A Phase II Randomized Study of OSI-774 in African American Patients With Advanced and Previously Treated Non-Small Cell Lung Cancer (NSCLC)
Rationale: Researchers are seeking to identify treatment regimens with low toxicity for
non-small cell lung cancer (NSCLC), especially for African Americans with this disease who
seem to have a larger burden of comorbidities and decreased performance status. The current
study uses a drug called OSI-774 in previously treated African American patients with NSCLC.
OSI-774 is a targeted agent designed as an EGFR tyrosine kinase inhibitor. Previous research
indicates that tumor cells overexpress EGFR receptors, and this drug works by blocking these
receptors on tumor cells that that help them grow.
OSI-774 is FDA approved for the treatment of patients with non-small cell lung cancer that
had been previously treated with chemotherapy. Unfortunately, very little data exist in the
pharmacokinetics and metabolism of EGFR blockers in African Americans and in the assessment
of how efficacious these agents are in this patient group. Yet, research suggests that EGFR
blockage may have a greater impact on this patient population. Since the development of skin
rash following therapy with EGFR blockers may be a surrogate of obtaining sufficient
concentrations at the tissue level and potential efficacy, the current study is a randomized
phase II trial designed to compare normal dose levels of OSI-774 with dose levels determined
by body weight and with subsequent amounts adjusted further into the study to generate a
skin rash. Through the current study, researchers are testing their theory that this dosing
method will increase the number of patients with effective tissue concentrations and result
in an increase in patient responses.
Purpose: The primary objective of this study is to determine the objective tumor response
rate, the time to tumor progression, and the survival rate at one year produced by OSI-774
in previously treated African American patients with advanced NSCLC. A second objective is
to evaluate if a regimen of single agent OSI-774, with dosing initially influenced by body
weight and with subsequent titration to achieve skin rash is a suitable regimen for future
studies of this agent. A third objective is to measure if changes in EGFR from tumor and
blood cells correlate with the development of rash and clinical benefit. The
pharmacokinetics of OSI-774 will also be characterized through study participants.
Treatment: Patients in this study will be given OSI-774. A computer will randomly assign
patients into one of two treatment groups. Group one will be given a standard dose of
OSI-774. The dose of OSI-774 will not be increased in group one. However, patients in group
one will have the dose level decreased due to unacceptable side effects. Group two will
receive OSI-774 at a dose modified to their body weight at study entry and subsequently
adjusted further into the study to generate a skin rash. For all study participants, OSI-774
will be administered daily in oral pills. Several tests and exams will be given throughout
the study to closely monitor patients. Treatments will be discontinued due to disease growth
or unacceptable side effects.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
tumor response rate
Every 12 weeks
Miguel Villalona, M.D.
Ohio State University
United States: Food and Drug Administration
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