Ficlatuzumab w/wo Cetuximab in Patients w/Cetuximab-Resistant, Recurrent or Metastatic Head/Neck Squamous Cell Carcinoma
Condition: 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 Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IV Oropharyngeal Squamous Cell Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma; Head and Neck Cancer; Oropharyngeal Cancer; HNSCC; Stage IV Lip and Oral Cavity Squamous Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Oropharyngeal Neoplasms; Recurrence
Intervention: Cetuximab; Ficlatuzumab
Intervention description: Given IV; Given IV
Intervention MeSH terms: Antineoplastic Agents, Immunological; Cetuximab; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 78.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Head and Neck Cancer; Oropharyngeal Cancer; Squamous Cell Carcinoma; lip carcinoma; oral cavity carcinoma; HNSCC; Head and Neck Squamous Cell Carcinoma; AVEO

Summary:

      This randomized phase II trial studies how well ficlatuzumab with or without cetuximab works
      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.
    

Eligibility criteria:

        Inclusion Criteria:

        - Patients must have histologically confirmed HNSCC from any primary site, except
        nasopharyngeal if World Health Organization (WHO) Type III (non-keratinizing and
        Epstein-Barr virus (EBV)-positive)).

        Eligible histologies include:

          -  Basaloid, poorly differentiated, and undifferentiated carcinoma histologies.

          -  Nasopharyngeal carcinoma, WHO Type I and II (keratinizing, non-EBV positive).

          -  Paranasal sinus, lip and external auditory canal sites.

          -  Squamous cell carcinoma of unknown primary, clearly related to the head and neck.

        Note: Documentation of primary site diagnosis must be submitted with the registration
        request.

          -  Patients must have recurrent and/or 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. Note: Patients who
             decline radical surgery are eligible.

          -  For patients with oropharyngeal primary site or unknown primary site only: Patients
             must have known tumoral HPV status (p16). (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 DNA.) Note: For these subjects, documentation of p16 status must be submitted with
             the registration packet.

          -  Patients must be cetuximab-resistant by fulfilling at least one of the two criteria
             defined below:

          -  Disease persistence or recurrence within 6 months of completing definitive
             radiotherapy with concurrent cetuximab for locally advanced disease. Induction
             chemotherapy, if given, may or may not have included cetuximab.

          -  Disease progression during, or within 6 months, of cetuximab treatment in the
             recurrent and/or metastatic setting.

        Note: Prior cetuximab 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.

          -  Patients must be platinum-resistant or platinum-ineligible by fulfilling at least one
             of the three 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 (e.g., carboplatin or cisplatin) in the recurrent and/or metastatic
             setting.

          -  The patient is not an acceptable candidate for platinum chemotherapy due to medical
             comorbidities, in the judgment of the local investigator.

        Note: 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.

        - Patients must have prior exposure to an anti-PD1 (programmed cell death protein 1) or
        anti-PDL1 (programmed cell death ligand 1) monoclonal antibody (mAb), if eligible for
        immunotherapy in the judgment of the local investigator.

        Note: Prior exposure to investigational immunotherapies, including anti-CTLA4 (cytotoxic
        T-lymphocyte-associated antigen 4), anti-OX40, anti-CD40 (cluster of differentiation 40),
        anti-CD27, anti-TNFR (tumor necrosis factor receptor) antibodies or other investigational
        immunotherapies, is acceptable.

          -  Patients must have Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 at
             time of informed consent (see Appendix B).

          -  Patients must be age ≥ 18 years.

          -  Patients must consent to a research biopsy of tumor tissue at baseline, for conduct of
             correlative studies. In cases where a fresh biopsy is not feasible (i.e., if an
             accessible tumor site cannot be biopsied with acceptable clinical risk), archival
             tissue may be submitted instead, after discussion with and approval by the
             Sponsor-Investigator.

          -  Patients must have measurable disease per Response Evaluation Criteria in Solid Tumors
             (RECIST) criteria, version 1.1 (see section 6) per scan within 28 days prior to
             registration.

          -  Patients must have adequate electrolytes, liver, renal, and hematology function as
             defined below within 28 days of registration:

          -  Absolute neutrophil count (ANC) ≥ 1500/mm3

          -  Platelet count (PLT) ≥ 75,000/mm3

          -  Creatinine clearance ≥ 30 mL/min per estimated by the Cockraft-Gault formula:

          -  Calculated Creatinine Clearance = [(140-age) X (actual body weight in kg) X (0.85 if
             female)]/(72 X serum creatinine)

             * Total bilirubin ≤ 1.5 times upper-limit of normal (ULN)

          -  AST (aspartate aminotransferase) ≤ 3 times ULN

          -  ALT (alanine aminotransferase) ≤ 3 times ULN

          -  Magnesium ≥ 1.2 mg/dL or 0.5 mmol/L

          -  Corrected Calcium ≥ 8.0 mg/dL or 2.0 mmol/L

          -  Potassium ≥ 3.0 mmol/L (Note: Patients may be supplemented to achieve acceptable
             electrolyte values.)

          -  Serum albumin ≥ 25 g/L (≥ 2.5 g/dL)

          -  Patients must sign written informed consent prior to beginning study screening
             procedures. Patients must have the ability to understand and the willingness to sign a
             written informed consent document.

          -  Women of child-bearing potential (WOCBP) must agree to have a pregnancy test within 14
             days prior to registration and a repeated test within 3 days of the first dose of
             ficlatuzumab.

          -  Patients must agree to use highly effective contraceptive measures while on study and
             for 60 days after the last dose of study drug. This includes: Men of reproductive
             potential AND women of childbearing potential.

          -  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 HGF/cMet inhibitor such as rilotumumab, crizotinib, MetMAb, or
             tivantinib (ARQ197).

          -  Uncontrolled central nervous system (CNS) metastases, including leptomeningeal
             metastases, are not allowed.

        Note: 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 in the exclusion criteria below),

          -  Hypokalemia (acceptable values detailed in the exclusion criteria below), and

          -  The acceptable ANC and PLT inclusion criteria values above.

          -  Treatment with cetuximab 2 weeks prior to the first dose of study drug. A washout
             period of 2 weeks from prior cetuximab is required if applicable.

          -  Treatment with cytotoxic chemotherapy, targeted therapy, immunotherapy or
             investigational drug 3 weeks prior to the first dose of study drug. A washout period
             of 3 weeks from any prior cytotoxic chemotherapy, targeted therapy, immunotherapy or
             investigational drug is required, if applicable.

          -  Significant underlying pulmonary disease, including pulmonary hypertension or
             interstitial pneumonitis.

          -  Peripheral edema ≥ Grade 2 per NCI-CTCAE version 4.0.

          -  Significant cardiovascular disease, including:

          -  Cardiac failure New York Heart Association (NYHA) class III or IV.

          -  Myocardial infarction within 6 months prior to registration.

          -  Severe or unstable angina within 6 months prior to registration.

          -  History of serious ventricular arrhythmia (i.e., ventricular tachycardia or
             ventricular fibrillation).

          -  Cardiac arrhythmia requiring anti-arrhythmic medication(s). (Beta-blockers, calcium
             channel blockers, and digoxin administered for the purpose of 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 28 days prior to registration.
             (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 > 28 days prior to registration and the patient is asymptomatic and stable on
             anti-coagulation therapy.)

          -  Any other medical condition (e.g., alcohol abuse) or psychiatric condition that, in
             the opinion of the local 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 registration except:

          -  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,

          -  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.

          -  Not completely recovered from any previous surgery. Note: Complete recovery is in the
             opinion of the treating investigator. Consult the Sponsor-Investigator, if needed.

          -  Active systemic infection requiring systemic antibiotics or antifungals within 7 days
             prior to first dose of study drug, except tetracycline family antibiotics
             (tetracycline, doxycycline, minocycline) administered for the management of
             cetuximab-related rash may be continued per the Investigator's judgment.

        Note: Active topical infections (for example oral thrush) do not exclude a subject even if
        treated with systemic antibiotics or systemic antifungals.

          -  History of severe infusion reaction to cetuximab or a monoclonal antibody.

          -  Known to be Human immunodeficiency virus (HIV) positive. Note: HIV testing is not
             required for entry into this protocol.

          -  Women who are pregnant or breastfeeding. (A negative urine pregnancy test must be
             confirmed within 14 days of registration and repeated within 3 days of the first dose
             of study drug.)