Phase II Trial of Doxorubicin and Bortezomib in Patients With Incurable Head and Neck Adenoid Cystic Carcinoma

Inclusion Criteria:

- Patients must have locally advanced, recurrent, or metastatic adenoid cystic
carcinoma of the head and neck which is considered incurable by known therapies, as
judged by the investigator.

- Patients should have cytologically or histologically confirmed adenoid cystic
carcinoma of the head and neck.

- Patients must have unidimensionally measurable disease (RECIST criteria). If the only
site of measurable disease is a previously irradiated area, the patient must have
documented progression of disease in this area.

- All available prior computed tomography (CT) or magnetic resonance imaging (MRI)
scans should be reviewed and noted, and measurements showing progression of disease
should be documented whenever possible. However, documentation of disease progression
is not mandatory for enrollment.

- Patients must have multigated acquisition scan (MUGA) scan showing left ventricular
ejection function (LVEF) at or above the institutional lower limits of normal.

- Patients must have ECOG performance status 0-2.

- Patients should have recovered from prior surgery or radiation therapy. A minimum
time period of 3 weeks should elapse between the completion of extensive radiation
therapy for recurrent/metastatic disease and enrollment in the study.

- Patients must have normal organ and marrow function (as defined below) measured
within one week prior to registration:

- Absolute neutrophil count >1,500/mm3.

- Platelets greater than or equal to 100,000/mm3.

- Total bilirubin within normal institutional limits.

- Transaminases (AST and ALT) <3 X ULN.

- Creatinine within normal institutional limits or creatinine clearance (CrCl) greater
than or equal to 60 mL/min/1.73 m2 for patients with creatinine levels above
institutional normal. CrCl will be calculated using the Cockcroft-Gault formula:

- Calculated Creatinine Clearance = (140-age) X actual body wt.(kg) 72 X serum
creatinine. Multiply this number by 0.85 if the patient is female.

- Myocardial infarction within 6 months prior to enrollment, uncontrolled angina,
severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of
acute ischemia or active conduction system abnormalities. Prior to study entry, any
ECG abnormality at screening has to be documented by the investigator as not
medically relevant. Patients must not have history of congestive heart failure of any
grade according to Heart Association (NYHA) (see Appendix 2).

- Age > 18 years and capacity to give informed consent.

- All patients must have given signed, informed consent prior to registration to the
study.

Exclusion Criteria:

- No prior chemotherapy for recurrent / metastatic adenoid cystic carcinoma. Up to 1
prior biologic/targeted therapy regimen is allowed. Also, chemotherapy as part of
initial potentially curative therapy (i.e. concurrent chemoradiotherapy) is allowed,
if it was completed >6 months earlier.

- Patients must not have any prior anthracyclines (doxorubicin, epirubicin,
daunorubicin, idarubicin) or mitoxantrone, or bortezomib.

- No history of prior malignancy, with the exception of curatively treated squamous
cell or basal carcinoma of the skin or in situ cervical cancer, unless there is a
3-year disease-free interval.

- Patients must not have history of allergic reactions attributed to compounds of
similar chemical or biologic composition to bortezomib, boron or mannitol.

- Patients must not have any pre-existing neuropathy of grade > 1.

- Patients must not have uncontrolled intercurrent illness including, but not limited
to, ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, or
psychiatric illness/social situations that would limit compliance with study
requirements.

- Female patients who are pregnant or breast feeding or patients of reproductive
potential not using an effective method of birth control will be excluded. Women of
childbearing potential must have a negative serum pregnancy test within 2 weeks of
the first administration of chemo. Also, male patients whose sexual partners are
women of child bearing potential not using effective birth control will be excluded.

- Patients with known positivity for human immunodeficiency virus (HIV) will be
excluded due to possible pharmacokinetic interactions with bortezomib. Appropriate
studies will be undertaken in HIV-positive patients who are receiving or not
receiving combination anti-retroviral therapy when indicated.

- Patient must not have received other investigational drugs within 14 days before
enrollment.