Trial Outcomes & Findings for Abraxane and Alimta in Advanced Solid Tumors (NCT NCT00470548)
NCT ID: NCT00470548
Last Updated: 2018-01-10
Results Overview
Dose limiting toxicity (DLT) was defined as any of the following occurring during the first cycle: Grade 4 thrombocytopenia, or grade 3 thrombocytopenia associated with bleeding, requirement for transfusion, febrile neutropenia, neutropenia with documented infection. Non-hematologic DLT included any other ≥ grade 3 non-hematologic toxicity that was clinically significant and considered by the investigator to be related to study drug. Alopecia and grade 3 allergic reaction/hypersensitivity with infusion were not considered DLTs.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
49 participants
Primary outcome timeframe
Up to21 days
Results posted on
2018-01-10
Participant Flow
Participant milestones
| Measure |
Phase I: Dose Level 1
Pemetrexed 500 mg/m2 plus Abraxane 180 mg/m2
|
Phase I: Dose Level 2
Pemetrexed 500 mg/m2 plus Abraxane 220 mg/m2
|
Phase I: Dose Level 3
Pemetrexed 500 mg/m2 plus Abraxane 260 mg/m2
|
Phase II
Pemetrexed 500 mg/m2 plus Abraxane 260 mg/m2
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
6
|
37
|
|
Overall Study
COMPLETED
|
3
|
3
|
6
|
37
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Abraxane and Alimta in Advanced Solid Tumors
Baseline characteristics by cohort
| Measure |
Phase I: Abraxane and Pemetrexed
n=12 Participants
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 180 mg/m2, 220 mg/m2 and 260 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
Phase II: Abraxane and Pemetrexed
n=37 Participants
Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 260 mg/m2IV administration following pemetrexed on Day 1 of each cycle
|
Total
n=49 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
70 years
n=99 Participants
|
63 years
n=107 Participants
|
63 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
19 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
30 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
12 Participants
n=99 Participants
|
37 Participants
n=107 Participants
|
49 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Up to21 daysPopulation: At dose level 1, 2 and 3 three participants were treated with no dose limiting toxicities. Three additional participants were treated at dose level 3 with no dose limiting toxicities.
Dose limiting toxicity (DLT) was defined as any of the following occurring during the first cycle: Grade 4 thrombocytopenia, or grade 3 thrombocytopenia associated with bleeding, requirement for transfusion, febrile neutropenia, neutropenia with documented infection. Non-hematologic DLT included any other ≥ grade 3 non-hematologic toxicity that was clinically significant and considered by the investigator to be related to study drug. Alopecia and grade 3 allergic reaction/hypersensitivity with infusion were not considered DLTs.
Outcome measures
| Measure |
Phase I: Dose Level 1
n=3 Participants
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 180 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
Phase I: Dose Level 2
n=3 Participants
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 220 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
Phase I: Dose Level 3
n=6 Participants
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 260 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
|---|---|---|---|
|
Number of Participants With Dose Limiting Toxicities
|
0 participants
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Up to 1 yearToxicities was evaluated based on the standard NCI CTCAE Version 3.0 grading criteria. Attributable grade ≥ 3 hematologic and non-hematologic toxicities are presented here.
Outcome measures
| Measure |
Phase I: Dose Level 1
n=37 Participants
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 180 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
Phase I: Dose Level 2
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 220 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
Phase I: Dose Level 3
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 260 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
|---|---|---|---|
|
Number of Patients With Toxicities
|
15 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Of the 12 patients in the phase I component 10 were assessable for response. In the phase II component, 31 of 37 patients were evaluable for response.
From time of enrollment to the first observation of disease progression or death.
Outcome measures
| Measure |
Phase I: Dose Level 1
n=10 Participants
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 180 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
Phase I: Dose Level 2
n=31 Participants
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 220 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
Phase I: Dose Level 3
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 260 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
|---|---|---|---|
|
Duration of Overall Survival
|
13.5 months
Standard Error 0
|
4.5 months
Standard Error 0
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsPer RECIST criteria, complete response (CR) is defined as the disappearance of all target lesions.
Outcome measures
| Measure |
Phase I: Dose Level 1
n=12 Participants
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 180 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
Phase I: Dose Level 2
n=37 Participants
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 220 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
Phase I: Dose Level 3
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 260 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
|---|---|---|---|
|
Number of Participants With Complete Response
|
0 participants
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsStable Disease is measured from the start of the treatment until the criteria for disease progression are met. 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 |
Phase I: Dose Level 1
n=12 Participants
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 180 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
Phase I: Dose Level 2
n=37 Participants
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 220 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
Phase I: Dose Level 3
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 260 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
|---|---|---|---|
|
Number of Participants With Stable Disease
|
7 Participants
|
12 Participants
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsAt least a 30% decrease in the sum of the longest diameter of target lesions
Outcome measures
| Measure |
Phase I: Dose Level 1
n=12 Participants
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 180 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
Phase I: Dose Level 2
n=37 Participants
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 220 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
Phase I: Dose Level 3
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 260 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
|---|---|---|---|
|
Number of Participants With Partial Response
|
0 Participants
|
5 Participants
|
—
|
SECONDARY outcome
Timeframe: Up to 2 yearsDisease control is complete response plus partial response plus stable disease from the start of treatment to death or disease progression.
Outcome measures
| Measure |
Phase I: Dose Level 1
n=12 Participants
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 180 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
Phase I: Dose Level 2
n=37 Participants
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 220 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
Phase I: Dose Level 3
A 3 + 3 dose escalation design was used to determine the maximum tolerated dose and the recommended phase II dose. Alimta® (pemetrexed) 500 mg/m2 IV administration on Day 1 of each cycle with Abraxane® (ABI 007) 260 mg/m2 IV administration following pemetrexed on Day 1 of each cycle .
|
|---|---|---|---|
|
Number of Participants With Disease Control
|
7 Participants
|
17 Participants
|
—
|
Adverse Events
Phase I: Abraxane and Alimta
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Phase II: Abraxane and Alimta
Serious events: 6 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase I: Abraxane and Alimta
n=12 participants at risk
Three dose levels were tested. Pemetrexed 500mg/m2 day 1 and nab-paclitaxel day 1 at 180, 220, and 260 mg/m2 every 21 days.
Abraxane: ABI-007 IV administration following pemetrexed on Day 1 of each cycle (infused over 30 minutes)
Alimta: Pemetrexed IV administration on Day 1 of each cycle (infused over 10 minutes)
|
Phase II: Abraxane and Alimta
n=37 participants at risk
Pemetrexed 500mg/m2 day 1 and nab-paclitaxel day 1 at 260 mg/m2 every 21 days.
Abraxane: ABI-007 IV administration following pemetrexed on Day 1 of each cycle (infused over 30 minutes)
Alimta: Pemetrexed IV administration on Day 1 of each cycle (infused over 10 minutes)
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
8.3%
1/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
0.00%
0/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
5.4%
2/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
General disorders
Fever
|
0.00%
0/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
2.7%
1/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
Cardiac disorders
Cardiac Ischemia
|
0.00%
0/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
2.7%
1/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
Blood and lymphatic system disorders
Nasal Hemorrhage
|
0.00%
0/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
2.7%
1/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
2.7%
1/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
Infections and infestations
Skin Infection
|
0.00%
0/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
2.7%
1/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
Blood and lymphatic system disorders
Hemoglobin
|
0.00%
0/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
2.7%
1/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
Other adverse events
| Measure |
Phase I: Abraxane and Alimta
n=12 participants at risk
Three dose levels were tested. Pemetrexed 500mg/m2 day 1 and nab-paclitaxel day 1 at 180, 220, and 260 mg/m2 every 21 days.
Abraxane: ABI-007 IV administration following pemetrexed on Day 1 of each cycle (infused over 30 minutes)
Alimta: Pemetrexed IV administration on Day 1 of each cycle (infused over 10 minutes)
|
Phase II: Abraxane and Alimta
n=37 participants at risk
Pemetrexed 500mg/m2 day 1 and nab-paclitaxel day 1 at 260 mg/m2 every 21 days.
Abraxane: ABI-007 IV administration following pemetrexed on Day 1 of each cycle (infused over 30 minutes)
Alimta: Pemetrexed IV administration on Day 1 of each cycle (infused over 10 minutes)
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
16.7%
2/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
5.4%
2/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
Blood and lymphatic system disorders
Leukopenia
|
8.3%
1/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
5.4%
2/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
5.4%
2/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
Blood and lymphatic system disorders
Neutropenia
|
16.7%
2/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
8.1%
3/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
Cardiac disorders
Cardiac Ischemia
|
0.00%
0/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
2.7%
1/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
Skin and subcutaneous tissue disorders
Cellulitis
|
0.00%
0/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
2.7%
1/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
General disorders
Fatigue
|
8.3%
1/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
0.00%
0/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
General disorders
Hypersensitivity
|
0.00%
0/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
2.7%
1/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
Blood and lymphatic system disorders
Hypoalbuminemia
|
8.3%
1/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
2.7%
1/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
Blood and lymphatic system disorders
Increased transaminases
|
0.00%
0/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
2.7%
1/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
Nervous system disorders
Sensory neuropathy
|
8.3%
1/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
0.00%
0/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/12 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
2.7%
1/37 • Up to 1 year
Adverse events until they are resolved or stabilized, the patient is lost to follow-up, or the event is otherwise explained.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place