Trial Outcomes & Findings for A Phase I/II Study of Ibrutinib in Previously Treated Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer (NCT NCT02321540)
NCT ID: NCT02321540
Last Updated: 2023-10-25
Results Overview
Number of DLT observed at dose levels 560 (starting dose) and 840 mg PO daily to determine the MTD using the 3+3 design.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
13 participants
Primary outcome timeframe
First cycle of 28 days
Results posted on
2023-10-25
Participant Flow
Participant milestones
| Measure |
Ibrutinib Dose Level 0
Participants received Ibrutinib at dose level 0 (560 mg PO daily) on a continuous basis on 28 day cycles.
|
Ibrutinib Dose Level 1
Participants received dose level 1 (840 mg PO daily) on a continuous basis on 28 day cycles.
|
|---|---|---|
|
Overall Study
STARTED
|
3
|
10
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
3
|
10
|
Reasons for withdrawal
| Measure |
Ibrutinib Dose Level 0
Participants received Ibrutinib at dose level 0 (560 mg PO daily) on a continuous basis on 28 day cycles.
|
Ibrutinib Dose Level 1
Participants received dose level 1 (840 mg PO daily) on a continuous basis on 28 day cycles.
|
|---|---|---|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Progression
|
3
|
9
|
Baseline Characteristics
A Phase I/II Study of Ibrutinib in Previously Treated Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Ibrutinib Dose Level 0
n=3 Participants
Participants received Ibrutinib at dose level 0 (560 mg PO daily on a continuous basis on 28 day cycles.
|
Ibrutinib Dose Level 1
n=10 Participants
Participants received Ibrutinib dose level 1 (840 mg PO daily) on a continuous basis on 28 day cycles.
|
Total
n=13 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
10 participants
n=7 Participants
|
13 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: First cycle of 28 daysPopulation: 12 patients were evaluable for overall response rate; 1 patient who received 840 mg PO daily was inevaluable due to death prior to first response assessment after start of treatment.
Number of DLT observed at dose levels 560 (starting dose) and 840 mg PO daily to determine the MTD using the 3+3 design.
Outcome measures
| Measure |
Ibrutinib Dose Level 0 (560mg)
n=3 Participants
Participants received Ibrutinib at dose level 0 (560 mg PO daily) on a continuous basis on 28 day cycles.
|
Ibrutinib Dose Level 1 (840mg)
n=10 Participants
Participants received Ibrutinib at dose level 1 (840 mg PO daily) on a continuous basis on 28 day cycles.
|
|---|---|---|
|
Number of Participants With at Least One Dose Limiting Toxicity (DLT) Observed During the Dose Escalation to Determine the Maximum Tolerated Dose (MTD)
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: after two cycles of therapy and every 8 weeks, up to 2 yearsPopulation: 12 patients were evaluable for overall response rate; 1 patient who received 840 mg PO daily was inevaluable due to death prior to first response assessment after start of treatment.
Complete response and partial resopnse rate RECIST 1.1 criteria The response was evaluated after two cycles of therapy and every 8 weeks until the first date that recurrent or progressive disease is objectively documented, up to 2 years.
Outcome measures
| Measure |
Ibrutinib Dose Level 0 (560mg)
n=3 Participants
Participants received Ibrutinib at dose level 0 (560 mg PO daily) on a continuous basis on 28 day cycles.
|
Ibrutinib Dose Level 1 (840mg)
n=9 Participants
Participants received Ibrutinib at dose level 1 (840 mg PO daily) on a continuous basis on 28 day cycles.
|
|---|---|---|
|
Overall Response Rate in Patients With EGFR Mutations Using RECIST
|
3 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: from start of treatment to time of progression or death, up to 2 yearsPopulation: 13 patients were followed up 12 patients were evaluable for disease control rate, duration of response and Response rate in patients with HER2 mutant non-small cell lung cancer; 1 patient who received 840 mg PO daily was inevaluable due to death prior to first response assessment after start of treatment.
Overall survival (OS) is defined as the duration of time from start of treatment to time of progression or death.
Outcome measures
| Measure |
Ibrutinib Dose Level 0 (560mg)
n=3 Participants
Participants received Ibrutinib at dose level 0 (560 mg PO daily) on a continuous basis on 28 day cycles.
|
Ibrutinib Dose Level 1 (840mg)
n=10 Participants
Participants received Ibrutinib at dose level 1 (840 mg PO daily) on a continuous basis on 28 day cycles.
|
|---|---|---|
|
Overall Survival (OS)
|
13.6 months
Interval 6.4 to 14.4
|
10.3 months
Interval 0.67 to 16.0
|
SECONDARY outcome
Timeframe: from start of treatment to time progression or death, whichever occurs first, up to 2 yearsPopulation: 13 patients were followed up 12 patients were evaluable for disease control rate, duration of response and Response rate in patients with HER2 mutant non-small cell lung cancer; 1 patient who received 840 mg PO daily was inevaluable due to death prior to first response assessment after start of treatment.
Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Outcome measures
| Measure |
Ibrutinib Dose Level 0 (560mg)
n=3 Participants
Participants received Ibrutinib at dose level 0 (560 mg PO daily) on a continuous basis on 28 day cycles.
|
Ibrutinib Dose Level 1 (840mg)
n=10 Participants
Participants received Ibrutinib at dose level 1 (840 mg PO daily) on a continuous basis on 28 day cycles.
|
|---|---|---|
|
Progression-Free Survival (PFS)
|
1.83 months
Interval 1.7 to 1.87
|
1.75 months
Interval 0.67 to 2.0
|
Adverse Events
Ibrutinib at Dose Level 0 (560 PO Daily).
Serious events: 0 serious events
Other events: 3 other events
Deaths: 3 deaths
Ibrutinib at Dose Level 1 (840 PO Daily).
Serious events: 4 serious events
Other events: 10 other events
Deaths: 10 deaths
Serious adverse events
| Measure |
Ibrutinib at Dose Level 0 (560 PO Daily).
n=3 participants at risk
Participants received Ibrutinib at dose level 0 (560 mg PO daily)
|
Ibrutinib at Dose Level 1 (840 PO Daily).
n=10 participants at risk
Participants received Ibrutinib at dose level 1 (840 mg PO daily)
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Cardiac disorders
Chest pain
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 2 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Psychiatric disorders
Confusion
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Nervous system disorders
Seizure
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
Other adverse events
| Measure |
Ibrutinib at Dose Level 0 (560 PO Daily).
n=3 participants at risk
Participants received Ibrutinib at dose level 0 (560 mg PO daily)
|
Ibrutinib at Dose Level 1 (840 PO Daily).
n=10 participants at risk
Participants received Ibrutinib at dose level 1 (840 mg PO daily)
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
20.0%
2/10 • Number of events 2 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
20.0%
2/10 • Number of events 4 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
40.0%
4/10 • Number of events 4 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
33.3%
1/3 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
0.00%
0/10 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Injury, poisoning and procedural complications
Bruising
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Infections and infestations
Burning with urination
|
33.3%
1/3 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
0.00%
0/10 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Buttock pain
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
General disorders
Chills
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
General disorders
Congestion of chest
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Gastrointestinal disorders
Constipation
|
66.7%
2/3 • Number of events 2 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
0.00%
0/10 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.3%
1/3 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
30.0%
3/10 • Number of events 7 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Investigations
Decreased chloride
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
40.0%
4/10 • Number of events 6 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Nervous system disorders
Dizziness
|
33.3%
1/3 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
0.00%
0/10 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
General disorders
Edema limbs
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 2 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Infections and infestations
Elevated UAWBC NCS
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
General disorders
Fatigue
|
66.7%
2/3 • Number of events 2 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
20.0%
2/10 • Number of events 2 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
General disorders
Fever
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Nervous system disorders
Headache
|
66.7%
2/3 • Number of events 2 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
0.00%
0/10 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
20.0%
2/10 • Number of events 2 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Vascular disorders
Hypertension
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
20.0%
2/10 • Number of events 2 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
20.0%
2/10 • Number of events 2 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Skin and subcutaneous tissue disorders
Mild dry rash a little on chest and arms
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Gastrointestinal disorders
Nausea
|
100.0%
3/3 • Number of events 3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
50.0%
5/10 • Number of events 6 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
30.0%
3/10 • Number of events 3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
General disorders
Pain
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
30.0%
3/10 • Number of events 3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Investigations
Platelet count decreased
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Skin and subcutaneous tissue disorders
Rash on legs and stomach
|
33.3%
1/3 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
0.00%
0/10 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
General disorders
General disorders and administration site conditions
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Tightness of upper left lung
|
33.3%
1/3 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
0.00%
0/10 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Renal and urinary disorders
Urinary frequency
|
33.3%
1/3 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
0.00%
0/10 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Renal and urinary disorders
Urinary tract infection
|
33.3%
1/3 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
0.00%
0/10 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Renal and urinary disorders
Urine output decreased
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Gastrointestinal disorders
Vomiting
|
100.0%
3/3 • Number of events 3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
50.0%
5/10 • Number of events 7 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
33.3%
1/3 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
0.00%
0/10 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
|
Renal and urinary disorders
Urinary tract pain
|
0.00%
0/3 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
10.0%
1/10 • Number of events 1 • From the first dose through 30 days after the last dose of study medication, up to 2 years
|
Additional Information
Dr. John V. Heymach, Chair, Thoracic-Head & Neck Med Onc
UT MD Anderson Cancer Center
Phone: (713) 792-6363
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place