Erlotinib Hydrochloride in Treating Patients With Malignant Peritoneal Mesothelioma

Inclusion Criteria:

* Histologically- or cytologically-confirmed malignant peritoneal mesothelioma; epithelial, sarcomatoid, biphasic, or well-differentiated papillary subtypes are allowed.
* A tumor block or 10 unstained slides must be available for determining EGFR mutational status; only those patients who have a mutation of the EGFR tyrosine kinase domain will be able to enroll in this study.
* Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan.
* No prior use of EGFR tyrosine kinase inhibitors or monoclonal antibodies; all other prior treatments are allowed if \>= 4 weeks since treatment completed, including chemotherapy (systemic or intraperitoneal), radiation therapy, and/or surgery; there is no limit on the number of previous treatments allowed.
* Life expectancy of greater than 3 months.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
* Leukocytes \>= 2,000/mcL.
* Absolute neutrophil count \>= 1,500/mcL.
* Platelets \>= 100,000/mcL.
* Total bilirubin =\< 1.5 X institutional upper limit of normal (ULN).
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 X institutional ULN.
* Creatinine =\< 2 X institutional ULN OR creatinine clearance \>= 30 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal.
* The effects of erlotinib on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* Ability to understand and the willingness to sign a written informed screening and treatment consent.

Exclusion Criteria:

* Chemotherapy, radiotherapy, or surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
* Patients may not be receiving any other investigational agents.
* Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop. progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib.
* EGFR-mutation negative tumor tissue as determined by sequencing; if an individual tissue test result is inconclusive (unable to be determined), it will be considered negative for study eligibility purposes.
* History of previous malignancy excluding non-melanoma skin lesions and in-situ cervical cancer; patients with other malignancies are eligible if they have been disease free for \>= 3 years.
* Uncontrolled intercurrent 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 because it is unknown if erlotinib poses a potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with erlotinib, breastfeeding should be discontinued if the mother is treated with erlotinib.
* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with erlotinib; in addition, these patients are at increased risk of lethal infections; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
* Inability to tolerate or absorb an oral medication due to any cause, including but not limited to malabsorption syndromes.