Non-small Cell Lung Cancer
Conditions
Keywords
cetuximab, tyrosine kinase inhibitor
Brief summary
The purpose of this research study is to find out how well cetuximab works in treating NSCLC in patients who have been previously treated with a class of drug called tyrosine kinase inhibitor (TKI). Cetuximab is a protein that is designed to block a substance in cancer cells called epidermal growth factor receptor or EGFR. EGFR helps cancer cells grow.
Detailed description
* Participants on this study will receive cetuximab by infusion intravenously once per week and may continue to receive weekly cetuximab infusions until their disease progresses or they experience unacceptable side effects. * The following will be performed every 4 weeks while they are receiving study treatments: Physical examination; performance status; and blood work. A CT scan of the chest and upper abdomen will be performed every 8 weeks.
Interventions
DRUGCetuximab
Given intravenously once per week.
Sponsors
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Unity Health Toronto
Bristol-Myers Squibb
Lecia V. Sequist
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically confirmed stage IIIB or IV recurrent or progressive NSCLC * Patients must have progressed while receiving treatment with a tyrosine kinase inhibitor targeting the EGFR pathway * Measurable disease, as defined by RECIST criteria * Patients must have a suitable frozen or paraffin-embedded tissue sample available for EGFR mutational analysis. Prior EGFR mutational analyses are allowable * Patients with asymptomatic brain metastasis are eligible; however, they must have completed radiotherapy/radiosurgery at least 3 weeks prior to enrollment and be clinically stable * ECOG Performance Status 0-2 * 18 years of age or older * Negative pregnancy test within 7 days of treatment or be categorized as not of child-bearing potential * Bone marrow function, renal function, hepatic function as outlined in protocol
Exclusion criteria
* Women who are pregnant of breastfeeding * Active concurrent malignancy * Major thoracic or abdominal surgery within 30 days prior to the first infusion of cetuximab * Significant history of uncontrolled cardiac disease * Uncontrolled seizure disorder, or active neurological disease * Prior severe infusion reactions to a monoclonal antibody * Prior chemotherapy regimen within 21 days prior to study entry * Any EGFR tyrosine kinase inhibitor within 14 days of study entry * Radiation therapy within 14 days prior to the first infusion of cetuximab * Acute hepatitis or known HIV * Active or uncontrolled infection * Any concurrent chemotherapy or any other investigational agent(s)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response Rate by CT Scan Using RECIST Criteria | 8 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free Survival | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months |
Countries
United States
Participant flow
Recruitment details
We recruited patients to this multicenter, single-arm, phase II clinical trial with ECOG PS 0 to 2 and advanced NSCLC who were previously treated with erlotinib or gefitinib. Patients with asymptomatic, stable CNS metastases were eligible. 18 eligible patients were enrolled in the first stage of the trial between October 2006 and March 2009.
Pre-assignment details
All patients were required to have an available tissue sample for EGFR mutation testing, which was performed centrally at a CLIA-certified laboratory.
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab Patients received intravenous cetuximab, 400 mg/m2, followed by weekly infusions of 250 mg/m2. Four weekly treatments constituted one cycle. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Cetuximab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 18 |
| serious Total, serious adverse events | 4 / 18 |
Outcome results
Primary
Response Rate by CT Scan Using RECIST Criteria
Time frame: 8 weeks
Population: The trial used a Simon two-stage design, which enrolled 18 pts in the first stage and was to proceed to enroll an additional 28 evaluable patients if 1 or more response was observed in the first group. This design provided a 57% chance of early termination if the true response rate was \<3%. PFSand OS were calculated using the Kaplan-Meier method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab | Response Rate by CT Scan Using RECIST Criteria | 0 participants |
Secondary
Progression-free Survival
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab | Progression-free Survival | 1.8 months |