Trial Outcomes & Findings for Phase I/II of Oral Vorinostat Combination With Erlotinib in NSCLC Patients With EGFR Mutations With DP After Erlotinib. (NCT NCT00503971)
NCT ID: NCT00503971
Last Updated: 2025-03-07
Results Overview
Progression Free Survival was defined as time from first treatment until progression or death from any cause.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
33 participants
Primary outcome timeframe
From date of first day of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 weeks
Results posted on
2025-03-07
Participant Flow
Between December 2007 and November 2010 the patients were enrolled in the phase I-II trial.
Screening details: Histologically confirmed NSCLC Diagnosis of advanced stage IIIB with pleural effusion or IV NSCLC Previous disease progression after \>= 3 months treatment with Erlotinib. Must tolerate erlotinib dose of 150 mg daily during the prior month. Have demonstrated mutations at epidermal growth factor receptor (EGFR) at Exon 19 or Exon 21
Participant milestones
| Measure |
Vorinostat Plus Erlotinib Phase II
Vorinostat plus Erlotinib
Phase II:
400 mg Vorinostat d1-7 and 15-21 every 28 days plus 150 mg Erlotinib daily per cycle
|
Vorinostat Plus Erlotinib Phase I Level 1
Phase I:
Dose level 1: 300 mg V d1-7 every 21 days plus 100 mg E daily If none of the patient experienced dose limiting toxicity, the next dose level was started.
|
Vorinostat Plus Erlotinib Phase I Level 2
Dose level 2: 400 mg V d1-7 every 21 days plus 100 mg E daily Dose level 2b: 300 mg V d1-7 and 15-21 every 28 days plus 100 mg E daily
If none of the patient experienced dose limiting toxicity, the next dose level was started.
|
Vorinostat Plus Erlotinib Phase I Level 3
Dose level 3: 400 mg V d1-7 and 15-21 every 28 days plus 150 mg E daily
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
25
|
3
|
3
|
2
|
|
Overall Study
COMPLETED
|
25
|
3
|
3
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase I/II of Oral Vorinostat Combination With Erlotinib in NSCLC Patients With EGFR Mutations With DP After Erlotinib.
Baseline characteristics by cohort
| Measure |
Vorinostat Plus Erlotinib Phase II
n=25 Participants
Vorinostat plus erlotinib
Phase II:
Dose level 3: 400 mg V d1-7 and 15-21 every 28 days plus 150 mg E daily
|
Vorinostat Plus Erlotinib Phase I
n=3 Participants
Drug: Vorinostat plus Erlotinib
Phase I:
Dose level 1: 300 mg V d1-7 every 21 days plus 100 mg E daily
|
Vorinostat Plus Erlotinib Phase I Level 2
n=3 Participants
Drug: Vorinostat plus Erlotinib
Phase I:
Dose level 2: 400 mg V d1-7 every 21 days plus 100 mg E daily Dose level 2b: 300 mg V d1-7 and 15-21 every 28 days plus 100 mg E daily
|
Vorinostat Plus Erlotinib Phase I Level 3
n=2 Participants
Drug: Vorinostat plus Erlotinib
Phase I:
Dose level 3: 400 mg V d1-7 and 15-21 every 28 days plus 150 mg E daily
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
60.8 years
STANDARD_DEVIATION 10.10 • n=99 Participants
|
60 years
STANDARD_DEVIATION 9.93 • n=107 Participants
|
54.67 years
STANDARD_DEVIATION 9.74 • n=206 Participants
|
65 years
STANDARD_DEVIATION 12 • n=7 Participants
|
60.12 years
STANDARD_DEVIATION 10.44 • n=31 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
19 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
14 Participants
n=31 Participants
|
|
Region of Enrollment
Spain
|
25 participants
n=99 Participants
|
3 participants
n=107 Participants
|
3 participants
n=206 Participants
|
2 participants
n=7 Participants
|
33 participants
n=31 Participants
|
|
ECOG
ECOG 0
|
8 participants
n=99 Participants
|
2 participants
n=107 Participants
|
2 participants
n=206 Participants
|
1 participants
n=7 Participants
|
13 participants
n=31 Participants
|
|
ECOG
ECOG 1
|
15 participants
n=99 Participants
|
1 participants
n=107 Participants
|
1 participants
n=206 Participants
|
1 participants
n=7 Participants
|
18 participants
n=31 Participants
|
|
ECOG
ECOG 2
|
2 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
2 participants
n=31 Participants
|
|
Smoking habits
Current
|
3 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
3 participants
n=31 Participants
|
|
Smoking habits
Former > 5 years
|
4 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
4 participants
n=31 Participants
|
|
Smoking habits
Former 1-5 years
|
1 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
1 participants
n=31 Participants
|
|
Smoking habits
Former < 1 year
|
1 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
1 participants
n=31 Participants
|
|
Smoking habits
Never
|
16 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
16 participants
n=31 Participants
|
|
Smoking habits
Not recorded
|
0 participants
n=99 Participants
|
3 participants
n=107 Participants
|
3 participants
n=206 Participants
|
2 participants
n=7 Participants
|
8 participants
n=31 Participants
|
|
Stage
IIIB
|
1 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
1 participants
n=31 Participants
|
|
Stage
IV
|
24 participants
n=99 Participants
|
3 participants
n=107 Participants
|
3 participants
n=206 Participants
|
2 participants
n=7 Participants
|
32 participants
n=31 Participants
|
|
Histology
Adenocarcinoma
|
21 participants
n=99 Participants
|
3 participants
n=107 Participants
|
3 participants
n=206 Participants
|
2 participants
n=7 Participants
|
29 participants
n=31 Participants
|
|
Histology
Squamous
|
2 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
2 participants
n=31 Participants
|
|
Histology
Large cell
|
2 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
2 participants
n=31 Participants
|
|
Metastatic sites
One
|
5 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
5 participants
n=31 Participants
|
|
Metastatic sites
Two
|
10 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
10 participants
n=31 Participants
|
|
Metastatic sites
Three or more
|
10 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
10 participants
n=31 Participants
|
|
Metastatic sites
Not recorded
|
0 participants
n=99 Participants
|
3 participants
n=107 Participants
|
3 participants
n=206 Participants
|
2 participants
n=7 Participants
|
8 participants
n=31 Participants
|
|
EGFR tumor mutations
Del 19
|
15 participants
n=99 Participants
|
2 participants
n=107 Participants
|
2 participants
n=206 Participants
|
2 participants
n=7 Participants
|
21 participants
n=31 Participants
|
|
EGFR tumor mutations
L858R
|
10 participants
n=99 Participants
|
1 participants
n=107 Participants
|
1 participants
n=206 Participants
|
0 participants
n=7 Participants
|
12 participants
n=31 Participants
|
|
EGFR mutations blood
Del 19
|
7 participants
n=99 Participants
|
3 participants
n=107 Participants
|
2 participants
n=206 Participants
|
1 participants
n=7 Participants
|
13 participants
n=31 Participants
|
|
EGFR mutations blood
L858R
|
5 participants
n=99 Participants
|
0 participants
n=107 Participants
|
1 participants
n=206 Participants
|
1 participants
n=7 Participants
|
7 participants
n=31 Participants
|
|
EGFR mutations blood
Wild type
|
6 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
6 participants
n=31 Participants
|
|
EGFR mutations blood
NE
|
7 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
7 participants
n=31 Participants
|
|
T790M blood
Positive
|
7 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
7 participants
n=31 Participants
|
|
T790M blood
Wild type
|
11 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
11 participants
n=31 Participants
|
|
T790M blood
NE
|
7 participants
n=99 Participants
|
3 participants
n=107 Participants
|
3 participants
n=206 Participants
|
2 participants
n=7 Participants
|
15 participants
n=31 Participants
|
|
Median prior treatments
One
|
7 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
7 participants
n=31 Participants
|
|
Median prior treatments
Two
|
4 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
4 participants
n=31 Participants
|
|
Median prior treatments
Three
|
8 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
8 participants
n=31 Participants
|
|
Median prior treatments
Four or more
|
6 participants
n=99 Participants
|
0 participants
n=107 Participants
|
0 participants
n=206 Participants
|
0 participants
n=7 Participants
|
6 participants
n=31 Participants
|
|
Median prior treatments
Not recorded
|
0 participants
n=99 Participants
|
3 participants
n=107 Participants
|
3 participants
n=206 Participants
|
2 participants
n=7 Participants
|
8 participants
n=31 Participants
|
PRIMARY outcome
Timeframe: From date of first day of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 weeksPopulation: Efficacy analysis PFSR12w population: all patients who have received at least one dose of study medication have been included.
Progression Free Survival was defined as time from first treatment until progression or death from any cause.
Outcome measures
| Measure |
Vorinostat Plus Erlotinib Phase II
n=22 Participants
Vorinostat plus erlotinib
Phase II:
Dose level 3: 400 mg V d1-7 and 15-21 every 28 days plus 150 mg E daily
|
|---|---|
|
Progression Free Survival Rate at 12 Weeks
|
28 percentage of participants
Interval 18.0 to 37.2
|
PRIMARY outcome
Timeframe: Up to 24 weeks for each dosing cohortPopulation: Fourteen patients were treated with escalation doses of vorinostat.
In the phase I, a classic 3 + 3 dose escalation method with 3 patients treated initially at each dose level was used. MTD was determined by testing on dose escalation cohorts: continuous full dose of erlotinib 150 mg orally (p.o.) in a daily administration(QD) and escalating doses of vorinostat p.o. at three dose levels:300 mg QD 7 days every 21 days, 400 mg QD 7 days every 21 days,and 400 mg QD, 7 days every other week. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in less than or equal to 1 in 6 patients. DLTs were defined as any Vorinostat-related Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE 3.0) Grade 3 or 4 adverse events.
Outcome measures
| Measure |
Vorinostat Plus Erlotinib Phase II
n=14 Participants
Vorinostat plus erlotinib
Phase II:
Dose level 3: 400 mg V d1-7 and 15-21 every 28 days plus 150 mg E daily
|
|---|---|
|
Maximum Tolerated Dose (MTD) of Oral Vorinostat Phase I
|
400 mg
|
SECONDARY outcome
Timeframe: From the date of study inclusion until end of follow up, up to 36 months.Population: Efficacy analysis: all patients who have received at least one dose of study medication have been included.
Overall survival was defined as time from study inclusion until death
Outcome measures
| Measure |
Vorinostat Plus Erlotinib Phase II
n=25 Participants
Vorinostat plus erlotinib
Phase II:
Dose level 3: 400 mg V d1-7 and 15-21 every 28 days plus 150 mg E daily
|
|---|---|
|
Overall Survival
|
10.3 Month
Interval 2.4 to 18.1
|
SECONDARY outcome
Timeframe: From the date of randomization until end of follow up, up to 36 months.Population: Efficacy analysis: all patients who have received at least one dose of study medication have been included.
The time to progression has been defined as the time that elapses, in months, since the patient begins study treatment until the patient progresses or dies from the disease, the first thing that occurs. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Outcome measures
| Measure |
Vorinostat Plus Erlotinib Phase II
n=25 Participants
Vorinostat plus erlotinib
Phase II:
Dose level 3: 400 mg V d1-7 and 15-21 every 28 days plus 150 mg E daily
|
|---|---|
|
Time to Progression
|
1.8 Month
Interval 1.7 to 2.0
|
Adverse Events
Vorinostat Plus Erlotinib Phase II
Serious events: 16 serious events
Other events: 22 other events
Deaths: 1 deaths
Vorinostat Plus Erlotinib Phase I Dose Level 1
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Vorinostat Plus Erlotinib Phase I Dose Level 2
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Vorinostat Plus Erlotinib Phase I Dose Level 3
Serious events: 2 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vorinostat Plus Erlotinib Phase II
n=25 participants at risk
Vorinostat plus erlotinib
Phase II:
Dose level 3: 400 mg V d1-7 and 15-21 every 28 days plus 150 mg E daily
|
Vorinostat Plus Erlotinib Phase I Dose Level 1
n=3 participants at risk
Dose level 1: 300 mg V d1-7 every 21 days plus 100 mg E daily If none of the patient experienced dose limiting toxicity, the next dose level was started.
|
Vorinostat Plus Erlotinib Phase I Dose Level 2
n=3 participants at risk
Dose level 2: 400 mg V d1-7 every 21 days plus 100 mg E daily Dose level 2b: 300 mg V d1-7 and 15-21 every 28 days plus 100 mg E daily. If none of the patient experienced dose limiting toxicity, the next dose level was started.
|
Vorinostat Plus Erlotinib Phase I Dose Level 3
n=2 participants at risk
Dose level 3: 400 mg V d1-7 and 15-21 every 28 days plus 150 mg E daily
|
|---|---|---|---|---|
|
General disorders
Fatigue
|
24.0%
6/25 • Number of events 6 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/3 • 37 months
|
50.0%
1/2 • Number of events 1 • 37 months
|
|
General disorders
Fever
|
4.0%
1/25 • Number of events 1 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/2 • 37 months
|
|
Gastrointestinal disorders
Diarrhea
|
12.0%
3/25 • Number of events 3 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/3 • 37 months
|
50.0%
1/2 • Number of events 1 • 37 months
|
|
Metabolism and nutrition disorders
Anorexia
|
20.0%
5/25 • Number of events 5 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/2 • 37 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumopathy
|
4.0%
1/25 • Number of events 1 • 37 months
|
0.00%
0/3 • 37 months
|
—
0/0 • 37 months
|
0.00%
0/2 • 37 months
|
|
Gastrointestinal disorders
Mucositis
|
0.00%
0/25 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/3 • 37 months
|
50.0%
1/2 • Number of events 1 • 37 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/25 • 37 months
|
0.00%
0/3 • 37 months
|
33.3%
1/3 • Number of events 1 • 37 months
|
0.00%
0/2 • 37 months
|
Other adverse events
| Measure |
Vorinostat Plus Erlotinib Phase II
n=25 participants at risk
Vorinostat plus erlotinib
Phase II:
Dose level 3: 400 mg V d1-7 and 15-21 every 28 days plus 150 mg E daily
|
Vorinostat Plus Erlotinib Phase I Dose Level 1
n=3 participants at risk
Dose level 1: 300 mg V d1-7 every 21 days plus 100 mg E daily If none of the patient experienced dose limiting toxicity, the next dose level was started.
|
Vorinostat Plus Erlotinib Phase I Dose Level 2
n=3 participants at risk
Dose level 2: 400 mg V d1-7 every 21 days plus 100 mg E daily Dose level 2b: 300 mg V d1-7 and 15-21 every 28 days plus 100 mg E daily. If none of the patient experienced dose limiting toxicity, the next dose level was started.
|
Vorinostat Plus Erlotinib Phase I Dose Level 3
n=2 participants at risk
Dose level 3: 400 mg V d1-7 and 15-21 every 28 days plus 150 mg E daily
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
8.0%
2/25 • Number of events 2 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/2 • 37 months
|
|
Blood and lymphatic system disorders
Anemia
|
80.0%
20/25 • Number of events 20 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/3 • 37 months
|
100.0%
2/2 • Number of events 2 • 37 months
|
|
Blood and lymphatic system disorders
Leukopenia
|
12.0%
3/25 • Number of events 3 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/2 • 37 months
|
|
Blood and lymphatic system disorders
Lymphopenia
|
8.0%
2/25 • Number of events 2 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/3 • 37 months
|
50.0%
1/2 • Number of events 1 • 37 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
12.0%
3/25 • Number of events 3 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/2 • 37 months
|
|
Eye disorders
Ocular toxicity
|
20.0%
5/25 • Number of events 5 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/2 • 37 months
|
|
General disorders
Fatigue
|
64.0%
16/25 • Number of events 16 • 37 months
|
66.7%
2/3 • Number of events 2 • 37 months
|
33.3%
1/3 • Number of events 1 • 37 months
|
100.0%
2/2 • Number of events 2 • 37 months
|
|
General disorders
Asthenia
|
40.0%
10/25 • Number of events 10 • 37 months
|
66.7%
2/3 • Number of events 2 • 37 months
|
33.3%
1/3 • Number of events 1 • 37 months
|
100.0%
2/2 • Number of events 2 • 37 months
|
|
General disorders
Anorexy
|
36.0%
9/25 • Number of events 9 • 37 months
|
0.00%
0/3 • 37 months
|
66.7%
2/3 • Number of events 2 • 37 months
|
100.0%
2/2 • Number of events 2 • 37 months
|
|
General disorders
Fever
|
8.0%
2/25 • Number of events 2 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/3 • 37 months
|
50.0%
1/2 • Number of events 1 • 37 months
|
|
Gastrointestinal disorders
Diarrhea
|
80.0%
20/25 • Number of events 20 • 37 months
|
66.7%
2/3 • Number of events 2 • 37 months
|
66.7%
2/3 • Number of events 2 • 37 months
|
100.0%
2/2 • Number of events 2 • 37 months
|
|
Gastrointestinal disorders
Vomiting
|
36.0%
9/25 • Number of events 9 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/3 • 37 months
|
100.0%
2/2 • Number of events 2 • 37 months
|
|
Gastrointestinal disorders
Epigastralgia
|
16.0%
4/25 • Number of events 4 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/3 • 37 months
|
100.0%
2/2 • Number of events 2 • 37 months
|
|
Gastrointestinal disorders
Xerostomia
|
24.0%
6/25 • Number of events 6 • 37 months
|
66.7%
2/3 • Number of events 2 • 37 months
|
66.7%
2/3 • Number of events 2 • 37 months
|
100.0%
2/2 • Number of events 2 • 37 months
|
|
Gastrointestinal disorders
Mucositis
|
12.0%
3/25 • Number of events 3 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/3 • 37 months
|
0.00%
0/2 • 37 months
|
|
Renal and urinary disorders
Creatinine elevation
|
8.0%
2/25 • Number of events 2 • 37 months
|
0.00%
0/3 • 37 months
|
33.3%
1/3 • Number of events 1 • 37 months
|
100.0%
2/2 • Number of events 2 • 37 months
|
|
Hepatobiliary disorders
Hyperbilirubinemia
|
8.0%
2/25 • Number of events 2 • 37 months
|
33.3%
1/3 • Number of events 1 • 37 months
|
0.00%
0/3 • 37 months
|
100.0%
2/2 • Number of events 2 • 37 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
48.0%
12/25 • Number of events 12 • 37 months
|
33.3%
1/3 • Number of events 1 • 37 months
|
33.3%
1/3 • Number of events 1 • 37 months
|
100.0%
2/2 • Number of events 2 • 37 months
|
|
Skin and subcutaneous tissue disorders
Xeroderma
|
32.0%
8/25 • Number of events 8 • 37 months
|
66.7%
2/3 • Number of events 2 • 37 months
|
66.7%
2/3 • Number of events 2 • 37 months
|
100.0%
2/2 • Number of events 2 • 37 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place