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 ethylenediaminotetraacetic 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 because of their poor prognosis and because they often develop progressive
neurologic dysfunction that would confound the evaluation of neurologic and other
adverse events; 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