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Phase II Study of Erlotinib for Patients With Malignant Peritoneal Mesothelioma (MPeM) Exhibiting EGFR Mutations

Phase 2
18 Years
Open (Enrolling)
Malignant Peritoneal Mesothelioma

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Trial Information

Phase II Study of Erlotinib for Patients With Malignant Peritoneal Mesothelioma (MPeM) Exhibiting EGFR Mutations


I. To determine the objective response rate (complete response [CR] + partial response [PR])
of erlotinib in malignant peritoneal mesothelioma (MPeM) patients who have epidermal growth
factor receptor (EGFR) mutations.


I. To determine the percentage of patients with MPeM who have EGFR mutations. II. To
characterize asbestos exposure history and other clinical parameters of patients with MPeM
who do or do not have EGFR mutations.

III. To determine the disease control rate (CR + PR + stable disease [SD]) of MPeM patients
who have EGFR mutations and are treated with erlotinib.

IV. To determine the progression-free survival (PFS) of MPeM patients who have EGFR
mutations and are treated with erlotinib.

V. To determine the median overall survival (OS) of MPeM patients who have EGFR mutations
and are treated with erlotinib.

VI. To evaluate toxicity in MPeM patients who have EGFR mutations and are treated with


I. To characterize the specific EGFR mutations observed in MPeM patients. II. To correlate
tumor markers (cancer antigen [CA] 125 and soluble mesothelin-related peptide [SMRP]) with
response rate, PFS, and OS in MPeM patients treated with erlotinib.

III. To correlate immunohistochemical staining of EGFR, phosphorylated (p)-EGFR, MET
(Metastasis), E-cadherin, vimentin, and CBL (Casitas B-lineage Lymphoma)with EGFR mutational
status and, if present, particular EGFR mutation noted.

IV. To correlate immunohistochemical staining of EGFR, p-EGFR, MET, E-cadherin, vimentin,
and CBL with response rate, PFS, and OS in MPeM patients treated with erlotinib.


Patients receive erlotinib hydrochloride orally (PO) once daily (QD). Courses repeat every
28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

- Histologically- or cytologically-confirmed malignant peritoneal mesothelioma;
epithelial, sarcomatoid, biphasic, or well-differentiated papillary subtypes are

- 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.

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Outcome Description:

The exact 95% confidence interval of the response rate will be reported.

Outcome Time Frame:

Up to 1 year

Safety Issue:


Principal Investigator

Hedy Kindler

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

June 2012

Completion Date:

March 2014

Related Keywords:

  • Malignant Peritoneal Mesothelioma
  • Mesothelioma



University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470