Trial Outcomes & Findings for Stereotactic Radiosurgery or Other Local Ablation Then Erlotinib in Epidermal Growth Factor Receptor (EGFR) (NCT NCT01573702)
NCT ID: NCT01573702
Last Updated: 2021-01-12
Results Overview
Progression free survival (PFS) after locally ablative therapy and erlotinib in EGFR-mutant NSCLC patients who progressed on prior EGFR-tyrosine kinase inhibitor (TKI) therapy reported as percentage of participants who are alive and without progressive disease at 3 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or the appearance of new lesions.
COMPLETED
PHASE2
32 participants
3 months after Initiation of Stereostatic Radiotherapy
2021-01-12
Participant Flow
32 participants were accrued from six institutions between 12/2012 and 6/2016
Of the 32 participants who consented to the study, 5 were determined to be not eligible and 2 withdrew consent prior to starting study treatment
Participant milestones
| Measure |
Stereotactic Radiosurgery Followed by Erlotinib
Stereotactic Radiosurgery or Other Local Ablation Followed by Erlotinib
Stereotactic Radiosurgery: 21 Gy daily for 5 days
Erlotinib: 150mg once daily
|
|---|---|
|
Overall Study
STARTED
|
25
|
|
Overall Study
COMPLETED
|
25
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Stereotactic Radiosurgery or Other Local Ablation Then Erlotinib in Epidermal Growth Factor Receptor (EGFR)
Baseline characteristics by cohort
| Measure |
Stereotactic Radiosurgery Followed by Erlotinib
n=25 Participants
Stereotactic Radiosurgery or Other Local Ablation Followed by Erlotinib
Stereotactic Radiosurgery: 21 Gy daily for 5 days
Erlotinib: 150mg once daily
|
|---|---|
|
Age, Continuous
|
64 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
25 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
25 participants
n=5 Participants
|
|
Smoking status
Never smoker
|
16 Participants
n=5 Participants
|
|
Smoking status
Former smoker
|
7 Participants
n=5 Participants
|
|
Smoking status
Unknown
|
2 Participants
n=5 Participants
|
|
Performance status
0, Fully active
|
16 Participants
n=5 Participants
|
|
Performance status
1, Restricted in strenuous activity but ambulatory
|
9 Participants
n=5 Participants
|
|
Mutation type
Exon 19
|
14 Participants
n=5 Participants
|
|
Mutation type
Exon 21
|
7 Participants
n=5 Participants
|
|
Mutation type
Exon 19+ ALK rearrangement
|
1 Participants
n=5 Participants
|
|
Mutation type
Exon 18 and Exon 20
|
1 Participants
n=5 Participants
|
|
Mutation type
None proven; met clinical criteria
|
2 Participants
n=5 Participants
|
|
Charlson Co-morbidity Index
|
6 units on a scale
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 months after Initiation of Stereostatic RadiotherapyProgression free survival (PFS) after locally ablative therapy and erlotinib in EGFR-mutant NSCLC patients who progressed on prior EGFR-tyrosine kinase inhibitor (TKI) therapy reported as percentage of participants who are alive and without progressive disease at 3 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or the appearance of new lesions.
Outcome measures
| Measure |
Stereotactic Radiosurgery Followed by Erlotinib
n=25 Participants
Stereotactic Radiosurgery or Other Local Ablation Followed by Erlotinib
Stereotactic Radiosurgery: 21 Gy daily for 5 days
Erlotinib: 150mg once daily
|
|---|---|
|
Percentage of Participants With Progression Free Survival
|
64 percentage of participants
Interval 42.5 to 82.0
|
SECONDARY outcome
Timeframe: Initiation of Stereotactic Radiotherapy every 6 to 12 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 monthsPopulation: 4 subjects were not evaluable for this outcome due to lack of follow-up measurements on ablated lesions
Count of subjects who had local control of sites previously progressive on erlotinib following SRS followed by erlotinib. Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), local control is defined as Complete Response (CR), Disappearance of all target lesions; or Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; in sites ablated by SRS.
Outcome measures
| Measure |
Stereotactic Radiosurgery Followed by Erlotinib
n=21 Participants
Stereotactic Radiosurgery or Other Local Ablation Followed by Erlotinib
Stereotactic Radiosurgery: 21 Gy daily for 5 days
Erlotinib: 150mg once daily
|
|---|---|
|
Percentage of Participants With Local Control of Sites on Erlotinib Following Stereotactic Radiosurgery (SRS)
|
7 Participants
|
SECONDARY outcome
Timeframe: up to 5 years after end of treatmentTo estimate overall survival (OS) after locally ablative therapy and erlotinib in EGFR-mutant, NSCLC patients who progressed on prior EGFR-TKI therapy measured as length of time from start of treatment until date of death from any cause
Outcome measures
| Measure |
Stereotactic Radiosurgery Followed by Erlotinib
n=25 Participants
Stereotactic Radiosurgery or Other Local Ablation Followed by Erlotinib
Stereotactic Radiosurgery: 21 Gy daily for 5 days
Erlotinib: 150mg once daily
|
|---|---|
|
Median Overall Survival
|
29 Months
Interval 21.7 to 36.3
|
SECONDARY outcome
Timeframe: From initiation to the end of SRS, up to 15 daysPopulation: Toxicities occurring in at least two participants from SRS are reported below
Toxicity of SRS will be measured by NCI CTCAE version 4 following completion of SRS, but prior to erlotinib re-initiation. The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Outcome measures
| Measure |
Stereotactic Radiosurgery Followed by Erlotinib
n=25 Participants
Stereotactic Radiosurgery or Other Local Ablation Followed by Erlotinib
Stereotactic Radiosurgery: 21 Gy daily for 5 days
Erlotinib: 150mg once daily
|
|---|---|
|
Toxicity Rate From Stereotactic Radiosurgery (SRS)
Fatigue · Grade 1
|
4 Participants
|
|
Toxicity Rate From Stereotactic Radiosurgery (SRS)
Fatigue · Grade 2
|
0 Participants
|
|
Toxicity Rate From Stereotactic Radiosurgery (SRS)
Fatigue · None
|
21 Participants
|
|
Toxicity Rate From Stereotactic Radiosurgery (SRS)
Pain · Grade 1
|
2 Participants
|
|
Toxicity Rate From Stereotactic Radiosurgery (SRS)
Pain · Grade 2
|
1 Participants
|
|
Toxicity Rate From Stereotactic Radiosurgery (SRS)
Pain · None
|
22 Participants
|
|
Toxicity Rate From Stereotactic Radiosurgery (SRS)
Anorexia · Grade 1
|
2 Participants
|
|
Toxicity Rate From Stereotactic Radiosurgery (SRS)
Anorexia · Grade 2
|
0 Participants
|
|
Toxicity Rate From Stereotactic Radiosurgery (SRS)
Anorexia · None
|
23 Participants
|
SECONDARY outcome
Timeframe: from end of SRS to end of erlotinib treatment (median duration of 5.7 months)Population: Toxicities grade 3 or higher and attributed to erlotinib re-treatment, or toxicities occurring in at least two participants are reported below
Toxicity of erlotinib will be graded using the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE version 4) which is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Outcome measures
| Measure |
Stereotactic Radiosurgery Followed by Erlotinib
n=25 Participants
Stereotactic Radiosurgery or Other Local Ablation Followed by Erlotinib
Stereotactic Radiosurgery: 21 Gy daily for 5 days
Erlotinib: 150mg once daily
|
|---|---|
|
Toxicity Rate Attributed to Erlotinib
Acneiform rash · Grade 1
|
5 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Acneiform rash · Grade 2
|
2 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Acneiform rash · Grade 3
|
2 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Acneiform rash · None
|
16 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Diarrhea · Grade 1
|
2 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Diarrhea · Grade 3
|
0 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Diarrhea · None
|
22 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Fatigue · Grade 1
|
2 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Fatigue · Grade 2
|
1 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Fatigue · Grade 3
|
0 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Fatigue · None
|
22 Participants
|
|
Toxicity Rate Attributed to Erlotinib
aspartate aminotransferase (AST) increased · Grade 1
|
2 Participants
|
|
Toxicity Rate Attributed to Erlotinib
aspartate aminotransferase (AST) increased · Grade 2
|
0 Participants
|
|
Toxicity Rate Attributed to Erlotinib
aspartate aminotransferase (AST) increased · Grade 3
|
0 Participants
|
|
Toxicity Rate Attributed to Erlotinib
aspartate aminotransferase (AST) increased · None
|
23 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Nausea · Grade 1
|
2 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Nausea · Grade 2
|
0 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Nausea · Grade 3
|
0 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Nausea · None
|
23 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Paronychia · Grade 1
|
2 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Paronychia · Grade 2
|
0 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Paronychia · Grade 3
|
0 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Paronychia · None
|
23 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Weight loss · Grade 1
|
2 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Weight loss · Grade 2
|
0 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Weight loss · Grade 3
|
0 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Weight loss · None
|
23 Participants
|
|
Toxicity Rate Attributed to Erlotinib
Diarrhea · Grade 2
|
1 Participants
|
Adverse Events
Stereotactic Radiosurgery Followed by Erlotinib
Serious adverse events
| Measure |
Stereotactic Radiosurgery Followed by Erlotinib
n=25 participants at risk
Stereotactic Radiosurgery or Other Local Ablation Followed by Erlotinib
Stereotactic Radiosurgery: 21 Gy daily for 5 days
Erlotinib: 150mg once daily
|
|---|---|
|
Injury, poisoning and procedural complications
Fracture
|
4.0%
1/25 • Number of events 2 • From start of treatment to date of death up to 60 months
|
|
Injury, poisoning and procedural complications
Fall
|
4.0%
1/25 • Number of events 1 • From start of treatment to date of death up to 60 months
|
Other adverse events
| Measure |
Stereotactic Radiosurgery Followed by Erlotinib
n=25 participants at risk
Stereotactic Radiosurgery or Other Local Ablation Followed by Erlotinib
Stereotactic Radiosurgery: 21 Gy daily for 5 days
Erlotinib: 150mg once daily
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
8.0%
2/25 • From start of treatment to date of death up to 60 months
|
|
Investigations
Alkaline phosphatase increased
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Metabolism and nutrition disorders
Anorexia
|
16.0%
4/25 • From start of treatment to date of death up to 60 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.0%
2/25 • From start of treatment to date of death up to 60 months
|
|
Investigations
Aspartate aminotransferase increased
|
12.0%
3/25 • From start of treatment to date of death up to 60 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.0%
5/25 • From start of treatment to date of death up to 60 months
|
|
Investigations
Blood bilirubin increased
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Eye disorders
Blurred vision
|
8.0%
2/25 • From start of treatment to date of death up to 60 months
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Injury, poisoning and procedural complications
Bruising
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Eye disorders
Conjunctivitis
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
24.0%
6/25 • From start of treatment to date of death up to 60 months
|
|
Psychiatric disorders
Depression
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Gastrointestinal disorders
Diarrhea
|
12.0%
3/25 • From start of treatment to date of death up to 60 months
|
|
Eye disorders
Dry eye
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
16.0%
4/25 • From start of treatment to date of death up to 60 months
|
|
Nervous system disorders
Dysgeusia
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Gastrointestinal disorders
Dyspepsia
|
12.0%
3/25 • From start of treatment to date of death up to 60 months
|
|
Gastrointestinal disorders
Dysphagia
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Ear and labyrinth disorders
Ear pain
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
General disorders
Edema face
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
General disorders
Edema limbs
|
8.0%
2/25 • From start of treatment to date of death up to 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
General disorders
Fatigue
|
32.0%
8/25 • From start of treatment to date of death up to 60 months
|
|
Eye disorders
Flashing lights
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
General disorders
Flu like symptoms
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Nervous system disorders
Headache
|
12.0%
3/25 • From start of treatment to date of death up to 60 months
|
|
Vascular disorders
Hot flashes
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
16.0%
4/25 • From start of treatment to date of death up to 60 months
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Metabolism and nutrition disorders
Hypernatremia
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
General disorders
Infusion site extravasation
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Psychiatric disorders
Insomnia
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Nervous system disorders
Lethargy
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Investigations
Lymphocyte count decreased
|
28.0%
7/25 • From start of treatment to date of death up to 60 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.0%
2/25 • From start of treatment to date of death up to 60 months
|
|
Skin and subcutaneous tissue disorders
Nail loss
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Skin and subcutaneous tissue disorders
Nail ridging
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Gastrointestinal disorders
Nausea
|
12.0%
3/25 • From start of treatment to date of death up to 60 months
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Investigations
Neutrophil count decreased
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
General disorders
Non-cardiac chest pain
|
12.0%
3/25 • From start of treatment to date of death up to 60 months
|
|
Gastrointestinal disorders
Oral hemorrhage
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
General disorders
Pain
|
12.0%
3/25 • From start of treatment to date of death up to 60 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
12.0%
3/25 • From start of treatment to date of death up to 60 months
|
|
Infections and infestations
Papulopustular rash
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Infections and infestations
Paronychia
|
8.0%
2/25 • From start of treatment to date of death up to 60 months
|
|
Investigations
Platelet count decreased
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
8.0%
2/25 • From start of treatment to date of death up to 60 months
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
20.0%
5/25 • From start of treatment to date of death up to 60 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
16.0%
4/25 • From start of treatment to date of death up to 60 months
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
|
8.0%
2/25 • From start of treatment to date of death up to 60 months
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Infections and infestations
Skin infection
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Infections and infestations
Upper respiratory infection
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Infections and infestations
Urinary tract infection
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Renal and urinary disorders
Urinary tract pain
|
8.0%
2/25 • From start of treatment to date of death up to 60 months
|
|
Renal and urinary disorders
Urinary urgency
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Gastrointestinal disorders
Vomiting
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
|
Eye disorders
Watering eyes
|
8.0%
2/25 • From start of treatment to date of death up to 60 months
|
|
Investigations
Weight loss
|
8.0%
2/25 • From start of treatment to date of death up to 60 months
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
8.0%
2/25 • From start of treatment to date of death up to 60 months
|
|
Investigations
White blood cell decreased
|
4.0%
1/25 • From start of treatment to date of death up to 60 months
|
Additional Information
Robin V. Johnson
UNC Lineberger Comprehensive Cancer Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place