A Phase I/II Study of Temsirolimus + Weekly Paclitaxel + Carboplatin for Recurrent or Metastatic Head and Neck Squamous Cell Cancer (HNSCC)

Inclusion Criteria:

- Patients must have microscopically confirmed head and neck squamous cell carcinoma
(HNSCC), recurrent and/or metastatic.

- Confirmation of HNSCC may be obtained from the primary site or metastatic disease.

- Patients must be at least 18 years of age.

- Karnofsky Performance status must be ≥ 70%.

- Disease must be measurable by RECIST criteria.

- At least 6 weeks must have elapsed from previous radiation therapy. Patient must have
recovered from the acute toxic effects of treatment prior to study enrollment.

- Adequate organ function, as follows:

- Adequate bone marrow reserve: absolute neutrophil count (ANC) ≥ 1.5 X 109/L,
platelets ≥ 100 X 109/L, and hemoglobin ≥ 9 g/dL.

- Hepatic: total bilirubin within normal limits (≤ 1.0 mg/dL); alkaline phosphatase
(AP), aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 X ULN (upper
limit of normal)

- Renal: Serum creatinine ≤ 1.3 mg/dL. Patients with serum creatinine > 1.3 mg/dL may
be eligible if creatinine clearance (CrCl) ≥ 45 mL/min based on the standard Cockroft
and Gault formula.

- Patients of childbearing potential must have a negative serum pregnancy test within
14 days of treatment. Patients must agree to use a reliable method of birth control
during and for 3 months following the last dose of study drug.

- Patients must sign an informed consent document.

Exclusion Criteria:

- Previous exposure to temsirolimus or other mTOR inhibitors

- More than 2 prior cytotoxic regimens in the recurrent/metastatic disease setting

- History of any brain metastases

- Patients who require concomitant medications that are metabolized by hepatic CYP3A4,
due to potential drug-drug interaction with temsirolimus

- Patients with known active interstitial pneumonitis

- Active infection or serious underlying medical condition that would impair the
patient's ability to receive protocol treatment.

- Women who are pregnant or lactating

- Other active malignancy, other than indolent malignancies which the investigator
determines are unlikely to interfere with treatment and safety analysis

- Diagnosis of Nasopharyngeal cancer is excluded.

- Patients with multifocal peripheral sensory alterations or paresthesias (including
tingling) interfering with function, per patient report (example: activities of daily
living)

- Therapeutic anticoagulation with Coumadin (warfarin)

- Hypertriglyceridemia ≥ grade 2 (CTCAE version 3.0).

- Impaired lung function: O2 saturation 88% or less at rest on room air by Pulse
Oximetry. If O2 saturation is ≤ 88% at rest, further pulmonary function tests (PFTs)
should be ordered to confirm normal pulmonary function and eligibility.