Clinical Trials /

Ficlatuzumab w/wo Cetuximab in Patients w/Cetuximab-Resistant, Recurrent or Metastatic Head/Neck Squamous Cell Carcinoma

NCT03422536

Description:

This randomized phase II trial studies how well ficlatuzumab with or without cetuximab work in treating patients with head and neck squamous cell carcinoma that has come back or spread to other places in the body and resistant to cetuximab treatment. Monoclonal antibodies, such as ficlatuzumab and cetuximab, may block growth signals that lets a tumor cell survive and reproduce, and helps the immune system recognize and fight head and neck squamous cell carcinoma.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Head and Neck Squamous Cell Carcinoma of Unknown Primary
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ficlatuzumab With or Without Cetuximab in Treating Patients With Cetuximab-Resistant, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
  • Official Title: A Randomized, Phase II Study of Ficlatuzumab With or Without Cetuximab in Patients With Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 1710965268
  • SECONDARY ID: NCI-2017-02209
  • SECONDARY ID: AV-299-17-117i
  • SECONDARY ID: 1710965268
  • SECONDARY ID: P30CA023074
  • NCT ID: NCT03422536

Conditions

  • Head and Neck Basaloid Carcinoma
  • Recurrent Head and Neck Squamous Cell Carcinoma
  • Recurrent Oropharyngeal Squamous Cell Carcinoma
  • Squamous Cell Carcinoma of Unknown Primary Origin
  • Stage IV Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7
  • Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7
  • Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7
  • Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7
  • Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7
  • Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7
  • Stage IVA Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7
  • Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7
  • Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7
  • Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7
  • Stage IVB Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7
  • Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7
  • Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7
  • Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7
  • Stage IVC Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7
  • Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7
  • Head and Neck Cancer
  • Oropharyngeal Cancer
  • HNSCC

Interventions

DrugSynonymsArms
CetuximabChimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux, IMC-C225Arm II (ficlatuzumab, cetuximab)
FiclatuzumabAnti-HGF Monoclonal Antibody SCH900105, AV-299, SCH 900105Arm I (ficlatuzumab)

Purpose

This randomized phase II trial studies how well ficlatuzumab with or without cetuximab work in treating patients with head and neck squamous cell carcinoma that has come back or spread to other places in the body and resistant to cetuximab treatment. Monoclonal antibodies, such as ficlatuzumab and cetuximab, may block growth signals that lets a tumor cell survive and reproduce, and helps the immune system recognize and fight head and neck squamous cell carcinoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the efficacy of ficlatuzumab, with or without concurrent cetuximab, in patients
      with cetuximab-resistant, recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)
      as measured by progression-free survival (PFS).

      SECONDARY OBJECTIVES:

      I. To describe toxicity and patient-reported quality of life. II. To evaluate response rate
      and overall survival in both treatment arms. III. To evaluate the relationship between
      clinical outcomes (PFS, response rate [RR]) and candidate tumoral, genomic, peripheral, and
      immune biomarkers, including: HGF/cMet, EGFR/EGFR, and EGFR/HER2 dimers; mutations in PIK3CA,
      PTEN, and HRAS; peripheral serum biomarkers including VeriStrat, HGF, soluble HGF, and IL6;
      peripheral lymphocyte populations; archived and baseline immune infiltrate.

      OUTLINE: Patients are randomized into 1 of 2 arms.

      ARM I: Patients receive ficlatuzumab intravenously (IV) over 30-60 minutes every 2 weeks in
      the absence of disease progression or unaccepted toxicity. Courses repeat every 4 weeks in
      the absence of disease progression or unacceptable toxicity.

      ARM II: Patients receive cetuximab IV over 60 -120 minutes and ficlatuzumab IV over 30-60
      minutes every 2 weeks in the absence of disease progression or unaccepted toxicity. Courses
      repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (ficlatuzumab)ExperimentalPatients receive ficlatuzumab IV over 30-60 minutes every 2 weeks in the absence of disease progression or unaccepted toxicity. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
  • Ficlatuzumab
Arm II (ficlatuzumab, cetuximab)ExperimentalPatients receive cetuximab IV over 60 -120 minutes and ficlatuzumab IV over 30-60 minutes every 2 weeks in the absence of disease progression or unaccepted toxicity. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
  • Ficlatuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically confirmed HNSCC from any primary site; basaloid,
             poorly differentiated, and undifferentiated carcinoma histologies will be accepted;
             nasopharyngeal carcinoma, World Health Organization (WHO) type I and II (keratinizing,
             non-Epstein-Barr virus [EBV] positive), will be included; paranasal sinus, lip and
             external auditory canal sites will be included; squamous cell carcinoma of unknown
             primary, clearly related to the head and neck, will be included

          -  Recurrent/metastatic disease, fulfilling at least one of the criteria defined below:

               -  Incurable disease as assessed by surgical or radiation oncology

               -  Metastatic (M1) disease

               -  Persistent or progressive disease following curative-intent radiation, and not a
                  candidate for surgical salvage due to incurability or morbidity; patients who
                  decline radical surgery are eligible

          -  For patients with oropharyngeal primary site or unknown primary site only: tumoral
             human papillomavirus (HPV) status must be known, as established by the local site;
             acceptable standards include p16 immunohistochemistry (where a tumor is classified as
             p16-positive when showing diffuse nuclear and cytoplasmic staining in at least 70% of
             tumor cells) and/or assessment of HPV deoxyribonucleic acid (DNA)

          -  Patients must be cetuximab-resistant by fulfilling at least one of the criteria
             defined below:

               -  Disease persistence or recurrence within 6 months of completing definitive
                  radiotherapy for locally advanced disease; radiation must have included
                  concurrent cetuximab; induction chemotherapy, if given, may or may not have
                  included cetuximab

               -  Disease progression during, or within 6 months, of cetuximab treatment in the
                  recurrent/metastatic setting

               -  Prior cetuximab exposure may have occurred in any line of therapy (first line,
                  second line, etc.) and cetuximab is not required to be the most recent therapy
                  received

          -  Patients must be platinum-resistant or platinum-ineligible by fulfilling at least one
             of the criteria defined below:

               -  Disease persistence or recurrence within 6 months of completing definitive
                  radiotherapy for locally advanced disease, where platinum chemotherapy was
                  administered as a component of induction and/or concurrent systemic treatment

               -  Disease progression during, or within 6 months, of treatment with platinum
                  chemotherapy (eg. carboplatin or cisplatin) in the recurrent/metastatic setting

               -  The patient is not an acceptable candidate for platinum chemotherapy due to
                  medical comorbidities, in the judgment of the local investigator

               -  Prior platinum exposure may have occurred in any line of therapy (first line,
                  second line, etc.) and is not required to be the most recent therapy received

          -  Prior exposure to immunotherapy, including anti-PD1/PDL1, anti-CTLA4, anti-tumor
             necrosis factor receptor (TNFR) antibodies or other investigational immunotherapies,
             is acceptable

          -  Eastern Cooperative Oncology Group performance status 0-1 at time of informed consent

          -  Patients must consent to a research biopsy of tumor tissue at baseline, for conduct of
             correlative studies; archived biopsy material may only be substituted only if no
             interval anti-cancer systemic therapy has been administered

          -  Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria,
             version 1.1

          -  Absolute neutrophil count (ANC) >= 1500/mm^3 (measured within 28 days of registration)

          -  Platelet count (PLT) >= 75,000/mm^3 (measured within 28 days of registration)

          -  Creatinine clearance >= 40 ml/min as determined by 24-hour collection or estimated by
             the Cockcroft-Gault formula (measured within 28 days of registration)

          -  Serum bilirubin =< 1.5 times upper-limit of normal (ULN) (measured within 28 days of
             registration)

          -  AST (aspartate aminotransferase) and ALT (alanine aminotransferase) =< 3 times ULN
             (measured within 28 days of registration)

          -  No prior severe infusion reaction to cetuximab or a monoclonal antibody

          -  Written informed consent must be obtained from all patients prior to beginning
             therapy; patients should have the ability to understand and the willingness to sign a
             written informed consent document

          -  If a woman of childbearing potential, documentation of negative pregnancy within 14
             days prior to registration; a negative pregnancy test must also be confirmed within 3
             days of the first dose of ficlatuzumab; sexually active women of childbearing
             potential must agree to use adequate contraceptive measures, while on study and for 30
             days after the last dose of study drug; all fertile female subjects (and their
             partners) must agree to use a highly effective method of contraception; effective
             birth control includes (a) intrauterine device (IUD) plus one barrier method; or (b) 2
             barrier methods; effective barrier methods are male or female condoms, diaphragms, and
             spermicides (creams or gels that contain a chemical to kill sperm)

        Exclusion Criteria:

          -  Nasopharyngeal primary site, if WHO type III (non-keratinizing and EBV-positive as
             established at the local site)

          -  History of severe allergic or anaphylactic reactions or hypersensitivity to
             recombinant proteins or excipients in the investigational agent

          -  Prior treatment with an hepatocyte growth factor (HGF)/cMet inhibitor such as
             rilotumumab, crizotinib, MetMAb, or ARQ197

          -  Uncontrolled central nervous system (CNS) metastases, including leptomeningeal
             metastases, are not allowed; subjects with previously treated brain metastases will be
             allowed if the brain metastases have been stable without steroid treatment for at
             least 2 weeks (radiotherapy or surgery)

          -  Failure to recover to grade 1 or baseline from all toxic effects of previous
             chemotherapy, radiation therapy, biologic therapy, immunotherapy, and/or experimental
             therapy, with the exception of: alopecia, grade =< 2 peripheral neuropathy, grade =< 2
             cetuximab-related rash or other skin changes, hypomagnesemia (acceptable values
             detailed below), hypokalemia (acceptable values detailed below), and the acceptable
             hematologic values summarized above; a washout period of 2 weeks from prior cetuximab
             is required; a washout period of 3 weeks from any prior cytotoxic chemotherapy,
             targeted therapy, immunotherapy or investigational drug is required

          -  Significant pulmonary disease, including pulmonary hypertension or interstitial
             pneumonitis

          -  Decreased serum albumin < 30 g/L (< 3 g/dL)

          -  Peripheral edema >= grade 2 per National Cancer Institute (NCI)-Common Terminology
             Criteria for Adverse Events (CTCAE) version 4.0

          -  Significant electrolyte imbalance prior to enrollment (note that patients may be
             supplemented to achieve acceptable electrolyte values):

               -  Hypomagnesemia < 1.2 mg/dL or 0.5 mmol/L

               -  Hypocalcemia < 8.0 mg/dL or 2.0 mmol/L

               -  Hypokalemia < 3.0 mmol/L

          -  Significant cardiovascular disease, including:

               -  Cardiac failure New York Heart Association (NYHA) class III or IV

               -  Myocardial infarction, severe or unstable angina within 6 months prior to study
                  day 1

               -  History of serious ventricular arrhythmia (i.e., ventricular tachycardia or
                  ventricular fibrillation)

               -  Cardiac arrhythmia requiring anti-arrhythmic medication(s); note that
                  beta-blockers, calcium channel blockers, and digoxin administered for the purpose
                  rate control of supraventricular tachycardia, including atrial fibrillation and
                  atrial flutter, are not classified as anti-arrhythmic medications for purposes of
                  trial eligibility

          -  Significant thrombotic or embolic events within 4 weeks prior to study day 1;
             significant thrombotic or embolic events include but are not limited to stroke or
             transient ischemic attack (TIA); catheter-related thrombosis is not a cause for
             exclusion; diagnosis of deep vein thrombosis or pulmonary embolism is allowed if it
             occurred > 4 weeks prior to study day 1 and the patient is asymptomatic and stable on
             anti-coagulation therapy

          -  Any other medical condition (eg, alcohol abuse) or psychiatric condition that, in the
             opinion of the investigator, might interfere with the subject?s participation in the
             trial or interfere with the interpretation of trial results

          -  History of second malignancy within 2 years prior to study day 1 (except for excised
             and cured non-melanoma skin cancer, carcinoma in situ of breast or cervix, superficial
             bladder cancer, stage I differentiated thyroid cancer that is resected or observed, or
             pT1a /pT1b prostate cancer comprising < 5% of resected tissue with normal prostate
             specific antigen (PSA) since resection, or cT1a/cT1b prostate cancer treated with
             brachytherapy or external beam radiation therapy with normal PSA since radiation)

          -  Major surgery within 6 weeks prior to study day 1 (subjects must have completely
             recovered from any previous surgery prior to study day 1)

          -  Active infection requiring systemic antibiotics or antifungals within 7 days prior to
             first dose of study drug; exception: tetracycline family antibiotics (tetracycline,
             doxycycline, minocycline) administered for the management of cetuximab-related rash
             may be continued per the investigator?s judgment

          -  Human immunodeficiency virus (HIV)-positive patients receiving combination
             anti-retroviral therapy are excluded from the study; appropriate studies will be
             undertaken in patients receiving combination anti-retroviral therapy when indicated;
             Note: HIV testing is not required for entry into this protocol

          -  Women must not be pregnant or breastfeeding; pregnant women are excluded from this
             study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:From the date of randomization until the date of progression or death, assessed up to 2 years
Safety Issue:
Description:Will be estimated for each arm using a Kaplan-Meier curve.

Secondary Outcome Measures

Measure:Biomarker analysis
Time Frame:Up to 2 years
Safety Issue:
Description:Will evaluate the relationship between clinical outcomes (progression free survival, response rate) and candidate tumoral, genomic, peripheral, and immune biomarkers, including: HGF/cMet, EGFR/EGFR, and EGFR/HER2 dimers; mutations in PIK3CA, PTEN, and HRAS; peripheral serum biomarkers including VeriStrat, HGF, soluble HGF, and IL6; peripheral lymphocyte populations; archived and baseline immune infiltrate. The relationship between progression-free survival and the candidate biomarkers will be assessed using Cox proportional hazards models. The relationship with clinical response will be assess
Measure:Change in quality of life
Time Frame:Pre-study (within 4 weeks of study registration) and Week 4, Cycle 2 of Intervention
Safety Issue:
Description:Will be assessed by Foundation for the Accreditation of Cellular Therapy Head and Neck Questionnaire.
Measure:Incidence of adverse events
Time Frame:Up to 2 years
Safety Issue:
Description:The proportion of dose limiting toxicities in each dosing cohort will be reported, as will the proportion of adverse events in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events version 4 grading criteria. Will be tabulated and reported with 95% exact confidence intervals.
Measure:Overall survival
Time Frame:From the date of randomization until the date of death, assessed up to 2 years
Safety Issue:
Description:Will be estimated for each arm using a Kaplan-Meier curve.
Measure:Response rate
Time Frame:Up to 2 years
Safety Issue:
Description:Will be assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Will be tabulated and reported with 95% exact confidence intervals.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Arizona

Trial Keywords

  • Head and Neck Cancer
  • Oropharyngeal Cancer
  • Squamous Cell Carcinoma
  • lip carcinoma
  • oral cavity carcinoma
  • HNSCC
  • Head and Neck Squamous Cell Carcinoma
  • AVEO

Last Updated

February 2, 2018