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

NCT ID: NCT03524326

Last Updated: 2025-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-30
• Study Completion Date: 2022-10-13

Brief Summary

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.

Conditions

Head and Neck Squamous Cell Carcinoma; Cutaneous Squamous Cell Carcinoma; Head and Neck Cancer; Head and Neck Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Head and Neck Squamous or Cutaneous Squamous Cell Carcinoma

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.

Group Type: EXPERIMENTAL

Lenvatinib Pill

Intervention Type: DRUG

24 mg oral daily

Lenvatinib Pill

Intervention Type: DRUG

20 mg oral daily

Lenvatinib Pill

Intervention Type: DRUG

14 mg oral daily

Cetuximab

Intervention Type: DRUG

400mg/m2 IV, then 500mg/m2 IV weekly

Lenvatinib Pill

Intervention Type: DRUG

10 mg oral daily

Lenvatinib Pill

Intervention Type: DRUG

4 mg oral daily

Interventions

Lenvatinib Pill

24 mg oral daily

Intervention Type: DRUG

Lenvatinib Pill

20 mg oral daily

Intervention Type: DRUG

Lenvatinib Pill

14 mg oral daily

Intervention Type: DRUG

Cetuximab

400mg/m2 IV, then 500mg/m2 IV weekly

Intervention Type: DRUG

Lenvatinib Pill

10 mg oral daily

Intervention Type: DRUG

Lenvatinib Pill

4 mg oral daily

Intervention Type: DRUG

Other Intervention Names

Level 0 Lenvatinib; Level -1 Lenvatinib; Level -2 Lenvatinib; Level -3 Lenvatinib; Level -4 Lenvatinib

Eligibility Criteria

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 Gilbert"s 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 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

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lara Dunn, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memoral Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Memoral Sloan Kettering Monmouth

Middletown, New Jersey, United States

Memorial Sloan Kettering Bergen

Montvale, New Jersey, United States

Memorial Sloan Kettering Cancer Center @ Commack

Commack, New York, United States

Memoral Sloan Kettering Westchester

Harrison, New York, United States

Memorial Sloan - Kettering Cancer Center

New York, New York, United States

Memorial Sloan Kettering Nassau

Uniondale, New York, United States

Countries

United States

Related Links

http://www.mskcc.org

Memorial Sloan Kettering Cancer Center

Other Identifiers

17-635

Identifier Type: -

Identifier Source: org_study_id