Phase II Randomized Trial of the Combination of Cetuximab and Sorafenib or Single Agent Cetuximab
Condition: Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Laryngeal Neoplasms; Oropharyngeal Neoplasms; Carcinoma, Verrucous; Squamous Cell Carcinoma of Head and Neck; Salivary Gland Neoplasms; Nasopharyngeal Carcinoma; Paranasal Sinus Neoplasms; Neoplasms, Unknown Primary; Tongue Neoplasms; Laryngeal Diseases; Recurrence
Intervention: cetuximab; placebo; sorafenib tosylate; laboratory biomarker analysis; quality-of-life assessment
Intervention description: Given IV; Given orally; Given orally; Correlative studies; Ancillary studies
Intervention MeSH terms: Antineoplastic Agents, Immunological; Cetuximab; Sorafenib; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 55.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some
      block the ability of tumor cells to grow and spread. Others find tumor cells and help kill
      them or carry tumor-killing substances to them. Sorafenib tosylate may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow
      to the tumor. It is not yet known whether cetuximab is more effective when given alone or
      together with sorafenib tosylate in treating patients with head and neck cancer. This
      randomized phase II trial is studying cetuximab to see how well it works when given together
      with or without sorafenib tosylate in treating patients with refractory, recurrent, and/or
      metastatic head and neck cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with recurrent, refractory or metastatic squamous cell carcinoma of oral
             cavity, oropharynx and larynx, hypopharynx or paranasal sinus, head and neck unknown
             primary or nasopharyngeal carcinoma WHO type 1; patients with recurrent, refractory or
             metastatic squamous cell carcinoma of oral cavity, oropharynx and larynx, hypopharynx
             or paranasal sinus, head and neck unknown primary or nasopharyngeal carcinoma WHO type
             1; patients may have had up to 1 prior palliative chemotherapy for recurrent or
             metastatic disease; please note that chemotherapy given as part of a regimen for
             curative intent for recurrent disease does not count as "prior chemotherapy;" patients
             must not presently be candidates for curative therapy

          -  ECOG performance status 0, 1 or 2

          -  Hemoglobin >= 9.0/dl

          -  Absolute-neutrophil count (ANC) >= 1500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Total bilirubin =< 1.5 x ULN

          -  ALT and AST =< 2.5 x ULN (=< 5 x ULN for patients with liver involvement)

          -  INR < 1.5 or a PT and PTT within normal limits

          -  Creatinine =< 1.5 x ULN

          -  If primary therapy was given for curative intent, at least 4 weeks must have elapsed
             after completion of primary therapy prior to enrollment on this clinical trial;
             however, toxicities from prior treatment must have resolved to grade 1 or less

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days prior to the start of the treatment; women of childbearing potential and
             men must agree to use adequate contraception prior to study entry and for the duration
             of study participation (i.e, a hormonal contraceptive, intra-uterine device, diaphragm
             with spermicide, condom with spermicide, or abstinence) for the duration of the study
             and for a minimum of 3 months following the last dose of chemotherapy; male subject
             agrees to use an acceptable method for contraception for the duration of the study and
             for a minimum of 3 months following the last dose of chemotherapy

          -  Patients must have a measurable disease defined by RECIST criteria

          -  Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care, with the understanding that consent may be withdrawn
             by the subject at any time without prejudice to future medical care; patients or their
             legal representatives must be able to read, understand and provide informed consent to
             participate in the trial

        Exclusion Criteria:

          -  Prior treatment with sorafenib or cetuximab

          -  Patients with active clinically significant infection or with a fever >= 38.5º C
             within 3 days of the first scheduled day of protocol treatment

          -  History of prior malignancy within the past 3 years except for curatively treated
             basal cell carcinoma and squamous cell carcinoma of the skin, CIN or localized
             prostate cancer with a current PSA < 1.0 mg/dL on 2 successive evaluations at least 3
             months apart, with the most recent evaluation within 4 weeks of study entry

          -  Patients with known hypersensitivity to sorafenib or cetuximab

          -  Prior severe infusion reaction to a monoclonal antibody

          -  History of hand-foot syndrome

          -  Pregnant or lactating; sexually active women of childbearing potential must use an
             effective method of birth control during the course of the study, in a manner such
             that risk of failure is minimized

          -  Known untreated brain metastasis; patients with neurological symptoms must undergo a
             CT scan/MRI of the brain to exclude brain metastasis or progression of brain
             metastasis; patients with treated brain metastasis are eligible for study as long as
             no evidence of progression of CNS disease; hemorrhagic brain metastases are not
             allowed on study

          -  Uncontrolled comorbid illness

          -  Patients with HIV who are taking antiretroviral mediations will be excluded because of
             the potential interactions of anti-retroviral medications with these agent; however,
             given the potential immune modulating effects of sorafenib, investigators should still
             be very cautious about placing HIV positive patients on this trial as the effects of
             these medications on the HIV virus itself are not know

          -  History of allogeneic transplant

          -  Patient has received other investigational drugs within 28 days before enrollment

          -  Cardiac disease: congestive heart failure > class II NYHA; patients must not have
             unstable angina (anginal symptoms at rest) or new onset angina (began within the last
             3 months) or myocardial infarction within the past 6 months; significant history of
             uncontrolled cardiac disease; i.e., uncontrolled hypertension (defined as defined as
             systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal
             medical management), uncontrolled congestive heart failure, and cardiomyopathy with
             decreased ejection fraction will also be excluded from study; cardiac ventricular
             arrhythmias requiring anti-arrhythmic therapy will also be excluded from study

          -  Thrombotic or embolic events such as a cerebrovascular accident including transient
             ischemic attacks within the past 6 months

          -  Pulmonary hemorrhage/bleeding event > CTCAE grade 2 within 4 weeks of first dose of
             study drug

          -  Any other hemorrhage/bleeding event > CTCAE grade 3 within 4 weeks of first dose of
             study drug

          -  Tumor that invades the carotid artery as shown unequivocally by imaging studies

          -  Serious non-healing wound, ulcer, or bone fracture

          -  Evidence or history of bleeding diathesis or coagulopathy

          -  Major surgery, open biopsy or significant traumatic injury within 4 weeks of first
             study drug

          -  Use of St. John's Wort or rifampin (rifampicin)

          -  Use of the following medications will not be allowed within 4 weeks prior to
             enrollment on the study and during the study: ketoconazole, itraconazole, ritonavir,
             cyclosporine, carbamazepine, phenytoin, phenobarbital; products containing grapefruit
             juice will not be allowed while on study

          -  Known or suspected allergy to sorafenib or any agent given in the course of this trial

          -  Any malabsorption problem

          -  Known HIV positive patients will be excluded from trial due to the potential immune
             modulation that these agents may cause