Trial Outcomes & Findings for Phase II Trial to Correlate Radiographic Response Induced By Gefitinib With Mutations in the Protein-Tyrosine Kinase Domain of the EGF Receptor Gene (NCT NCT00588445)

Results Overview

Radiographic response is defined as a minor response ( \> 25% decrease in the sum of the products of measured lesions)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

65 participants

Primary outcome timeframe

21 days

Results posted on

2016-01-22

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	65
Overall Study COMPLETED	50
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Protocol Violation	1
Overall Study Withdrawal by Subject	3
Overall Study Disease Progression	1
Overall Study Not Treated	10

Baseline Characteristics

Phase II Trial to Correlate Radiographic Response Induced By Gefitinib With Mutations in the Protein-Tyrosine Kinase Domain of the EGF Receptor Gene

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment n=65 Participants 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.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	33 Participants n=99 Participants
Age, Categorical >=65 years	32 Participants n=99 Participants
Sex: Female, Male Female	51 Participants n=99 Participants
Sex: Female, Male Male	14 Participants n=99 Participants
Region of Enrollment United States	65 participants n=99 Participants

PRIMARY outcome

Timeframe: 21 days

Radiographic response is defined as a minor response ( \> 25% decrease in the sum of the products of measured lesions)

Outcome measures

Outcome measures
Measure	Treatment n=50 Participants 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.	EGFR Mutation Negative Tumor specimens analyzed for EGFR mutation
The Radiographic Response to Gefitinib	21 participants	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment n=17 Participants 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.	EGFR Mutation Negative n=4 Participants Tumor specimens analyzed for EGFR mutation
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	76 percentage of participants
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	92 percentage of participants

Adverse Events

Treatment

Serious events: 7 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment n=65 participants at risk 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.
Cardiac disorders Atrial fibrillation	1.5% 1/65 • Number of events 1
Psychiatric disorders Confusion	1.5% 1/65 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnea	3.1% 2/65 • Number of events 2
Respiratory, thoracic and mediastinal disorders Pneumothorax	3.1% 2/65 • Number of events 2
Eye disorders Retinopathy	1.5% 1/65 • Number of events 1
Vascular disorders Thrombosis/thrombus/embolism	1.5% 1/65 • Number of events 1
Vascular disorders Vascular disorder	1.5% 1/65 • Number of events 1

Other adverse events

Other adverse events
Measure	Treatment n=65 participants at risk 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.
Gastrointestinal disorders Diarrhea	9.2% 6/65 • Number of events 6
General disorders Fatigue	9.2% 6/65 • Number of events 6
Skin and subcutaneous tissue disorders Rash: acne/acneiform	7.7% 5/65 • Number of events 6

Additional Information

Dr. Charles Rudin

Memorial Sloan Kettering Cancer Center

Phone: 646-888-4527

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place