Bortezomib and Cetuximab in Treating Patients With Advanced Solid Tumors

OBJECTIVES:

Primary

- To determine the maximum tolerated dose of bortezomib when given together with cetuximab
in patients with advanced solid tumors expressing epidermal growth factor receptor
(EGFR).

Secondary

- To obtain preliminary information about the anti-tumor activity of bortezomib and
cetuximab.

OUTLINE: This is a dose-escalation study of bortezomib.

Patients receive bortezomib intravenously (IV) on days 1 and 8 and cetuximab IV over 60-90
minutes on days 1, 8, and 15. Treatment repeats every 21 days for up to 6 courses in the
absence of disease progression or unacceptable toxicity.

After the maximum tolerated dose (MTD) is determined, an additional 10 patients are treated
at the MTD.

After completion of study treatment, patients are followed periodically for up to 1 year.

Inclusion Criteria:

- Diagnosis of solid tumor that overexpresses epidermal growth factor receptor (EGFR)
including, but not limited to, the following:

- Breast cancer

- Lung cancer

- Colon cancer

- Pancreatic cancer

- Head and neck cancer

- Kidney cancer

- Sarcoma

- Advanced disease

- Must have failed or become intolerant to prior standard therapy and is no longer
likely to respond to such therapy

- Measurable or nonmeasurable disease

- ECOG performance status 0-1

- ANC ≥ 1,500/mm³

- Platelet count > 100,000/mm³

- Hemoglobin > 9 g/dL

- Bilirubin < 1.5 times upper limit of normal (ULN)

- Alkaline phosphatase < 3.0 times ULN (5.0 times ULN if liver has tumor involvement)

- Aspartate aminotransferase (AST) and alanine aminotransferase (*ALT) < 3.0 times upper
limit of normal (ULN) (5.0 times ULN if liver has tumor involvement)

- Creatinine clearance > 30 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment

- Recovered from all prior therapy

- Prior systemic chemotherapy, immunotherapy, or biological therapy allowed

- At least 14 days since prior radiotherapy or systemic therapy

- At least 30 days since prior investigational agents

- At least 14 days since other prior investigational drugs (for reasons other than the
treatment of cancer)

Exclusion Criteria:

- Untreated or symptomatic central nervous system (CNS) metastases

- Concurrent serious systemic disorders (e.g., active infection) that, in the opinion of
the investigator, would compromise the safety of the patient or compromise the
patient's ability to complete the study

- Uncontrolled diabetes

- Myocardial infarction within the past 6 months

- New York Heart Association (NYHA) class III or IV heart failure

- Uncontrolled angina

- Severe uncontrolled ventricular arrhythmias

- Evidence of acute ischemia or active conduction system abnormalities by ECG

- Peripheral neuropathy Common Terminology Criteria for Adverse Events (CTCAE) grade > 2

- Known hypersensitivity to bortezomib, boron, or mannitol

- Serious medical or psychiatric illness likely to interfere with study participation

- Prior bortezomib and/or cetuximab

- Concurrent filgrastim (G-CSF) or other hematologic support during course 1 of study
treatment