This phase I trial studies the side effects and the best dose of lenalidomide when given
together with cetuximab in treating patients with colorectal cancer or head and neck cancer
that has spread to other places in the body and usually cannot be cured or controlled with
treatment. Biological therapies, such as lenalidomide, use substances made from living
organisms that may stimulate the immune system in different ways and stop tumor cells from
growing. Monoclonal antibodies, such as cetuximab, may block tumor growth in different ways
by targeting certain cells. Giving lenalidomide together with cetuximab may be a better
treatment for colorectal cancer or head and neck cancer.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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