Trial Outcomes & Findings for Concentration and Activity of Lapatinib in Vestibular Schwannomas (NCT NCT00863122)
NCT ID: NCT00863122
Last Updated: 2021-01-12
Results Overview
Steady-state plasma concentrations of lapatinib (ng/mL) at time of surgery, 10-13 days from starting drug.
COMPLETED
EARLY_PHASE1
26 participants
At time of surgery, 10-13 days from starting drug.
2021-01-12
Participant Flow
All patients undergoing surgery for vestibular schwannoma resection who met eligibility criteria were invited to participate
Patients could enroll on control (no drug) or lapatinib arms. 20 people were consented for the the lapatinib arm, but one patient withdrew consent prior to completion of eligibility screening and enrollment. So 19 patients enrolled on the lapatinib arm.
Participant milestones
| Measure |
Lapatinib
Subjects received lapatinib 1500 mg by mouth for 10 days prior to surgery for vestibular schwannoma resection.
|
Control
Control subjects did not receive any intervention prior to surgery for vestibular schwannoma resection.
|
|---|---|---|
|
Overall Study
STARTED
|
19
|
7
|
|
Overall Study
COMPLETED
|
19
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Per protocol, KPS was not recorded for control participants. Control participants agreed to donate tissue only. No clinical data was collected.
Baseline characteristics by cohort
| Measure |
Lapatinib
n=19 Participants
Subjects received lapatinib for 1500 mg by mouth daily for 10 days prior to surgery for vestibular schwannoma resection
|
Control
n=7 Participants
Control subjects did not receive any intervention prior to surgery for vestibular schwannoma resection
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=19 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=26 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
19 Participants
n=19 Participants
|
7 Participants
n=7 Participants
|
26 Participants
n=26 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=19 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=26 Participants
|
|
Age, Continuous
|
44 years
n=19 Participants
|
40 years
n=7 Participants
|
43.5 years
n=26 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=19 Participants
|
6 Participants
n=7 Participants
|
21 Participants
n=26 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=19 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=26 Participants
|
|
Region of Enrollment
United States
|
19 participants
n=19 Participants
|
7 participants
n=7 Participants
|
26 participants
n=26 Participants
|
|
Karnofsky Performance Status (KPS)
|
90 units on a scale (percent)
n=19 Participants • Per protocol, KPS was not recorded for control participants. Control participants agreed to donate tissue only. No clinical data was collected.
|
—
|
90 units on a scale (percent)
n=19 Participants • Per protocol, KPS was not recorded for control participants. Control participants agreed to donate tissue only. No clinical data was collected.
|
|
Patients with a diagnosis of NF2
|
9 participants
n=19 Participants
|
0 participants
n=7 Participants
|
9 participants
n=26 Participants
|
PRIMARY outcome
Timeframe: At time of surgery, 10-13 days from starting drug.Population: In the lapatinib group, 10 tissue and plasma samples were lost from analysis due to a freezer failure during a natural disaster denaturing the samples. 1 blood sample was contaminated, but tissue was available. Control group did not get any drug. A total of 8 participants of 19 given drug had data for analysis.
Steady-state plasma concentrations of lapatinib (ng/mL) at time of surgery, 10-13 days from starting drug.
Outcome measures
| Measure |
Lapatinib
n=8 Participants
Subjects received lapatinib 1500 mg by mouth for 10 days prior to surgery for vestibular schwannoma resection
|
Control
Control subjects will not receive any intervention prior to surgery for vestibular schwannoma resection. Control subjects donate tissue at the time of surgery.
|
|---|---|---|
|
Median Steady-state Lapatinib Plasma Concentrations at the Time of Surgical Resection
|
3149 ng/mL
Interval 786.0 to 5830.0
|
—
|
PRIMARY outcome
Timeframe: one yearPopulation: In the lapatinib group, 10 tissue and plasma samples were lost from analysis due to a freezer failure during a natural disaster denaturing the samples. Nine samples were available for tissue concentration assessment.
Count of tissue samples with lapatinib concentration \>3uM
Outcome measures
| Measure |
Lapatinib
n=9 Participants
Subjects received lapatinib 1500 mg by mouth for 10 days prior to surgery for vestibular schwannoma resection
|
Control
Control subjects will not receive any intervention prior to surgery for vestibular schwannoma resection. Control subjects donate tissue at the time of surgery.
|
|---|---|---|
|
To Assess Whether Lapatinib Can Reach a Minimum Tumor Concentration Level of >3uM in VS After Oral Dosing.
|
7 Participants
|
—
|
SECONDARY outcome
Timeframe: at time of surgeryPopulation: 10 lapatinib participants and 3 control participants did not have adequate tissue for analysis.
Assessed number of samples with high expression of phospho-ErbB2 in tissue at time of surgery
Outcome measures
| Measure |
Lapatinib
n=9 Participants
Subjects received lapatinib 1500 mg by mouth for 10 days prior to surgery for vestibular schwannoma resection
|
Control
n=4 Participants
Control subjects will not receive any intervention prior to surgery for vestibular schwannoma resection. Control subjects donate tissue at the time of surgery.
|
|---|---|---|
|
Assess the Level of ErbB2 Phosphorylation in VS.
|
5 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: At time of surgeryPopulation: The experiment to assess this outcome measure failed and no interpretable data could be collected.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: one yearPopulation: Of the nine participants in the lapatinib who had tumor available for analysis, four had a vestibular schwnannoma associated with a diagnosis of neurofibromatosis type 2 (NF2); five had sporadic vestibular schwannomas.
A comparison in the median lapatinib concentration (ng/g) in vestibular schwannomas associated with neurofibromatosis type 2 and sporadic vestibular schwannomas
Outcome measures
| Measure |
Lapatinib
n=4 Participants
Subjects received lapatinib 1500 mg by mouth for 10 days prior to surgery for vestibular schwannoma resection
|
Control
n=5 Participants
Control subjects will not receive any intervention prior to surgery for vestibular schwannoma resection. Control subjects donate tissue at the time of surgery.
|
|---|---|---|
|
Explore the Difference in the Concentration of Lapatinib Achieved in NF2-related Versus Idiopathic VS.
|
8367 ng/g
Interval 314.0 to 17821.0
|
4502 ng/g
Interval 1737.0 to 11712.0
|
SECONDARY outcome
Timeframe: at time of surgeryPopulation: 6 of the 7 participants had sporadic VS; 1 of 7 had NF2-associated VS. As such, we were unable to explore differences between the groups.
Due to the sample sizes, a comparison between sporadic and NF2-related vestibular schwannomas could not be made. Instead we report the mutational status.
Outcome measures
| Measure |
Lapatinib
n=7 Participants
Subjects received lapatinib 1500 mg by mouth for 10 days prior to surgery for vestibular schwannoma resection
|
Control
Control subjects will not receive any intervention prior to surgery for vestibular schwannoma resection. Control subjects donate tissue at the time of surgery.
|
|---|---|---|
|
Perform NF2 Gene Mutation Analysis Via Exon Scanning and MLPA as Well as Protein Expression in All VS and Explore Differences Between Sporadic and NF2 Related VS.
Hemizygous deletion in NF2 gene
|
4 Participants
|
—
|
|
Perform NF2 Gene Mutation Analysis Via Exon Scanning and MLPA as Well as Protein Expression in All VS and Explore Differences Between Sporadic and NF2 Related VS.
Homozygous deletion in NF2 gene
|
1 Participants
|
—
|
|
Perform NF2 Gene Mutation Analysis Via Exon Scanning and MLPA as Well as Protein Expression in All VS and Explore Differences Between Sporadic and NF2 Related VS.
No deletion in NF2 gene
|
2 Participants
|
—
|
Adverse Events
Lapatinib
Control
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Lapatinib
n=19 participants at risk
Subjects received lapatinib 1500 mg by mouth for 10 days prior to surgery for vestibular schwannoma resection.
|
Control
Control subjects will not receive any intervention prior to surgery for vestibular schwannoma resection. Control subjects donate tissue at the time of surgery. AEs were not collected in this group as there was no study intervention (i.e. they did not take the drug).
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Rash
|
31.6%
6/19 • Number of events 6
Zero participants were At Risk from the Control arm since they did not receive any intervention.
|
—
0/0
Zero participants were At Risk from the Control arm since they did not receive any intervention.
|
|
Gastrointestinal disorders
Diarrhea
|
36.8%
7/19 • Number of events 7
Zero participants were At Risk from the Control arm since they did not receive any intervention.
|
—
0/0
Zero participants were At Risk from the Control arm since they did not receive any intervention.
|
|
General disorders
Fatigue
|
21.1%
4/19 • Number of events 4
Zero participants were At Risk from the Control arm since they did not receive any intervention.
|
—
0/0
Zero participants were At Risk from the Control arm since they did not receive any intervention.
|
|
Gastrointestinal disorders
Nausea
|
21.1%
4/19 • Number of events 4
Zero participants were At Risk from the Control arm since they did not receive any intervention.
|
—
0/0
Zero participants were At Risk from the Control arm since they did not receive any intervention.
|
|
Skin and subcutaneous tissue disorders
Acne
|
10.5%
2/19 • Number of events 2
Zero participants were At Risk from the Control arm since they did not receive any intervention.
|
—
0/0
Zero participants were At Risk from the Control arm since they did not receive any intervention.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60