Trial Outcomes & Findings for Anlotinib Hydrochloride Combined With AP in Stage IIIB/IIIC/IV Non-squamous Non-small-cell Lung Cancer (NCT NCT04012619)
NCT ID: NCT04012619
Last Updated: 2023-08-03
Results Overview
The primary endpoint was the MTD of anlotinib, at which less than 33% of patients experienced a DLT in the frst treatment cycle. A DLT involving hematological toxicity was defned as grade 4 and above, non-hematological toxicity as grade 3 and above, and liver and kidney function injury as grade 2 and above.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
8 participants
Primary outcome timeframe
1 month
Results posted on
2023-08-03
Participant Flow
A standard 3+3 dose reduction design: the initial dose of anlotinib was set as 12 mg/day with a 2-week on/1-week of schedule; the dose was reduced to 10 mg/day and 8 mg/day in sequence depending on observed DLTs in cycle 1. Pemetrexed (500 mg/m2) and either cisplatin (75 mg/m2) or carboplatin (AUC=5) were intravenously given on Day 1 of each cycle.
Participant milestones
| Measure |
Anlotinib Hydrochloride (12mg) Combined With AP
Patients receive pemetrexed (500mg/m2) with cisplatin (75mg/m2)/carboplatin (area under the curve 5) once every 3 weeks, and anlotinib (12mg) once daily on days 1-14 of a 21-day cycle. Anlotinib with AP will be administrated up to 4 cycles followed by maintenance treatment with anlotinib once daily (12mg/d) on days 1-14 of a 21-day cycle until disease progression or treatment intolerance.
|
Anlotinib Hydrochloride (10mg) Combined With AP
Patients receive pemetrexed (500mg/m2) with cisplatin (75mg/m2)/carboplatin (area under the curve 5) once every 3 weeks, and anlotinib (10mg) once daily on days 1-14 of a 21-day cycle. Anlotinib with AP will be administrated up to 4 cycles followed by maintenance treatment with anlotinib once daily (10mg/d) on days 1-14 of a 21-day cycle until disease progression or treatment intolerance.
|
|---|---|---|
|
Overall Study
STARTED
|
4
|
4
|
|
Overall Study
COMPLETED
|
4
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Anlotinib Hydrochloride Combined With AP in Stage IIIB/IIIC/IV Non-squamous Non-small-cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Anlotinib Hydrochloride (12mg) Combined With AP
n=4 Participants
This dose-exploration study was a standard 3+3 dose reduction design, and eligible patients received an anlotinib chemotherapy regimen after a 21-day cycle for 4 cycles. The initial dose of anlotinib was set as 12 mg/day with a 2-week on/1-week of schedule. The dose was reduced to 10 mg/day and 8 mg/day in sequence depending on observed DLTs in cycle 1. If there were no DLTs, the dose of anlotinib in the combined chemotherapy regimen was determined to be 12 mg/day. If a DLT occurred in≥2 of 3 enrolled subjects, the initial dose was reduced to 10 mg/day. If DLT occurred in 1 of 3 subjects, the dose level was followed up, and 3 additional subjects were enrolled. If 1 DLT occurred in the last 3 subjects, the dose was reduced to 10 mg/day. Pemetrexed (500 mg/m2) and either cisplatin (75 mg/m2) or carboplatin (AUC=5) were intravenously given on Day 1 of each cycle. Patients who had disease control after the combination regimen continued to receive anlotinib maintenance until disease progression was observed.
|
Anlotinib Hydrochloride (10mg) Combined With AP
n=4 Participants
This dose-exploration study was a standard 3+3 dose reduction design, and eligible patients received an anlotinib chemotherapy regimen after a 21-day cycle for 4 cycles. The initial dose of anlotinib was set as 12 mg/day with a 2-week on/1-week of schedule. The dose was reduced to 10 mg/day and 8 mg/day in sequence depending on observed DLTs in cycle 1. If there were no DLTs, the dose of anlotinib in the combined chemotherapy regimen was determined to be 12 mg/day. If a DLT occurred in≥2 of 3 enrolled subjects, the initial dose was reduced to 10 mg/day. If DLT occurred in 1 of 3 subjects, the dose level was followed up, and 3 additional subjects were enrolled. If 1 DLT occurred in the last 3 subjects, the dose was reduced to 10 mg/day. Pemetrexed (500 mg/m2) and either cisplatin (75 mg/m2) or carboplatin (AUC=5) were intravenously given on Day 1 of each cycle. Patients who had disease control after the combination regimen continued to receive anlotinib maintenance until disease progression was observed.
|
Total
n=8 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
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Continuous
|
61 years
n=5 Participants
|
66 years
n=7 Participants
|
62 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 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
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 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
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Smoking history
Ever
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Smoking history
Never
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 monthThe primary endpoint was the MTD of anlotinib, at which less than 33% of patients experienced a DLT in the frst treatment cycle. A DLT involving hematological toxicity was defned as grade 4 and above, non-hematological toxicity as grade 3 and above, and liver and kidney function injury as grade 2 and above.
Outcome measures
| Measure |
Anlotinib Hydrochloride Combined With AP
n=8 Participants
Patients receive pemetrexed (500mg/m2) with cisplatin (75mg/m2)/carboplatin (area under the curve 5) once every 3 weeks, and anlotinib (dose escalation) once daily on days 1-14 of a 21-day cycle. Anlotinib with AP will be administrated up to 4 cycles followed by maintenance treatment with anlotinib once daily (12mg/d) on days 1-14 of a 21-day cycle until disease progression or treatment intolerance.
Anlotinib Hydrochloride: Patients receive pemetrexed with cisplatin/carboplatin once every 3 weeks, and anlotinib (dose escalation) once daily on days 1-14.
|
|---|---|
|
the Maximum Tolerated Dose (MTD)
|
10 mg
|
Adverse Events
Anlotinib Hydrochloride (12mg) Combined With AP
Serious events: 2 serious events
Other events: 4 other events
Deaths: 0 deaths
Anlotinib Hydrochloride (10mg) Combined With AP
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Anlotinib Hydrochloride (12mg) Combined With AP
n=4 participants at risk
Patients receive pemetrexed (500mg/m2) with cisplatin (75mg/m2)/carboplatin (area under the curve 5) once every 3 weeks, and anlotinib (12mg) once daily on days 1-14 of a 21-day cycle. Anlotinib with AP will be administrated up to 4 cycles followed by maintenance treatment with anlotinib once daily (12mg/d) on days 1-14 of a 21-day cycle until disease progression or treatment intolerance.
|
Anlotinib Hydrochloride (10mg) Combined With AP
n=4 participants at risk
Patients receive pemetrexed (500mg/m2) with cisplatin (75mg/m2)/carboplatin (area under the curve 5) once every 3 weeks, and anlotinib (10mg) once daily on days 1-14 of a 21-day cycle. Anlotinib with AP will be administrated up to 4 cycles followed by maintenance treatment with anlotinib once daily (10mg/d) on days 1-14 of a 21-day cycle until disease progression or treatment intolerance.
|
|---|---|---|
|
Metabolism and nutrition disorders
appetite loss
|
25.0%
1/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
0.00%
0/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
|
Musculoskeletal and connective tissue disorders
hand-foot syndrome
|
25.0%
1/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
0.00%
0/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
Other adverse events
| Measure |
Anlotinib Hydrochloride (12mg) Combined With AP
n=4 participants at risk
Patients receive pemetrexed (500mg/m2) with cisplatin (75mg/m2)/carboplatin (area under the curve 5) once every 3 weeks, and anlotinib (12mg) once daily on days 1-14 of a 21-day cycle. Anlotinib with AP will be administrated up to 4 cycles followed by maintenance treatment with anlotinib once daily (12mg/d) on days 1-14 of a 21-day cycle until disease progression or treatment intolerance.
|
Anlotinib Hydrochloride (10mg) Combined With AP
n=4 participants at risk
Patients receive pemetrexed (500mg/m2) with cisplatin (75mg/m2)/carboplatin (area under the curve 5) once every 3 weeks, and anlotinib (10mg) once daily on days 1-14 of a 21-day cycle. Anlotinib with AP will be administrated up to 4 cycles followed by maintenance treatment with anlotinib once daily (10mg/d) on days 1-14 of a 21-day cycle until disease progression or treatment intolerance.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Hand-foot syndrome
|
50.0%
2/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
0.00%
0/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
|
Gastrointestinal disorders
Diarrhea
|
50.0%
2/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
0.00%
0/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
|
Gastrointestinal disorders
Proteinuria
|
25.0%
1/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
25.0%
1/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
|
Cardiac disorders
Hypertension
|
75.0%
3/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
25.0%
1/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
|
Metabolism and nutrition disorders
Vomiting
|
50.0%
2/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
0.00%
0/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
75.0%
3/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
50.0%
2/4 • 12 months
Adverse events (AEs) were monitored during the study and summarized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place