Temsirolimus (Torisel®) and Erlotinib (Tarceva®) in Platinum-Refractory/Ineligible, Advanced, Squamous Cell Carcinoma

This is a phase II, multicenter, single arm, open-label study. Thirty-seven patients with
advanced, platinum-refractory or platinum-ineligible squamous cell carcinoma of the head and
neck will be sequentially enrolled to a single treatment arm. Patients will be treated with
continuous, 28-day cycles of 150 mg of erlotinib by mouth daily and 15 mg of temsirolimus
intervenously weekly. In the absence of grade 3 or higher toxicity in the first cycle, a
single, intra-patient dose increase to 20 mg temsirolimus will be permitted.

Inclusion Criteria:

1. Histologically or cytologically confirmed squamous cell carcinoma of the head and
neck, from any primary site. Nasopharyngeal carcinoma, World Health Organization
(WHO) Grade I, will be included.

2. Advanced disease, fulfilling 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

3. Platinum-refractory or platinum-ineligible, fulfilling one of the criteria defined
below:

- disease progression during or after 4-6 cycles of platinum-containing therapy in
the advanced setting

- disease progression within 6 months of curative-intent treatment, which included
platinum-based chemotherapy

- ineligible for platinum-containing therapy, in the opinion of the medical
oncologist, due to medical comorbidities or unacceptable risk for toxicity

- patient refuses platinum-containing therapy

4. Measurable disease based on response evaluation criteria in solid tumors (RECIST)

- disease in previously irradiated sites is considered measurable if there has been
unequivocal progression of the lesion after radiotherapy, or the lesion contains
residual carcinoma by biopsy more than 6 weeks after completion of radiotherapy

5. Easter Cooperative Oncology Group (ECOG) performance status 0-2 at time of informed
consent

6. Adequate hematologic reserve and organ function

- Absolute neutrophil count > 1200/µl

- Platelet count > 100,000/µl

- Renal function: Serum Creatinine ≤ 1.5x upper limit of normal (ULN)

- Liver function: Total bilirubin ≤ 1.5x ULN, Aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) ≤ 2.5x ULN

7. Able to provide written, voluntary consent

8. Patients with reproductive potential must use an effective contraceptive method.

9. Male or female, age ≥ 18 years

10. Life expectancy ≥ 12 weeks

Exclusion Criteria:

1. Nasopharyngeal primary site, if WHO grade II or III

2. Prior treatment blocking the epidermal growth factor receptor (EGFR), in the advanced
disease setting

3. Prior treatment blocking EGFR in the curative-intent setting, if delivered in the
previous 6 months

4. Prior treatment with a drug blocking the mammalian target of rapamycin (mTOR)

5. Sensitivity to temsirolimus or erlotinib

6. Uncontrolled metastatic disease of the central nervous system

7. Radiotherapy within the 2 weeks before Cycle 1' Day 1

8. Surgery within the 2 weeks before Cycle 1' Day 1

9. Pregnant or lactating females

10. Myocardial infarction or ischemia within the 6 months preceding study treatment

11. Any co morbid condition that' in the view of the attending physician' renders the
patient at high risk from treatment complications

12. No other concurrent, investigational anti-neoplastic agent will be permitted

13. History of prior malignancy within the prior five years, with the exception of
non-melanoma carcinomas of the skin, and carcinoma in situ of the cervix