Phase II Two Arm Trial of the Proteasome Inhibitor, PS-341 (Velcade™) in Combination With Irinotecan or PS-341 Alone Followed by the Addition of Irinotecan at Time of Progression in Patients With Locally Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Inclusion Criteria

Inclusion criteria:

- Histologically confirmed squamous cell carcinoma of the head and neck

- Locally recurrent or metastatic disease

- Recurrent or metastatic disease must be confirmed by biopsy after prior
disease-free interval

- Not amenable to potentially curative local therapies OR patient has refused local
therapies

- Measurable disease

- At least 1 unidimensionally measurable lesion > 20 mm by conventional techniques
OR > 10 mm by spiral computed tomography (CT) scan

- Biopsy confirmation required for target lesions limited to an irradiated
location

- 18 and over

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

- Whole Blood Cell (WBC) ≥ 3,000/mm^3

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Bilirubin normal

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) test measures the
amount of this enzyme in the blood. ALT is found mainly (ALT) ≤ 2.5 times upper limit
of normal

- Creatinine normal OR Creatinine clearance ≥ 60 mL/min

- Negative pregnancy test

- Fertile patients must use effective contraception

Exclusion criteria:

- World Health Organization (WHO) type II or III nasopharyngeal cancer

- Primary salivary gland cancer

- Known brain metastases

- Pregnant or nursing

- Unstable angina pectoris

- Peripheral neuropathy ≥ grade 2 within the past 2 weeks

- Other invasive malignancy within the past 5 years

- History of allergic reaction to bortezomib

- History of allergic reaction attributed to compounds of similar chemical or

- Ongoing or active infection

- Psychiatric illness or social situation that would preclude study compliance

- Other uncontrolled illness

- Less than 4 weeks since prior chemotherapy for recurrent or metastatic disease

- More than 1 prior chemotherapy regimen for recurrent or metastatic squamous cell
carcinoma of the head and neck

- Prior irinotecan

- Prior bortezomib

- Concurrent radiotherapy

- Concurrent cyclosporine

- Concurrent antiepileptics

- Other concurrent investigational agents