Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
African Americans
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.
Interventions
DRUGerlotinib
Arm A: 150 mg/day cycles 1 - 3. Arm B: Cycle 1 - 175 or 200 mg/day depending on body weight; Cycle 2 - if rash developed, then 150 mg/day; if no rash, then 175 mg/day; Cycle 3 - if rash developed, then 175 mg/day; if no rash, then 200 mg/day.
Sponsors
Genentech, Inc.
Ohio State University Comprehensive Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate at 12 Weeks | 12 weeks | no progression of disease at 12 weeks from starting treatment |
| Time to Progression | Every 12 weeks | — |
| 1-year Survival Rate | 12 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: 150 mg/Day 150 mg/day
erlotinib: Arm A: 150 mg/day Arm B: Cycle 1 - 175 or 200 mg/day depending on body weight; Cycle 2 - if rash developed, then 150 mg/day; if no rash, then 175 mg/day; Cycle 3 - if rash developed, then 175 mg/day; if no rash, then 200 mg/day. | 28 |
| Arm B: Cycle 1 - 150-200 mg/Day Depending on Body Weight Cycle 1 dose modified according to patient's weight; Cycles 2 and up, dose titrated to generate skin rash.
Arm B: Cycle 1 - 175 or 200 mg/day depending on body weight; Cycle 2 - if rash developed, then 150 mg/day; if no rash, then 175 mg/day; Cycle 3 - if rash developed, then 175 mg/day; if no rash, then 200 mg/day. | 27 |
| Total | 55 |
Baseline characteristics
| Characteristic | Arm A: 150 mg/Day | Arm B: Cycle 1 - 150-200 mg/Day Depending on Body Weight | Total |
|---|---|---|---|
| Age, Continuous | 63 years | 59 years | 62 years |
| Sex: Female, Male Female | 11 Participants | 13 Participants | 24 Participants |
| Sex: Female, Male Male | 17 Participants | 14 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 28 | 19 / 27 |
| serious Total, serious adverse events | 1 / 28 | 0 / 27 |
Outcome results
Primary
1-year Survival Rate
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib: Arm A: 150 mg/Day Cycles 1 - 3. | 1-year Survival Rate | 30 percentage of patients |
| Arm B: Cycle 1 - 175 or 200 mg/Day Depending on Body Weight; C | 1-year Survival Rate | 26 percentage of patients |
Primary
Disease Control Rate at 12 Weeks
no progression of disease at 12 weeks from starting treatment
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erlotinib: Arm A: 150 mg/Day Cycles 1 - 3. | Disease Control Rate at 12 Weeks | 6 participants |
| Arm B: Cycle 1 - 175 or 200 mg/Day Depending on Body Weight; C | Disease Control Rate at 12 Weeks | 6 participants |
Primary
Time to Progression
Time frame: Every 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib: Arm A: 150 mg/Day Cycles 1 - 3. | Time to Progression | 2.8 months |
| Arm B: Cycle 1 - 175 or 200 mg/Day Depending on Body Weight; C | Time to Progression | 2.4 months |