Trial Outcomes & Findings for A Study Of Oral GW572016 In Advanced Or Metastatic Non-Small Cell Lung Cancer (NCT NCT00073008)
NCT ID: NCT00073008
Last Updated: 2017-02-28
Results Overview
Disease progression and tumor response (number of participants achieving a complete response \[CR\] or partial response \[PR\]), using standardized criteria (Response evaluation criteria in solid tumors). CR, disappearance of all target lesions; PR, 30% decrease in the sum of the longest diameter of target lesions; progressive disease, 20% increase in the sum of the longest diameter of target lesions; stable disease, small changes that do not meet above criteria. Disease assessment was done at baseline and then every 8 weeks after starting treatment, until the participant discontinued treatment.
TERMINATED
PHASE2
131 participants
Baseline and then every 8 weeks through end of treatment
2017-02-28
Participant Flow
Participant milestones
| Measure |
Lapatinib 1500 mg QD
Oral lapatinib 1500 mg once daily (QD)
|
Lapatinib 500 mg BID
Oral lapatinib 500 mg twice daily (BID)
|
|---|---|---|
|
Overall Study
STARTED
|
65
|
66
|
|
Overall Study
COMPLETED
|
3
|
3
|
|
Overall Study
NOT COMPLETED
|
62
|
63
|
Reasons for withdrawal
| Measure |
Lapatinib 1500 mg QD
Oral lapatinib 1500 mg once daily (QD)
|
Lapatinib 500 mg BID
Oral lapatinib 500 mg twice daily (BID)
|
|---|---|---|
|
Overall Study
Missing
|
6
|
6
|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
3
|
|
Overall Study
Death
|
46
|
47
|
|
Overall Study
"Other" selected on Case Report Form
|
7
|
5
|
Baseline Characteristics
A Study Of Oral GW572016 In Advanced Or Metastatic Non-Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Lapatinib 1500 mg QD
n=65 Participants
Oral lapatinib 1500 mg once daily (QD)
|
Lapatinib 500 mg BID
n=66 Participants
Oral lapatinib 500 mg twice daily (BID)
|
Total
n=131 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.1 years
STANDARD_DEVIATION 12.03 • n=5 Participants
|
65.2 years
STANDARD_DEVIATION 10.56 • n=7 Participants
|
65.1 years
STANDARD_DEVIATION 11.27 • n=5 Participants
|
|
Gender
Female
|
33 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
|
Gender
Male
|
32 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
58 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
54 participants
n=5 Participants
|
56 participants
n=7 Participants
|
110 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
4 participants
n=5 Participants
|
1 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
4 participants
n=5 Participants
|
5 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Hispanic
|
2 participants
n=5 Participants
|
4 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Histology at diagnosis
Squamous cell
|
9 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Histology at diagnosis
Bronchioloalveolar carcinoma (BAC)
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Histology at diagnosis
Adenocarcinoma with BAC features
|
8 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Histology at diagnosis
Adenocarcinoma without BAC features
|
34 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
|
Histology at diagnosis
Other non-small cell lung cancer type
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Histology at diagnosis
Other
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Histology at diagnosis
Missing
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and then every 8 weeks through end of treatmentPopulation: Targeted Population: all randomized participants who received at least one dose of study drug and had either the histological subtypes of adenocarcinoma with bronchioloalveolar carcinoma features or pure bronchioloalveolar carcinoma, or were never smokers with any histology of non-small cell lung cancer (NSCLC)
Disease progression and tumor response (number of participants achieving a complete response \[CR\] or partial response \[PR\]), using standardized criteria (Response evaluation criteria in solid tumors). CR, disappearance of all target lesions; PR, 30% decrease in the sum of the longest diameter of target lesions; progressive disease, 20% increase in the sum of the longest diameter of target lesions; stable disease, small changes that do not meet above criteria. Disease assessment was done at baseline and then every 8 weeks after starting treatment, until the participant discontinued treatment.
Outcome measures
| Measure |
Lapatinib 1500 mg QD
n=24 Participants
Oral lapatinib 1500 mg once daily (QD)
|
Lapatinib 500 mg BID
n=32 Participants
Oral lapatinib 500 mg twice daily (BID)
|
|---|---|---|
|
Tumor Response in the Targeted Population Through the End of Treatment
Complete response
|
0 participants
|
0 participants
|
|
Tumor Response in the Targeted Population Through the End of Treatment
Partial response
|
0 participants
|
0 participants
|
|
Tumor Response in the Targeted Population Through the End of Treatment
Stable disease
|
5 participants
|
9 participants
|
|
Tumor Response in the Targeted Population Through the End of Treatment
Progressive disease
|
18 participants
|
20 participants
|
|
Tumor Response in the Targeted Population Through the End of Treatment
Missing
|
1 participants
|
3 participants
|
SECONDARY outcome
Timeframe: From randomization and then every 8 weeks up to four monthsPopulation: Targeted Population
Percentage of participants in the Targeted Population, at 4 months after starting study drug, who were alive and without disease progression.
Outcome measures
| Measure |
Lapatinib 1500 mg QD
n=24 Participants
Oral lapatinib 1500 mg once daily (QD)
|
Lapatinib 500 mg BID
n=32 Participants
Oral lapatinib 500 mg twice daily (BID)
|
|---|---|---|
|
Progression-free Survival (PFS) at Four Months in the Targeted Population
|
34.5 percentage of participants
|
19.7 percentage of participants
|
SECONDARY outcome
Timeframe: From randomization and then every 8 weeks up to four monthsPopulation: Non-Targeted Population: all randomized participants who received at least one dose of study drug but who did not meet the criteria for inclusion in the Targeted Population.
Percentage of participants in the Non-Targeted Population, at 4 months after starting study drug, who were alive and without disease progression.
Outcome measures
| Measure |
Lapatinib 1500 mg QD
n=41 Participants
Oral lapatinib 1500 mg once daily (QD)
|
Lapatinib 500 mg BID
n=34 Participants
Oral lapatinib 500 mg twice daily (BID)
|
|---|---|---|
|
Progression-free Survival (PFS) at Four Months in the Non-Targeted Population
|
27.1 percentage of participants
|
18.3 percentage of participants
|
SECONDARY outcome
Timeframe: From randomization to disease progression (for serum biomarkers) or until analyses of tumor tissue samplesTo further characterize the participant population, these biomarkers could be tested: serum levels of ErbB1 and ErbB2; intra-tumoral expression of ErbB1, ErbB2, etc.; mutations in ErbB1, ErbB2, and k-ras. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, serum biomarkers were not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From randomization to time of PK period completed: Day 1 (first dose) and Days 2, 28, and 29 while participant was on study drugTo characterize the PK (absorption, distribution, metabolism, and excretion) of the study drug lapatinib in the participant population. PK is defined as the concentration of drug in a participant's blood at certain time points after the drug was taken by mouth. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, pharmacokinetics were not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From randomization at every 4-week assessment through end of treatmentTo (1) investigate the relationship between genetic variants in specific genes and the absorption, distribution, metabolism, and excretion (pharmacokinetics) of lapatinib, and to (2) investigate the relationship between genetic variants in select genes in DNA and the response (safety, efficacy, and tolerability) to lapatinib. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, pharmacogenetics were not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and then every 4 weeks through end of treatmentStandard survey forms were completed by the participant at scheduled assessments to find out how the participant felt while on study. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, quality of life was not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From randomization and then every 8 weeks to time of response to study drugTime from randomization until first documented evidence of partial or complete tumor response, measured using standard criteria (RECIST). Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, time to response was not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time from first documented evidence of response to study treatment and then every 8 weeks until disease progression or deathFor those participants who show a complete or partial response, duration of response would be time from first documented evidence of response (complete or partial response by RECIST) until disease progression or death, if sooner. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, duration of response was not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From randomization and then every 8 weeks to disease progression or deathTime from randomization until the first documented sign of disease progression or death due to any cause, if sooner. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, time to tumor progression was not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From randomization and then every 8 weeks while on study drug and then every 3 months as follow-up until deathOverall survival is measured as the time from randomization until death due to any cause. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, overall survival was not analyzed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Anytime from Baseline through end of studyComparison of the specific cell type (histology) of non-small cell lung cancer from participant's tissue samples, as determined by local pathologist, to the type determined by an independent pathologist. Based on the interim analysis at the end of Stage 1, and predefined stopping rules for futility, further enrollment into the study was stopped due to lack of efficacy on both treatment arms; therefore, NSCLC histology was not analyzed.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and then every 8 weeks through end of treatmentPopulation: Non-Targeted Population: all randomized participants who received at least one dose of study drug but who did not meet the criteria for inclusion in the Targeted Population.
Baseline and then every 8 weeks through end of treatment (end of treatment for each participant was dependent on when the participant withdrew from study therapy due to disease progression, an adverse event or participant decision)
Outcome measures
| Measure |
Lapatinib 1500 mg QD
n=41 Participants
Oral lapatinib 1500 mg once daily (QD)
|
Lapatinib 500 mg BID
n=34 Participants
Oral lapatinib 500 mg twice daily (BID)
|
|---|---|---|
|
Tumor Response in the Non-Targeted Population Through the End of Treatment
Complete response
|
0 participants
|
0 participants
|
|
Tumor Response in the Non-Targeted Population Through the End of Treatment
Partial response
|
1 participants
|
0 participants
|
|
Tumor Response in the Non-Targeted Population Through the End of Treatment
Stable disease
|
10 participants
|
6 participants
|
|
Tumor Response in the Non-Targeted Population Through the End of Treatment
Progressive disease
|
27 participants
|
25 participants
|
|
Tumor Response in the Non-Targeted Population Through the End of Treatment
Missing
|
3 participants
|
3 participants
|
Adverse Events
Lapatinib 1500 mg QD
Lapatinib 500 mg BID
Serious adverse events
| Measure |
Lapatinib 1500 mg QD
n=65 participants at risk
Oral lapatinib 1500 mg once daily (QD)
|
Lapatinib 500 mg BID
n=66 participants at risk
Oral lapatinib 500 mg twice daily (BID)
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.5%
1/65
|
7.6%
5/66
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
1.5%
1/65
|
1.5%
1/66
|
|
Cardiac disorders
Pleural effusion
|
3.1%
2/65
|
0.00%
0/66
|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
0.00%
0/65
|
1.5%
1/66
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/65
|
1.5%
1/66
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
0.00%
0/65
|
1.5%
1/66
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hemorrhage
|
0.00%
0/65
|
1.5%
1/66
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/65
|
1.5%
1/66
|
|
Gastrointestinal disorders
Diarrhea
|
4.6%
3/65
|
0.00%
0/66
|
|
Gastrointestinal disorders
Nausea
|
1.5%
1/65
|
3.0%
2/66
|
|
Gastrointestinal disorders
Vomiting
|
1.5%
1/65
|
3.0%
2/66
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/65
|
1.5%
1/66
|
|
Gastrointestinal disorders
Constipation
|
1.5%
1/65
|
0.00%
0/66
|
|
Gastrointestinal disorders
Diarrhea hemorrhagic
|
0.00%
0/65
|
1.5%
1/66
|
|
Gastrointestinal disorders
Ileus
|
1.5%
1/65
|
0.00%
0/66
|
|
Cardiac disorders
Atrial fibrillation
|
3.1%
2/65
|
0.00%
0/66
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/65
|
1.5%
1/66
|
|
Cardiac disorders
Cardiac tamponade
|
1.5%
1/65
|
0.00%
0/66
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/65
|
1.5%
1/66
|
|
Infections and infestations
Pneumonia
|
1.5%
1/65
|
1.5%
1/66
|
|
Infections and infestations
Sepsis
|
0.00%
0/65
|
1.5%
1/66
|
|
Infections and infestations
Urinary tract infection
|
1.5%
1/65
|
0.00%
0/66
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.5%
1/65
|
0.00%
0/66
|
|
Metabolism and nutrition disorders
Dehydration
|
1.5%
1/65
|
0.00%
0/66
|
|
Metabolism and nutrition disorders
Fluid overload
|
0.00%
0/65
|
1.5%
1/66
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
1.5%
1/65
|
0.00%
0/66
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/65
|
1.5%
1/66
|
|
Renal and urinary disorders
Nephrolithiasis
|
1.5%
1/65
|
0.00%
0/66
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/65
|
1.5%
1/66
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/65
|
1.5%
1/66
|
|
General disorders
Asthenia
|
1.5%
1/65
|
0.00%
0/66
|
|
General disorders
Chest pain
|
0.00%
0/65
|
1.5%
1/66
|
|
Injury, poisoning and procedural complications
Compression fracture
|
1.5%
1/65
|
0.00%
0/66
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/65
|
1.5%
1/66
|
|
Investigations
Ejection fraction decreased
|
3.1%
2/65
|
0.00%
0/66
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.5%
1/65
|
1.5%
1/66
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
1.5%
1/65
|
0.00%
0/66
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.5%
1/65
|
0.00%
0/66
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/65
|
1.5%
1/66
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/65
|
1.5%
1/66
|
|
Ear and labyrinth disorders
Vertigo positional
|
0.00%
0/65
|
1.5%
1/66
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/65
|
1.5%
1/66
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/65
|
1.5%
1/66
|
Other adverse events
| Measure |
Lapatinib 1500 mg QD
n=65 participants at risk
Oral lapatinib 1500 mg once daily (QD)
|
Lapatinib 500 mg BID
n=66 participants at risk
Oral lapatinib 500 mg twice daily (BID)
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
3.1%
2/65
|
6.1%
4/66
|
|
General disorders
chest discomfort
|
3.1%
2/65
|
6.1%
4/66
|
|
Gastrointestinal disorders
dyspepsia
|
1.5%
1/65
|
7.6%
5/66
|
|
Respiratory, thoracic and mediastinal disorders
dyspnoea
|
4.6%
3/65
|
4.5%
3/66
|
|
Nervous system disorders
neuropathy peripheral
|
6.2%
4/65
|
3.0%
2/66
|
|
Infections and infestations
pneumonia
|
3.1%
2/65
|
6.1%
4/66
|
|
Gastrointestinal disorders
Diarrhea
|
60.0%
39/65
|
50.0%
33/66
|
|
Skin and subcutaneous tissue disorders
Rash
|
47.7%
31/65
|
40.9%
27/66
|
|
General disorders
Fatigue
|
36.9%
24/65
|
30.3%
20/66
|
|
Gastrointestinal disorders
Nausea
|
38.5%
25/65
|
24.2%
16/66
|
|
Metabolism and nutrition disorders
Anorexia
|
26.2%
17/65
|
22.7%
15/66
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
16.9%
11/65
|
21.2%
14/66
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.8%
9/65
|
18.2%
12/66
|
|
Gastrointestinal disorders
Constipation
|
15.4%
10/65
|
16.7%
11/66
|
|
Gastrointestinal disorders
Vomiting
|
23.1%
15/65
|
9.1%
6/66
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.9%
11/65
|
13.6%
9/66
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
13.8%
9/65
|
15.2%
10/66
|
|
Nervous system disorders
Dysgeusia
|
10.8%
7/65
|
12.1%
8/66
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
9.2%
6/65
|
12.1%
8/66
|
|
Nervous system disorders
Dizziness
|
9.2%
6/65
|
10.6%
7/66
|
|
General disorders
Pyrexia
|
13.8%
9/65
|
6.1%
4/66
|
|
Gastrointestinal disorders
abdominal pain
|
9.2%
6/65
|
9.1%
6/66
|
|
Psychiatric disorders
insomnia
|
13.8%
9/65
|
4.5%
3/66
|
|
Skin and subcutaneous tissue disorders
pruritus
|
7.7%
5/65
|
10.6%
7/66
|
|
Respiratory, thoracic and mediastinal disorders
haemoptysis
|
4.6%
3/65
|
10.6%
7/66
|
|
Musculoskeletal and connective tissue disorders
musculoskeletal chest pain
|
7.7%
5/65
|
7.6%
5/66
|
|
General disorders
edema peripheral
|
7.7%
5/65
|
7.6%
5/66
|
|
General disorders
chest pain
|
6.2%
4/65
|
7.6%
5/66
|
|
Nervous system disorders
headache
|
9.2%
6/65
|
4.5%
3/66
|
|
Investigations
weight decreased
|
10.8%
7/65
|
3.0%
2/66
|
|
Skin and subcutaneous tissue disorders
alopecia
|
7.7%
5/65
|
4.5%
3/66
|
|
General disorders
asthenia
|
6.2%
4/65
|
6.1%
4/66
|
|
Skin and subcutaneous tissue disorders
dermatitis acneiform
|
6.2%
4/65
|
6.1%
4/66
|
|
Gastrointestinal disorders
flatulence
|
4.6%
3/65
|
7.6%
5/66
|
|
Musculoskeletal and connective tissue disorders
pain in extremity
|
6.2%
4/65
|
6.1%
4/66
|
|
Blood and lymphatic system disorders
anaemia
|
6.2%
4/65
|
4.5%
3/66
|
|
Psychiatric disorders
anxiety
|
7.7%
5/65
|
3.0%
2/66
|
|
General disorders
chills
|
7.7%
5/65
|
3.0%
2/66
|
|
Respiratory, thoracic and mediastinal disorders
dysphonia
|
6.2%
4/65
|
4.5%
3/66
|
|
Infections and infestations
nasopharyangitis
|
4.6%
3/65
|
6.1%
4/66
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary embolism
|
3.1%
2/65
|
7.6%
5/66
|
|
Infections and infestations
upper respiratory tract infection
|
4.6%
3/65
|
6.1%
4/66
|
|
Gastrointestinal disorders
stomatitis
|
4.6%
3/65
|
4.5%
3/66
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER