renal insufficiency. The MTD was determined to be 7.5 mg/kg/day x 21 days, every 28 days. The low lipid levels experienced on study did not translate into adverse events. Biologically relevant plasma lovastatin levels were obtained. No objective responses were seen but the median survival of patients on study was 7.5 months (mean 9.2 +/- 1.5 months). Stable disease (SD) for more than 3 months was seen in 23% of patients. One patient achieved SD and clinical benefit for 14 months on study and a further 23 months off treatment. The disease stabilisation rate of 23% seen in these end-stage patients is encouraging. We conclude that the administration of lovastatin at 7.5 mg/kg/day for 21 consecutive days on a 28-day schedule is well tolerated in patients with good renal function and warrants further clinical evaluation.
Statin drugs enhance responses to immune checkpoint blockade in head and neck cancer models. [2023]Anti-PD-1 immune checkpoint blockade is approved for first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but few patients respond. Statin drugs (HMG-CoA reductase inhibitors) are associated with superior survival in several cancer types, including HNSCC. Emerging data suggest that manipulation of cholesterol may enhance some aspects of antitumor immunity.