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

May 8, 2025 updated by: Memorial Sloan Kettering Cancer Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memoral Sloan Kettering Basking Ridge
      • Middletown, New Jersey, United States, 07748
        • Memoral Sloan Kettering Monmouth
      • Montvale, New Jersey, United States, 07645
        • Memorial Sloan Kettering Bergen
    • New York
      • Commack, New York, United States, 11725
        • Memorial Sloan Kettering Cancer Center @ Commack
      • Harrison, New York, United States, 10604
        • Memoral Sloan Kettering Westchester
      • New York, New York, United States, 10021
        • Memorial Sloan - Kettering Cancer Center
      • Uniondale, New York, United States, 11553
        • Memorial Sloan Kettering Nassau

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional 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
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
24 mg oral daily
Other Names:
  • Level 0 Lenvatinib
Drug: Lenvatinib Pill
20 mg oral daily
Other Names:
  • Level -1 Lenvatinib
Drug: Lenvatinib Pill
14 mg oral daily
Other Names:
  • Level -2 Lenvatinib
Drug: Cetuximab
400mg/m2 IV, then 500mg/m2 IV weekly
Drug: Lenvatinib Pill
10 mg oral daily
Other Names:
  • Level -3 Lenvatinib
Drug: Lenvatinib Pill
4 mg oral daily
Other Names:
  • Level -4 Lenvatinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose of Lenvatinib when combined with Cetuximab
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Investigators

  • Principal Investigator: Lara Dunn, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 30, 2018

Primary Completion (Actual)

October 13, 2022

Study Completion (Actual)

October 13, 2022

Study Registration Dates

First Submitted

May 1, 2018

First Submitted That Met QC Criteria

May 2, 2018

First Posted (Actual)

May 14, 2018

Study Record Updates

Last Update Posted (Actual)

May 13, 2025

Last Update Submitted That Met QC Criteria

May 8, 2025

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-635

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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