Lenalidomide and Cetuximab in Treating Patients With Advanced Colorectal Cancer or Head and Neck Cancer

PRIMARY OBJECTIVES:

I. To determine the maximum-tolerated dose of lenalidomide when given in combination with
cetuximab in patients with advanced colorectal or squamous cell head and neck cancer.

SECONDARY OBJECTIVES:

I. To evaluate response in refractory V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog
(KRAS) wild-type colorectal and head/neck cancers as monitored by measurable disease by
Response Evaluation Criteria In Solid Tumors (RECIST) criteria.

II. To measure antibody-dependent cytotoxic activity (ADCC) in patients receiving
lenalidomide plus cetuximab.

III. To measure natural killer cell cytokine production in patients receiving lenalidomide
plus cetuximab.

IV. To describe fragment c gamma receptor polymorphisms. (Exploratory) V. To describe
baseline immune cell function. (Exploratory)

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

Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21 and cetuximab
intravenously (IV) over 1-2 hours on days 1 and 15. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 6 weeks.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed malignancy that is
metastatic or unresectable and for which standard curative or palliative measures do
not exist or are no longer effective; eligible malignancies include: colorectal cancer
KRAS wild-type and squamous cell head and neck cancer

- No curative intent therapy available; there is no limit on prior number of therapies;
prior epidermal growth factor receptor (EGFR)-directed therapy (tyrosine kinase
inhibitors and monoclonal antibodies - including cetuximab, panitumumab, or
investigational EGFR directed monoclonal antibodies) will be allowed in the phase I
dose escalation; patients who have received monoclonal antibody therapy must be off
all monoclonal antibodies four weeks (28 days) prior to study treatment; no
chemotherapy within 28 days of trial medication

- There will be an expansion cohort for colorectal cancer patients only; for the
expansion cohort, there is no limit on prior chemotherapy; the colorectal expansion
cohort will include patients with cetuximab or panitumumab-resistant or refractory
disease (progression during cetuximab/panitumumab therapy or within 3 months of
cetuximab/panitumumab therapy

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky > 60%)

- Life expectancy of greater than 3 months

- Leukocytes > 3,000/mcL

- Absolute neutrophil count > 1,500/mcL

- Platelets > 100,000/mcL

- Total bilirubin within normal institutional limits

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
< 2.5 x institutional upper limit of normal

- Creatinine clearance > 60 mL/min/1.73 m^2 as calculated using modified Cockcroft-Gault
formula

- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24
hours prior to starting cycle 1 of lenalidomide; further, they must either commit to
continued abstinence from heterosexual intercourse or begin TWO acceptable methods of
birth control: one highly effective method and one additional effective method AT THE
SAME TIME, at least 28 days before starting lenalidomide; FCBP must also agree to
ongoing pregnancy testing; men must agree to use a latex condom during sexual contact
with a FCBP, even if they have had a successful vasectomy; a FCBP is a sexually mature
woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has
not been naturally postmenopausal for at least 24 consecutive months (i.e., has had
menses at any time in the preceding 24 consecutive months); all patients must be
counseled by a trained counselor every 28 days about pregnancy precautions and risks
of fetal exposure

- Men must agree to use a latex condom during sexual contact with a FCBP even if they
have had a successful vasectomy

- All patients must be counseled at a minimum of every 28 days about pregnancy
precautions and risks of fetal exposure

- Able to take aspirin (81 or 325 mg) daily for prophylactic anticoagulation (patients
intolerant to aspirin may use warfarin or low molecular weight heparin)

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events (>= grade 3) due to agents administered more than 4
weeks earlier

- Patients may not be receiving any other investigational agents

- Uncontrolled brain metastases; patients who have received definitive therapy,
including radiation, and are not requiring ongoing medical therapy (i.e. steroids) for
brain metastases will be allowed

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to lenalidomide or cetuximab or other agents used in study

- Patients with a recent history of deep vein thrombosis (DVT)/pulmonary embolism (PE)
requiring therapy (within 3 months)

- Patients with history of toxicity >= grade 3 with prior EGFR directed therapy

- Patient with confirmed history of interstitial lung disease

- Uncontrolled concurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with either agent

- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy are ineligible