Temsirolimus With or Without Cetuximab in Patients With Recurrent and/or Metastatic Head and Neck Cancer Who Did Not Respond to Previous Therapy
Condition: Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Verrucous Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oral Cavity Verrucous Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Verrucous Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oral Cavity Verrucous Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Carcinoma, Verrucous; Squamous Cell Carcinoma of Head and Neck; Salivary Gland Neoplasms; Recurrence
Intervention: Cetuximab; Laboratory Biomarker Analysis; Temsirolimus
Intervention description: Given IV; Correlative studies; Given IV
Intervention MeSH terms: Sirolimus; Antineoplastic Agents, Immunological; Cetuximab; Temsirolimus; MTOR Inhibitors; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 86.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well giving temsirolimus together with cetuximab works
      compared to temsirolimus alone in treating patients with recurrent and/or metastatic head and
      neck cancer who did not respond to previous therapy. Temsirolimus may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth. 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. It is not yet known whether giving temsirolimus together with cetuximab
      is more effective than giving temsirolimus alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically/cytologically confirmed diagnosis of squamous cell carcinoma of head
             and neck origin not amenable to curative intent therapy; information on prior exposure
             to cetuximab (duration, single agent/combined with chemotherapy/combined with
             radiation, best response, interval prior to study entry) will be collected

          -  Progressive disease by RECIST criteria (or unequivocal clinical progression) on a
             cetuximab based therapy in any line of therapy for recurrent/metastatic disease; prior
             use of cetuximab for recurrent/metastatic disease is defined as palliative intent use
             either alone or in combination with chemotherapy with a minimum of 2 weeks of
             uninterrupted treatment with cetuximab; treatment with cetuximab during radiotherapy
             or chemoradiotherapy is not sufficient

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1

          -  Presence of measurable lesions by RECIST: patients must have measurable disease,
             defined as at least one lesion that can be accurately measured in at least one
             dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques
             or as >= 10 mm with spiral computed tomography (CT) scan

          -  Knowledge of the anatomic site of the original tumor (oropharynx versus
             non-oropharynx) or alternatively human papilloma virus (HPV) status; the trial will
             stratify patients by oropharynx versus non-oropharynx origin; HPV(+) tumors will be
             counted in the oropharynx cohort, HPV(-) tumors in the non-oropharynx cohort; at a
             later point all patients will undergo HPV testing as part of this trial; any widely
             used form of HPV testing is acceptable (including but not limited to HPV in situ
             hybridization [ISH], p16 testing [immunohistochemistry (IHC)], HPV16 testing,
             polymerase chain reaction [PCR], hybrid capture, etc)

          -  Availability of formalin-fixed, paraffin-embedded (FFPE) tissue and blood

               -  FFPE: >=14 slides containing tumor, 18 recommended

                    -  7-10 slides 5 um thick, AND 7-10 slides 10 um thick, and cut with a clean
                       blade (use new blade if possible or clean vigorously to avoid RNA/DNA, RNase
                       contamination)

               -  Blood: two 10 cc ethylenediaminetetraacetic acid (EDTA) purple top tubes (blood);
                  two 2 ml cryovials (serum)

          -  Patients with human immunodeficiency virus (HIV), not requiring highly active
             antiretroviral treatment (HAART) therapy are eligible

          -  Life expectancy of greater than 8 weeks

          -  Leukocytes >= 2,000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin within normal institutional limits (unless proven Gilbert's disease,
             which after principal investigator [PI] approval patient may be included)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 X institutional upper limit of normal

          -  Creatinine within 1.5 X normal institutional limits

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Fasting glucose of =< 120 mg/dl and glycosylated hemoglobin (HbA1c) =< 7.5%

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 2 weeks earlier

          -  Patients may not be receiving any other investigational agents

          -  Patients with known, active brain metastases should be excluded from this clinical
             trial; patients with treated brain metastases stable for >= 12 weeks are eligible

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to temsirolimus or cetuximab

          -  Concurrent life-threatening diseases: patients with diseases which with reasonable
             certainty do not limit life expectancy to 12 months or less are eligible; assessment
             of such concurrent illnesses should be by the principal investigator

          -  Use of strong inhibitors/inducers of CYP3A4 is not permitted

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women are excluded from this study

          -  Breastfeeding should be discontinued if the mother is treated with temsirolimus

          -  HIV-positive patients with normal immune function (CD4 count > 200) are eligible if
             there are no drug interactions with temsirolimus or cetuximab; patients with impaired
             immune function are ineligible due to the risk of additional immunosuppression from
             temsirolimus therapy

          -  Concurrent administration of temsirolimus with vaccinations is to be avoided and a
             14-day window from administration of the vaccine is advised; in emergent situations
             this policy may be revisited by the PI if deemed important for the patient's health

          -  Poorly controlled hyperglycemia (HbA1C > 7.5%) or hyperlipidemia are exclusion
             criteria; hyperglycemia or hyperlipidemia need to be appropriately managed and
             controlled

          -  Concurrent use of warfarin is allowed, but requires close monitoring of prothrombin
             time (PT)/international normalized ratio (INR)

          -  Patients with clinically significant pneumonitis/pulmonary infiltrates unless there is
             a known and treatable cause for the condition