Clinical Trials /

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

NCT03524326

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Skin Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Testing Lenvatinib and Cetuximab in Patients With Advanced Head and Neck Squamous Cell Carcinoma and Cutaneous Squamous Cell Carcinoma
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 17-635
  • NCT ID: NCT03524326

Conditions

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

Interventions

DrugSynonymsArms
Lenvatinib PillLevel 0 LenvatinibHead and Neck Squamous or Cutaneous Squamous Cell Carcinoma
Lenvatinib PillLevel -1 LenvatinibHead and Neck Squamous or Cutaneous Squamous Cell Carcinoma
Lenvatinib PillLevel -2 LenvatinibHead and Neck Squamous or Cutaneous Squamous Cell Carcinoma
CetuximabHead and Neck Squamous or Cutaneous Squamous Cell Carcinoma

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Head and Neck Squamous or Cutaneous Squamous Cell CarcinomaExperimentalA 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.
  • Lenvatinib Pill
  • Lenvatinib Pill
  • Lenvatinib Pill
  • Cetuximab

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

          -  For the HNSCC expansion phase, patients who have previously progressed on cetuximab
             are excluded. Previous cetuximab treatment is allowed if no progression occurred on
             this agent.

          -  No prior palliative radiation to a target lesion is allowed. 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose of Lenvatinib when combined with Cetuximab
Time Frame:1 year
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • cetuximab
  • Lenvatinib
  • Memorial Sloan Kettering Cancer Center
  • 17-635

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