Bronchioloalveolar Cancer, Lung Cancer, Non-small Cell Lung Cancer
Conditions
Keywords
Lung Cancer, Non-small cell lung cancer, Gefitnib, Cancer, NSCLC, bronchioloalveolar cancer, smoker
Brief summary
The purpose of this research study is to: * see if gefitinib pills can shrink Stage 1 or 2 non-small cell lung cancers before surgery * see if your non-small cell lung cancer has a mutation in a certain part of the EGFR gene * see if patients whose tumor does shrink with gefitinib treatment are more likely to have a mutation in a certain part of the EGFR gene * see if the pattern of protein expression in the blood is related to the tumor's sensitivity or resistance to gefitinib treatment. * see if expression of certain genes in the tumor are related to the tumor's sensitivity or resistance to gefitinib treatment.
Detailed description
This is a phase II, single institution trial to correlate gefitinib response and mutations in the protein-tyrosine kinase domain of the EGF receptor gene. The study will be conducted in patients with Stage I and II NSCLC who have been determined to be operable and resectable. Patients must have 1 or more of the following features: never smoker or smoking history of \< 15 pack years and/or features of bronchioloalveolar lung cancer. 50 patients will be enrolled on this study. Treatment will be with gefitinib for at least 21 days before surgery (depending on the timing of the surgery). Patients will discontinue gefitinib 2 days before their operation. For patients that demonstrate a radiographic response to gefitinib preoperatively and /or patients with mutations in the protein-tyrosine kinase domain of the EGF receptor gene (identified from the surgical sample), gefitinib will continue for 2 years post-surgery. Patients who do not have evidence of radiographic response or mutations in the protein-tyrosine kinase domain of the EGF receptor gene will be removed from the study.
Interventions
DRUGGefitinib
Patients will receive gefitinib 250 mg po daily for at least 21 days preoperatively (depending on the timing of the surgery). Treatment with gefitinib will be stopped 2 days before the date of surgery. Patients who have had at least a minor response to gefitinib therapy preoperatively (\> 25% reduction in tumor measured bidimensionally) and / or have mutations in the protein-tyrosine kinase domain of the EGF receptor gene identified will continue on the study and will resume gefitinib treatment after at least 7 days from surgery providing adequate wound healing has occurred. Patients who are determined to be candidates for adjuvant chemotherapy and/or radiation therapy by their treating physician may receive treatment with adjuvant chemotherapy and/or radiation therapy. The post-operative gefitinib will be started after completion of the chemotherapy and/or radiation therapy.
Sponsors
Memorial Sloan Kettering Cancer Center
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
* Pathologic confirmation of malignancy at Memorial Sloan-Kettering * Patients must have previously untreated stage I or II NSCLC (T11-2N0M0, T1-2N1M0, T3N0M0) and 1 of the following features: never smoker or \< 15 pack year smoking history and/or bronchioloalveolar cancer (either pure BAC, BAC with focal invasion or adenocarcinoma with BAC features) * Patients must have been determined to be operable and resectable by the treating thoracic surgeon. * Age \>18 years. * Measurable indicator lesions * Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
* Pregnant or lactating women or women of childbearing potential not using effective contraception. Men participating in the trial must also use effective contraception when sexually active. * Patients may not be receiving any other investigational agents. * Any history of or evidence of interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Radiographic Response to Gefitinib | 21 days | Radiographic response is defined as a minor response ( \> 25% decrease in the sum of the products of measured lesions) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Microarray Analysis to Identify Gene(s) or Gene Clusters That Exhibit Changes in Gene Expression; Time to Relapse and Overall Survival Data | 2 years | Each patient provides two binary variables: presence/absence of mutation and responder/non responder. The association between the two will be tested using the Fisher's exact test for the resulting 2x2 table.Changes in expression levels within a patient will be assessed using a paired t-test. Similarly differences in expression levels between responders and non-responders will be assessed using a two-sample t-test. Appropriate adjustment will be made for the multiple comparisons problem that arises because there are over 21,000 probe sets on the U133A array. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Gefitinib: Patients will receive gefitinib 250 mg po daily for at least 21 days preoperatively (depending on the timing of the surgery). Treatment with gefitinib will be stopped 2 days before the date of surgery.
Patients who have had at least a minor response to gefitinib therapy preoperatively (\> 25% reduction in tumor measured bidimensionally) and / or have mutations in the protein-tyrosine kinase domain of the EGF receptor gene identified will continue on the study and will resume gefitinib treatment after at least 7 days from surgery providing adequate wound healing has occurred.
Patients who are determined to be candidates for adjuvant chemotherapy and/or radiation therapy by their treating physician may receive treatment with adjuvant chemotherapy and/or radiation therapy. The post-operative gefitinib will be started after completion of the chemotherapy and/or radiation therapy. | 65 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease Progression | 1 |
| Overall Study | Not Treated | 10 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 32 Participants |
| Age, Categorical Between 18 and 65 years | 33 Participants |
| Region of Enrollment United States | 65 participants |
| Sex: Female, Male Female | 51 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 65 |
| serious Total, serious adverse events | 7 / 65 |
Outcome results
Primary
The Radiographic Response to Gefitinib
Radiographic response is defined as a minor response ( \> 25% decrease in the sum of the products of measured lesions)
Time frame: 21 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | The Radiographic Response to Gefitinib | 21 participants |
Secondary
Microarray Analysis to Identify Gene(s) or Gene Clusters That Exhibit Changes in Gene Expression; Time to Relapse and Overall Survival Data
Each patient provides two binary variables: presence/absence of mutation and responder/non responder. The association between the two will be tested using the Fisher's exact test for the resulting 2x2 table.Changes in expression levels within a patient will be assessed using a paired t-test. Similarly differences in expression levels between responders and non-responders will be assessed using a two-sample t-test. Appropriate adjustment will be made for the multiple comparisons problem that arises because there are over 21,000 probe sets on the U133A array.
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment | Microarray Analysis to Identify Gene(s) or Gene Clusters That Exhibit Changes in Gene Expression; Time to Relapse and Overall Survival Data | Disease Free Survival | 85 percentage of participants |
| Treatment | Microarray Analysis to Identify Gene(s) or Gene Clusters That Exhibit Changes in Gene Expression; Time to Relapse and Overall Survival Data | Overall Survival | 98 percentage of participants |
| EGFR Mutation Negative | Microarray Analysis to Identify Gene(s) or Gene Clusters That Exhibit Changes in Gene Expression; Time to Relapse and Overall Survival Data | Disease Free Survival | 76 percentage of participants |
| EGFR Mutation Negative | Microarray Analysis to Identify Gene(s) or Gene Clusters That Exhibit Changes in Gene Expression; Time to Relapse and Overall Survival Data | Overall Survival | 92 percentage of participants |