Trial Outcomes & Findings for Pemetrexed Disodium or Erlotinib Hydrochloride as Second-Line Therapy in Treating Patients With Advanced Non-small Cell Lung Cancer (NCT NCT00738881)
NCT ID: NCT00738881
Last Updated: 2015-10-29
Results Overview
Estimated using the method of Kaplan-Meier survival curves to compare PFS between the erlotinib and pemetrexed arms using an intent-to-treat (ITT) analysis. Due to the small sample size (21 of the required 954 patients \~2%), analyses within the FISH(+) and FISH(-) groups were not performed, and no formal analyses for the primary or the secondary efficacy outcomes were performed.
TERMINATED
PHASE3
23 participants
Time from randomization to the first date of documented disease progression or death, assessed up to 5 years
2015-10-29
Participant Flow
Twenty nine (29) pre-registered, screen failures (4 inadequate tissue, 1 investigator decision and one patient decision). Twenty three (23) patients were randomized, 2 patients withdrew from study prior to receiving any study treatment, thus a total of 23 randomized patients are evaluable for the primary and secondary endpoints.
Participant milestones
| Measure |
Arm I
Patients receive oral erlotinib hydrochloride once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
erlotinib hydrochloride: Given orally
|
Arm II
Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
pemetrexed disodium: Given IV
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
12
|
|
Overall Study
COMPLETED
|
11
|
10
|
|
Overall Study
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Arm I
Patients receive oral erlotinib hydrochloride once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
erlotinib hydrochloride: Given orally
|
Arm II
Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
pemetrexed disodium: Given IV
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
Baseline Characteristics
Pemetrexed Disodium or Erlotinib Hydrochloride as Second-Line Therapy in Treating Patients With Advanced Non-small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Arm I
n=11 Participants
Patients receive oral erlotinib hydrochloride once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
erlotinib hydrochloride: Given orally
|
Arm II
n=12 Participants
Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
pemetrexed disodium: Given IV
|
Total
n=23 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
69 years
n=5 Participants
|
55 years
n=7 Participants
|
62 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=5 Participants
|
12 participants
n=7 Participants
|
23 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Time from randomization to the first date of documented disease progression or death, assessed up to 5 yearsPopulation: All the 23 randomized patients are eligible for primary end point analysis using an ITT principle.
Estimated using the method of Kaplan-Meier survival curves to compare PFS between the erlotinib and pemetrexed arms using an intent-to-treat (ITT) analysis. Due to the small sample size (21 of the required 954 patients \~2%), analyses within the FISH(+) and FISH(-) groups were not performed, and no formal analyses for the primary or the secondary efficacy outcomes were performed.
Outcome measures
| Measure |
Arm I
n=11 Participants
Patients receive oral erlotinib hydrochloride once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
erlotinib hydrochloride: Given orally
|
Arm II
n=12 Participants
Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
pemetrexed disodium: Given IV
|
|---|---|---|
|
Progression-free Survival (PFS)
|
2 months
Interval 1.3 to 6.9
|
3.1 months
Interval 1.2 to 4.2
|
SECONDARY outcome
Timeframe: The time from date of randomization to the date at which the patient is removed from the treatment, assessed up to 5 yearsPopulation: Since the trial closed prematurely with only \~2% accrual, the secondary outcomes were not analyzed.
The distribution of all time to event data will be estimated using the method of Kaplan-Meier survival curves.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time from randomization to time of death from any cause, assessed up to 5 yearsPopulation: Since the trial closed prematurely with only \~2% accrual, the secondary outcomes were not analyzed.
Will be estimated using the method of Kaplan-Meier survival curves. A 1-sided stratified log rank test \[accounting for all the stratification factors except FISH status and cooperative group\] will be used to compare overall survival between the erlotinib and pemetrexed arms within the FISH(+) and FISH(-) subgroups, compare overall and progression free survival between the erlotinib and pemetrexed arms within the subgroups defined on the basis of the epidermal growth factor receptor (EGFR) expression by immunohistochemistry (IHC), and EGFR gene mutation status (MUT). Cox proportional hazards model will be used to assess potential differences.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: Since the trial closed prematurely with only \~2% accrual, the secondary outcomes were not analyzed.
Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease. The proportion of patients with confirmed CR and PR will be computed within each treatment arm and exact binomial confidence intervals for the true proportion computed. Chi-square test and Fisher's exact test will be used to compare the response rates between the treatment arms within the subgroups defined by FISH status, IHC, and MUT.
Outcome measures
Outcome data not reported
Adverse Events
Arm I
Arm II
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Arm I
n=11 participants at risk
erlotinib hydrochloride: Given orally
|
Arm II
n=10 participants at risk
pemetrexed disodium: Given IV
|
|---|---|---|
|
Blood and lymphatic system disorders
Hemoglobin decreased
|
54.5%
6/11 • Number of events 24
|
80.0%
8/10 • Number of events 30
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
|
Cardiac disorders
Myocardial ischemia
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
|
Eye disorders
Dry eye syndrome
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
|
Eye disorders
Keratitis
|
27.3%
3/11 • Number of events 4
|
0.00%
0/10
|
|
Gastrointestinal disorders
Abdominal distension
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
|
Gastrointestinal disorders
Abdominal pain
|
18.2%
2/11 • Number of events 4
|
40.0%
4/10 • Number of events 6
|
|
Gastrointestinal disorders
Constipation
|
9.1%
1/11 • Number of events 1
|
10.0%
1/10 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhea
|
81.8%
9/11 • Number of events 49
|
30.0%
3/10 • Number of events 4
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/11
|
10.0%
1/10 • Number of events 3
|
|
Gastrointestinal disorders
Ear, nose and throat examination abnormal
|
18.2%
2/11 • Number of events 2
|
10.0%
1/10 • Number of events 1
|
|
Gastrointestinal disorders
Mucositis oral
|
18.2%
2/11 • Number of events 2
|
0.00%
0/10
|
|
Gastrointestinal disorders
Nausea
|
54.5%
6/11 • Number of events 17
|
60.0%
6/10 • Number of events 15
|
|
Gastrointestinal disorders
Vomiting
|
36.4%
4/11 • Number of events 7
|
20.0%
2/10 • Number of events 4
|
|
General disorders
Chest pain
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
|
General disorders
Fatigue
|
72.7%
8/11 • Number of events 49
|
100.0%
10/10 • Number of events 38
|
|
General disorders
Fever
|
9.1%
1/11 • Number of events 1
|
40.0%
4/10 • Number of events 7
|
|
Infections and infestations
Infection
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
|
Infections and infestations
Nail infection
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
|
Infections and infestations
Pneumonia
|
9.1%
1/11 • Number of events 1
|
20.0%
2/10 • Number of events 2
|
|
Infections and infestations
Skin infection
|
9.1%
1/11 • Number of events 2
|
0.00%
0/10
|
|
Infections and infestations
Urinary tract infection
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
|
Investigations
Alanine aminotransferase increased
|
27.3%
3/11 • Number of events 13
|
20.0%
2/10 • Number of events 3
|
|
Investigations
Aspartate aminotransferase increased
|
36.4%
4/11 • Number of events 8
|
20.0%
2/10 • Number of events 3
|
|
Investigations
Bilirubin increased
|
27.3%
3/11 • Number of events 4
|
0.00%
0/10
|
|
Investigations
Creatinine increased
|
27.3%
3/11 • Number of events 4
|
20.0%
2/10 • Number of events 3
|
|
Investigations
Leukocyte count decreased
|
36.4%
4/11 • Number of events 20
|
20.0%
2/10 • Number of events 5
|
|
Investigations
Lymphocyte count decreased
|
9.1%
1/11 • Number of events 4
|
20.0%
2/10 • Number of events 3
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/11
|
20.0%
2/10 • Number of events 5
|
|
Investigations
Platelet count decreased
|
0.00%
0/11
|
30.0%
3/10 • Number of events 3
|
|
Investigations
Weight loss
|
36.4%
4/11 • Number of events 8
|
20.0%
2/10 • Number of events 4
|
|
Metabolism and nutrition disorders
Anorexia
|
63.6%
7/11 • Number of events 19
|
60.0%
6/10 • Number of events 14
|
|
Metabolism and nutrition disorders
Blood glucose increased
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
|
Metabolism and nutrition disorders
Dehydration
|
9.1%
1/11 • Number of events 2
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum albumin decreased
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum magnesium decreased
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
|
Metabolism and nutrition disorders
Serum phosphate decreased
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
|
Metabolism and nutrition disorders
Serum sodium decreased
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.1%
1/11 • Number of events 2
|
0.00%
0/10
|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Neuralgia
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
|
Nervous system disorders
Peripheral motor neuropathy
|
9.1%
1/11 • Number of events 1
|
10.0%
1/10 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
|
Psychiatric disorders
Depression
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/11
|
10.0%
1/10 • Number of events 1
|
|
Renal and urinary disorders
Hemoglobin urine positive
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
|
Renal and urinary disorders
Protein urine positive
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
36.4%
4/11 • Number of events 8
|
90.0%
9/10 • Number of events 25
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal examination abnormal
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal mucositis
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
9.1%
1/11 • Number of events 1
|
0.00%
0/10
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
81.8%
9/11 • Number of events 47
|
10.0%
1/10 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
54.5%
6/11 • Number of events 23
|
20.0%
2/10 • Number of events 3
|
|
Vascular disorders
Hypotension
|
9.1%
1/11 • Number of events 2
|
0.00%
0/10
|
Additional Information
Alex A. Adjei, M.D., Ph.D
Roswell Park Cancer Institute
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60