Lenvatinib Mesylate and Cetuximab in Treating Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma or Cutaneous Squamous Cell Carcinoma
- Histological or cytologic diagnosis of squamous cell cancer
- Clinical diagnosis of squamous cell cancer of the head and neck (non-nasopharynx primary tumors: oral cavity, oropharynx, hypopharynx, larynx, and sinonasal) or skin
- HNSCC and cSCC cannot be curable by surgery and/or radiation therapy
- Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, which includes locoregional lesions (not amenable to curative surgery and/or radiation) and distant metastatic lesions
- Blood pressure < 150/90 at screening with or without antihypertensive medications and no change in antihypertensive medications within 1 week prior to initiation of treatment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Adequate renal function as evidenced by calculated creatinine clearance > 30 ml/min according to the Cockcroft and Gault formula or by 24 hour urine creatinine clearance
- Bilirubin < 1.5 x upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x upper limit of normal (ULN) (< 5 x ULN if subject has liver metastases [mets])
- Platelets > 100,000
- Hemoglobin > 9 gm/dl
- Absolute neutrophil count > 1200
- Adequate archival tissue to perform molecular analysis through Memorial Sloan Kettering (MSK)-Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) if MSK-IMPACT has not been performed previously on the patient's tumor; if MSK-IMACT has not been previously performed and adequate archival tissue is not available, a patient should be agreeable to a pre-treatment biopsy
- Prior grade 3 hypersensitivity to cetuximab requiring discontinuation * An exception is for a patient who could subsequently receive cetuximab without a reaction
- Prior lenvatinib
- Major surgery within 2 weeks of first dose of lenvatinib
- Metastatic brain or leptomeningeal tumors (treated metastatic brain or leptomeningeal tumors are allowed)
- Anticancer treatment (e.g., radiation therapy, chemotherapy) within 21 days of first dose * An exception is cetuximab treatment, which can be received within 21 days of the first treatment on study
- No prior palliative radiation to a target lesion is allowed, unless there is clear biopsy proven progression following radiation. Note, prior radiations to a non-target lesion is allowed
- Subjects having a spot urine protein:creatinine ratio of > 1 will undergo 24-hour collection for quantitative assessment of proteinuria. If urine protein > 1 gram/24 hours, the subject will be ineligible
- Significant cardiovascular impairment within 6 months as defined as (1) congestive heart failure greater than New York Heart Association class II, (2) unstable angina, (3) myocardial infarction; (4) stroke, (5) symptomatic cardiac arrhythmia
- On electrocardiogram, corrected QT (QTc) interval > 500 msec
- Active infection requiring systemic therapy
- Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to first dose of lenvatinib
- Other active malignancy except for basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or bladder
- Women who are breast feeding or pregnant * Men or women of reproductive potential who are not willing to employ effective birth control from screening to 30 days after the last dose of study drugs; the definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate For a female patient to be considered as not of child bearing potential, she should fulfill one of the following: * Post-menopausal women, defined as either women aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments, or, women under 50 years old who have been amenorrhoeic for at least 12 months following the cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in the postmenopausal range for the institution Or * Have documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy (but not tubal ligation)
- Evidence of clinically significant disease (e.g., cardiovascular, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator could affect the subject safety or interfere with the study assessments
I. To determine the maximum tolerated dose (MTD) of lenvatinib mesylate (lenvatinib) that can be used in combination with cetuximab.
I. To assess the safety profile of the combination of lenvatinib and cetuximab.
I. To assess the objective response rate of the combination of lenvatinib and cetuximab separately in patients with recurrent (R)/metastatic (M) head and neck squamous cell carcinoma (HNSCC) and in patients with R/M cutaneous squamous cell carcinoma (cSCC).
II. To assess progression-free survival in patients with R/M HNSCC and in patients with R/M cSCC treated with the combination of lenvatinib and cetuximab.
III. To preliminarily investigate molecular tumor biomarkers in HNSCC and cSCC that correlate to response to the combination of lenvatinib and cetuximab.
OUTLINE: This is a dose-escalation study of lenvatinib mesylate.
Patients receive lenvatinib mesylate orally (PO) once daily (QD) on days 1-28 and cetuximab intravenously (IV) over 120 minutes on days 1, 8, 15 and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days.
Trial Phase Phase I
Trial Type Treatment
Memorial Sloan Kettering Cancer Center
Lara Ann Dunn
- Primary ID 17-635
- Secondary IDs NCI-2018-00991
- Clinicaltrials.gov ID NCT03524326