Clinical trial NCT00230126: OSI-774 in African American Patients With Advanced and Previously Treated Non-Small Cell Lung Cancer
Official title: A Phase II Randomized Study of OSI-774 in African American Patients With Advanced and Previously Treated Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: African Americans
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2005-09-30
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study determines tumor response rate, time to tumor progression and survival rate at 1 year produced by OSI-774 in previously treated African American patients with nonsmall cell lung cancer.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Must have histologically or cytologically confirmed stage IIIB or IV NSCLC treated with 1-2 platinum- or taxane-containing regimens
* Measurable disease
* May have had prior surgery \& external beam radiation
* African American
* 18 years or older

Exclusion Criteria:

* Known brain mets
* Prior treatment with EGFR targeting therapies
* Pregnant/lactating women

Primary outcomes:
measure: Disease Control Rate at 12 Weeks
timeFrame: 12 weeks
measure: Time to Progression
timeFrame: Every 12 weeks
measure: 1-year Survival Rate
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
affiliation: Ohio State University
name: Miguel Villalona, M.D.
role: PRINCIPAL_INVESTIGATOR
References: