Testing Lenvatinib and Cetuximab in Patients With Advanced Head and Neck Squamous Cell Carcinoma and Cutaneous Squamous Cell Carcinoma

Study Overview
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Brief Summary
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This is a phase I study, which tests the safety of different doses of lenvatinib in combination with cetuximab, to see which dose is the safest in people. This study will help find out if lenvatinib and cetuximab is a safe and useful combination for treating patients with HNSCC and cSCC.

Official Title
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A Phase I/Ib Study of Lenvatinib and Cetuximab in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Cutaneous Squamous Cell Carcinoma

Conditions
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Head and Neck Squamous Cell Carcinoma, Cutaneous Squamous Cell Carcinoma, Head and Neck Cancer, Head and Neck Carcinoma

Intervention / Treatment
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* Drug: Lenvatinib Pill
* Drug: Lenvatinib Pill
* Drug: Lenvatinib Pill
* Drug: Cetuximab
* Drug: Lenvatinib Pill
* Drug: Lenvatinib Pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Measureable disease as per RECIST v1.1, 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 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 Adequate liver function as determined by (1) Bilirubin < 1.5 x upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilberts syndrome; (2) ALT and AST < 3 x ULN (<5 x ULN if subject has liver mets) Adequate hematologic function as determined by (1) platelets > 100,000; (2) Hemoglobin > 9 gm/dl; (3) absolute neutrophil count > 1200 Adequate archival tissue to perform molecular analysis through MSK-IMPACT if MSK-IMPACT has not been performed previously on the patients 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 Exclusion Criteria: Prior grade 3 hypersensitivity to cetuximab requiring discontinuation 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. Please see section 9.3.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, 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 sterilisation 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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Head and Neck Squamous or Cutaneous Squamous Cell Carcinoma<br>A 3+3 dose de-escalation design for three dose levels of lenvatinib combined with cetuximab will be used. A DLT will be defined as any toxicities of grade 3 or higher (per CTCAE v4 criteria) felt to be possibly, probably, or definitely related to lenvatinib, as well as grade 4 toxcities related to cetuximab, which occurs within 28 days following the first dose of lenvatinib in combination with cetuximab. | Drug: Lenvatinib Pill<br>* 24 mg oral daily<br>* Other names: Level 0 Lenvatinib;Drug: Lenvatinib Pill<br>* 20 mg oral daily<br>* Other names: Level -1 Lenvatinib;Drug: Lenvatinib Pill<br>* 14 mg oral daily<br>* Other names: Level -2 Lenvatinib;Drug: Cetuximab<br>* 400mg/m2 IV, then 500mg/m2 IV weekly<br>Drug: Lenvatinib Pill<br>* 10 mg oral daily<br>* Other names: Level -3 Lenvatinib;Drug: Lenvatinib Pill<br>* 4 mg oral daily<br>* Other names: Level -4 Lenvatinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of Lenvatinib when combined with Cetuximab |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cetuximab, Lenvatinib, Memorial Sloan Kettering Cancer Center, 17-635