Trial Outcomes & Findings for Dose Escalating Study of the Safety and Efficacy of Patupilone, q3w, in Patients With Non-small Cell Lung Cancer (NCT NCT00171834)
NCT ID: NCT00171834
Last Updated: 2014-02-05
Results Overview
The MTD was defined as the highest dose of patupilone administered every three weeks (q3w) where not more than one out of six patients experienced a DLT using a standard 3+3 design. Dose escalation started at 6.5 mg/m\^2 until MTD in steps of 0.5 mg/m\^2 until 12 mg/m\^2, then in steps of 1 mg/m\^2 till 13.0 mg/m\^2. DLTs were assessed during cycle 1. During this time frame, no more than one DLT occurred in any of the explored dose levels up to 13 mg/m\^2, thus, the MTD as defined by the protocol was not reached in this study.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
89 participants
Primary outcome timeframe
Cycle 1 (21 days)
Results posted on
2014-02-05
Participant Flow
Participant milestones
| Measure |
Patupilone ≤7.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 7.5-8.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 8.5-9.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0-11.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0-13.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10 mg/m^2 (Phase II) NSCLC Cohort
Patupilone was administered as a single i.v. infusion over 20 minutes (Amendment 4), once every 3 weeks.
|
Patupilone 10 mg/m^2 (Phase II) NSCLC w.BM Cohort
Patupilone was administered as a single i.v. infusion over 20 minutes (Amendment 4), once every 3 weeks.
|
|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
6
|
12
|
12
|
12
|
8
|
35
|
4
|
|
Overall Study
Completed 6 Cycles of Treatment
|
0
|
0
|
1
|
0
|
2
|
1
|
0
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
6
|
12
|
12
|
12
|
8
|
35
|
4
|
Reasons for withdrawal
| Measure |
Patupilone ≤7.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 7.5-8.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 8.5-9.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0-11.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0-13.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10 mg/m^2 (Phase II) NSCLC Cohort
Patupilone was administered as a single i.v. infusion over 20 minutes (Amendment 4), once every 3 weeks.
|
Patupilone 10 mg/m^2 (Phase II) NSCLC w.BM Cohort
Patupilone was administered as a single i.v. infusion over 20 minutes (Amendment 4), once every 3 weeks.
|
|---|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
2
|
1
|
3
|
2
|
2
|
15
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
0
|
1
|
1
|
1
|
0
|
|
Overall Study
Death from study indication
|
0
|
1
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Disease Progression
|
4
|
8
|
8
|
9
|
2
|
18
|
3
|
|
Overall Study
Treatment Duration Completed
|
0
|
0
|
1
|
0
|
2
|
1
|
0
|
Baseline Characteristics
Dose Escalating Study of the Safety and Efficacy of Patupilone, q3w, in Patients With Non-small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Patupilone ≤7.0 mg/m^2 (Phase I)
n=6 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 7.5-8.0 mg/m^2 (Phase I)
n=12 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 8.5-9.5 mg/m^2 (Phase I)
n=12 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0-11.5 mg/m^2 (Phase I)
n=12 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0-13.0 mg/m^2 (Phase I)
n=8 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10 mg/m^2 (Phase II) NSCLC Cohort
n=35 Participants
Patupilone was administered as a single i.v. infusion over 20 minutes (Amendment 4), once every 3 weeks.
|
Patupilone 10 mg/m^2 (Phase II) NSCLC w.BM Cohort
n=4 Participants
Patupilone was administered as a single i.v. infusion over 20 minutes (Amendment 4), once every 3 weeks.
|
Total
n=89 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
58.3 years
STANDARD_DEVIATION 12.01 • n=5 Participants
|
59.4 years
STANDARD_DEVIATION 8.98 • n=7 Participants
|
57.8 years
STANDARD_DEVIATION 9.31 • n=5 Participants
|
57.6 years
STANDARD_DEVIATION 9.07 • n=4 Participants
|
56.3 years
STANDARD_DEVIATION 13.31 • n=21 Participants
|
63.3 years
STANDARD_DEVIATION 8.04 • n=8 Participants
|
60.5 years
STANDARD_DEVIATION 9.71 • n=8 Participants
|
57.9 years
STANDARD_DEVIATION 9.85 • n=24 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
10 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
30 Participants
n=24 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
25 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
59 Participants
n=24 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
6 participants
n=5 Participants
|
12 participants
n=7 Participants
|
11 participants
n=5 Participants
|
12 participants
n=4 Participants
|
8 participants
n=21 Participants
|
35 participants
n=8 Participants
|
4 participants
n=8 Participants
|
88 participants
n=24 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
0 participants
n=8 Participants
|
0 participants
n=8 Participants
|
1 participants
n=24 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 (21 days)Population: Maximum tolerated dose (MTD) determining population.included all patients who completed the first treatment cycle (Cycle 1) according to protocol or discontinued due to a DLT. The first cycle data from this patient population were used to determine the MTD in the Phase I part of the study.
The MTD was defined as the highest dose of patupilone administered every three weeks (q3w) where not more than one out of six patients experienced a DLT using a standard 3+3 design. Dose escalation started at 6.5 mg/m\^2 until MTD in steps of 0.5 mg/m\^2 until 12 mg/m\^2, then in steps of 1 mg/m\^2 till 13.0 mg/m\^2. DLTs were assessed during cycle 1. During this time frame, no more than one DLT occurred in any of the explored dose levels up to 13 mg/m\^2, thus, the MTD as defined by the protocol was not reached in this study.
Outcome measures
| Measure |
Patupilone ≤7.0 mg/m^2 (Phase I)
n=3 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 7.5-8.0 mg/m^2 (Phase I)
n=3 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 8.5-9.5 mg/m^2 (Phase I)
n=6 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0-11.5 mg/m^2 (Phase I)
n=6 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0-13.0 mg/m^2 (Phase I)
n=6 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.0 mg/m^2 (Phase I)
n=3 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.5 mg/m^2 (Phase I)
n=3 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0 mg/m^2 (Phase I)
n=3 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.5 mg/m^2 (Phase I)
n=3 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.0 mg/m^2 (Phase I)
n=3 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.5 mg/m^2 (Phase I)
n=3 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0 mg/m^2 (Phase I)
n=3 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 13.0 mg/m^2 (Phase I)
n=5 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Phase I: Number of Total Dose-limiting Toxicity (DLT) During Dose Escalation to Determine Maximum Tolerated Dose (MTD)
Asthenia
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
1 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
|
Phase I: Number of Total Dose-limiting Toxicity (DLT) During Dose Escalation to Determine Maximum Tolerated Dose (MTD)
Diarrhea
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
1 Dose Limiting Toxicity (DLT)
|
1 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
1 Dose Limiting Toxicity (DLT)
|
|
Phase I: Number of Total Dose-limiting Toxicity (DLT) During Dose Escalation to Determine Maximum Tolerated Dose (MTD)
Any DLT
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
1 Dose Limiting Toxicity (DLT)
|
1 Dose Limiting Toxicity (DLT)
|
1 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
0 Dose Limiting Toxicity (DLT)
|
1 Dose Limiting Toxicity (DLT)
|
PRIMARY outcome
Timeframe: At baseline, then every second cycle (approximately every 6 weeks), until disease progression or discontinuation. Average 18 weeks.Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of patupilone. Analysis of the primary and all secondary efficacy endpoints was performed based on this population. According to the Intention to Treat (ITT) principle, patients were analyzed based on the treatment to which they were assigned at study entry.
Overall response is the number of participants who had a complete response (CR) or a partial response (PR) based on local investigator's assessment of RECIST criteria. Per RECIST: CR, all detectable tumor has disappeared; PR, a \>=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the baseline sum, no worsening of non-TLs, and no new lesions; Progressive disease (PD), a \>=20% increase in TLs, clearly worsening of non-TLs, or emergence of new lesions; Stable Disease (SD), small changes that do not meet previously given criteria.
Outcome measures
| Measure |
Patupilone ≤7.0 mg/m^2 (Phase I)
n=35 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 7.5-8.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 8.5-9.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0-11.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0-13.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 13.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Phase II: Number of Participants With Best Overall Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST)
Partial Response (PR)
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Phase II: Number of Participants With Best Overall Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST)
Stable Disease (SD)
|
9 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Phase II: Number of Participants With Best Overall Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST)
Progressive Disease (PD)
|
13 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Phase II: Number of Participants With Best Overall Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST)
Unknown
|
7 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Phase II: Number of Participants With Best Overall Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST)
Complete Response
|
0 Participants
Interval 6.596 to 30.55
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Phase II: Number of Participants With Best Overall Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST)
Best overall response (CR, PR) & the response rate
|
6 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Best achieved overall response according to RECIST from start of study until study discontinuation. Imaging was assessed every second cycle (ie. approximately every 6 weeks) until disease progression or discontinuation. Average 18 weeksPopulation: Full Analysis Set (FAS) consisted of all patients who received at least one dose of patupilone. Analysis of the primary and all secondary efficacy endpoints was performed based on this population. According to the Intention to Treat (ITT) principle, patients were analyzed based on the treatment to which they were assigned at study entry.
This was defined as the number of participants whose best overall response was CR or PR by RECIST. Per RECIST: CR, all detectable tumor has disappeared; PR, a \>=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the baseline sum, no worsening of non-TLs, and no new lesions; Progressive disease (PD), a \>=20% increase in TLs, clearly worsening of non-TLs, or emergence of new lesions; Stable Disease (SD), small changes that do not meet previously given criteria.
Outcome measures
| Measure |
Patupilone ≤7.0 mg/m^2 (Phase I)
n=6 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 7.5-8.0 mg/m^2 (Phase I)
n=12 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 8.5-9.5 mg/m^2 (Phase I)
n=12 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0-11.5 mg/m^2 (Phase I)
n=12 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0-13.0 mg/m^2 (Phase I)
n=8 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 13.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Best Overall Response-Phase I
Complete Response (CR)
|
0 Participants
0
|
0 Participants
0
|
0 Participants
0
|
0 Participants
0
|
0 Participants
0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Best Overall Response-Phase I
Stable Disease (SD)
|
1 Participants
16.7
|
2 Participants
16.7
|
5 Participants
41.7
|
4 Participants
33.3
|
5 Participants
62.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Best Overall Response-Phase I
Unknown
|
0 Participants
0
|
3 Participants
25.0
|
1 Participants
8.3
|
1 Participants
8.3
|
2 Participants
25.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Best Overall Response-Phase I
Best overall response (CR,PR) & the response rate
|
0 Participants
0
|
3 Participants
25.0
|
1 Participants
8.3
|
1 Participants
8.3
|
0 Participants
0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Best Overall Response-Phase I
Partial Response (PR)
|
0 Participants
0
|
3 Participants
25
|
1 Participants
8.3
|
1 Participants
8.3
|
0 Participants
0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Best Overall Response-Phase I
Progressive Disease (PD)
|
5 Participants
83.3
|
4 Participants
33.3
|
5 Participants
41.7
|
6 Participants
50.0
|
1 Participants
12.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From start of study drug to date of death due to any cause. Follow-up after treatment discontinuation approximately every 3 months until approximately 70% of participants have reached the survival endpoint. Average 9.75 monthsPopulation: Full Analysis Set (FAS) consisted of all patients who received at least one dose of patupilone. Analysis of the primary and all secondary efficacy endpoints was performed based on this population. According to the Intention to Treat (ITT) principle, patients were analyzed based on the treatment to which they were assigned at study entry.
Overall survival (OS) time was measured from the start of study drug to the date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last contact. Data was collected post treatment every 3 months until approximately 70% of patients have reached the survival endpoint (Phase I + Phase II).
Outcome measures
| Measure |
Patupilone ≤7.0 mg/m^2 (Phase I)
n=50 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 7.5-8.0 mg/m^2 (Phase I)
n=35 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 8.5-9.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0-11.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0-13.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 13.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Overall Survival Time-Phase I and Phase II
|
9.2 Months
Interval 6.8 to 12.9
|
10.3 Months
Interval 6.0 to 13.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline, then every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from study. Average 18 weeksPopulation: Full Analysis Set (FAS) consisted of all patients who received at least one dose of patupilone. Analysis of the primary and all secondary efficacy endpoints was performed based on this population. According to the Intention to Treat (ITT) principle, patients were analyzed based on the treatment to which they were assigned at study entry.
Time to progression was measured from the start of study drug to the date of first documented disease progression by RECIST, discontinuation due to disease progression, or death from underlying cancer, whichever event occurred first. If a patient had not progressed by RECIST, discontinued due to disease progression, or died from underlying cancer, TTP was censored at the time of last adequate tumor assessment. However, if a patient took any new cancer therapy prior to PD or death, then TTP was censored at the date of last adequate tumor assessment prior to the start date of new cancer therapy.
Outcome measures
| Measure |
Patupilone ≤7.0 mg/m^2 (Phase I)
n=50 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 7.5-8.0 mg/m^2 (Phase I)
n=35 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 8.5-9.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0-11.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0-13.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 13.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Time to Progression (TTP)-Phase I and Phase II
|
2.1 Months
Interval 0.8 to 3.5
|
2.1 Months
Interval 1.9 to 3.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Imaging was assessed every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from treatment . Average 18 weeksPopulation: Full Analysis Set (FAS) consisted of all patients who received at least one dose of patupilone. Analysis of the primary and all secondary efficacy endpoints was performed based on this population. According to the Intention to Treat (ITT) principle, patients were analyzed based on the treatment to which they were assigned at study entry.
Duration of stable disease (CR, PR, or SD) by RECIST was defined as the time from start of study drug to the date of first documented disease progression or discontinuation due to disease progression, or death from underlying cancer, whichever event occured first.
Outcome measures
| Measure |
Patupilone ≤7.0 mg/m^2 (Phase I)
n=50 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 7.5-8.0 mg/m^2 (Phase I)
n=35 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 8.5-9.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0-11.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0-13.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 13.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Duration of Stable Disease-Phase I and Phase II
|
3.7 Months
Interval 3.5 to 4.9
|
5.6 Months
Interval 3.5 to 9.0
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline, then every second cycle (i.e. approximately every 6 weeks), until disease progression or discontinuation from study. Average 18 weeksPopulation: Full Analysis Set (FAS) consisted of all patients who received at least one dose of patupilone. Analysis of the primary and all secondary efficacy endpoints was performed based on this population. According to the Intention to Treat (ITT) principle, patients were analyzed based on the treatment to which they were assigned at study entry.
Time to overall response (CR or PR) measured by RECIST was the time between study start until date of first documented response (CR or PR).
Outcome measures
| Measure |
Patupilone ≤7.0 mg/m^2 (Phase I)
n=50 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 7.5-8.0 mg/m^2 (Phase I)
n=35 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 8.5-9.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0-11.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0-13.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 13.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Time to Overall Response -Phase I and Phase II
|
2.6 Months
Interval 1.2 to 3.5
|
3.4 Months
Interval 1.0 to 6.5
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Duration of response according to RECIST from start of study until study discontinuation. Duration of response was assessed every second cycle ( i.e. approximately every 6 weeks) until disease progression or discontinuation from study. Average 18 weeksPopulation: Full Analysis Set (FAS) consisted of all patients who received at least one dose of patupilone. Analysis of the primary and all secondary efficacy endpoints was performed based on this population. According to the Intention to Treat (ITT) principle, patients were analyzed based on the treatment to which they were assigned at study entry.
Duration of overall response (CR or PR) measured by RECIST was measured from the first documented CR or PR to the date of first documented disease progression or discontinuation due to disease progression, or death from underlying cancer, whichever event occured first.
Outcome measures
| Measure |
Patupilone ≤7.0 mg/m^2 (Phase I)
n=50 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 7.5-8.0 mg/m^2 (Phase I)
n=35 Participants
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 8.5-9.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0-11.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0-13.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 9.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 11.5 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 13.0 mg/m^2 (Phase I)
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Duration of Overall Response -Phase I and Phase II
|
2.6 Months
Interval 2.3 to 2.6
|
NA Months
Interval 2.5 to
Median duration was not calculated due to small number of participants (4). Outer bound of the 95% CI was not attained
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Patupilone ≤7.0 mg/m^2 (Phase I)
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Patupilone 7.5-8.0 mg/m^2 (Phase I)
Serious events: 3 serious events
Other events: 11 other events
Deaths: 0 deaths
Patupilone 8.5-9.5 mg/m^2 (Phase I)
Serious events: 2 serious events
Other events: 12 other events
Deaths: 0 deaths
Patupilone 10.0-11.5 mg/m^2 (Phase I)
Serious events: 3 serious events
Other events: 10 other events
Deaths: 0 deaths
Patupilone 12.0-13.0 mg/m^2 (Phase I)
Serious events: 4 serious events
Other events: 8 other events
Deaths: 0 deaths
Patupilone 10 mg/m^2 (Phase II) NSCLC Cohort
Serious events: 14 serious events
Other events: 33 other events
Deaths: 0 deaths
Patupilone 10 mg/m^2 (Phase II) NSCLC w. Brain Metastases (BM)
Serious events: 2 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Patupilone ≤7.0 mg/m^2 (Phase I)
n=6 participants at risk
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 7.5-8.0 mg/m^2 (Phase I)
n=12 participants at risk
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 8.5-9.5 mg/m^2 (Phase I)
n=12 participants at risk
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0-11.5 mg/m^2 (Phase I)
n=12 participants at risk
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0-13.0 mg/m^2 (Phase I)
n=8 participants at risk
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10 mg/m^2 (Phase II) NSCLC Cohort
n=35 participants at risk
Patupilone was administered as a single i.v. infusion over 20 minutes (Amendment 4), once every 3 weeks.
|
Patupilone 10 mg/m^2 (Phase II) NSCLC w. Brain Metastases (BM)
n=4 participants at risk
Patupilone was administered as a single i.v. infusion over 20 minutes (Amendment 4), once every 3 weeks.
|
|---|---|---|---|---|---|---|---|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Diarrhoea
|
16.7%
1/6
|
8.3%
1/12
|
8.3%
1/12
|
8.3%
1/12
|
12.5%
1/8
|
22.9%
8/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
25.0%
1/4
|
|
General disorders
Asthenia
|
16.7%
1/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
12.5%
1/8
|
2.9%
1/35
|
0.00%
0/4
|
|
General disorders
Fatigue
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
25.0%
1/4
|
|
General disorders
Oedema peripheral
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
25.0%
1/4
|
|
Infections and infestations
Escherichia infection
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Infections and infestations
Pneumonia
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
8.3%
1/12
|
0.00%
0/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Infections and infestations
Pseudomonas infection
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Infections and infestations
Urinary tract infection
|
16.7%
1/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
25.0%
1/4
|
|
Nervous system disorders
Paraparesis
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Nervous system disorders
Peripheral sensorimotor neuropathy
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
25.0%
1/4
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
12.5%
1/8
|
2.9%
1/35
|
0.00%
0/4
|
Other adverse events
| Measure |
Patupilone ≤7.0 mg/m^2 (Phase I)
n=6 participants at risk
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 7.5-8.0 mg/m^2 (Phase I)
n=12 participants at risk
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 8.5-9.5 mg/m^2 (Phase I)
n=12 participants at risk
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10.0-11.5 mg/m^2 (Phase I)
n=12 participants at risk
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 12.0-13.0 mg/m^2 (Phase I)
n=8 participants at risk
Patupilone was administered as a single i.v. infusion over 5 to 10 minutes (Amendment 1) until (Amendment 2) and over 10 to 20 minutes (Amendment 2) until the completion of Phase I part of the study.
|
Patupilone 10 mg/m^2 (Phase II) NSCLC Cohort
n=35 participants at risk
Patupilone was administered as a single i.v. infusion over 20 minutes (Amendment 4), once every 3 weeks.
|
Patupilone 10 mg/m^2 (Phase II) NSCLC w. Brain Metastases (BM)
n=4 participants at risk
Patupilone was administered as a single i.v. infusion over 20 minutes (Amendment 4), once every 3 weeks.
|
|---|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
50.0%
3/6
|
50.0%
6/12
|
75.0%
9/12
|
58.3%
7/12
|
87.5%
7/8
|
82.9%
29/35
|
100.0%
4/4
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
25.0%
2/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Faecal incontinence
|
16.7%
1/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
25.0%
3/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Nausea
|
50.0%
3/6
|
25.0%
3/12
|
33.3%
4/12
|
41.7%
5/12
|
37.5%
3/8
|
17.1%
6/35
|
25.0%
1/4
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
8.3%
1/12
|
12.5%
1/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Tooth loss
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Vomiting
|
16.7%
1/6
|
33.3%
4/12
|
41.7%
5/12
|
25.0%
3/12
|
37.5%
3/8
|
34.3%
12/35
|
25.0%
1/4
|
|
General disorders
Asthenia
|
16.7%
1/6
|
16.7%
2/12
|
25.0%
3/12
|
0.00%
0/12
|
12.5%
1/8
|
31.4%
11/35
|
0.00%
0/4
|
|
General disorders
Axillary pain
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
General disorders
Chest pain
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/35
|
0.00%
0/4
|
|
General disorders
Chills
|
0.00%
0/6
|
8.3%
1/12
|
16.7%
2/12
|
25.0%
3/12
|
37.5%
3/8
|
8.6%
3/35
|
0.00%
0/4
|
|
General disorders
Face oedema
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
General disorders
Fatigue
|
50.0%
3/6
|
16.7%
2/12
|
33.3%
4/12
|
25.0%
3/12
|
37.5%
3/8
|
14.3%
5/35
|
25.0%
1/4
|
|
General disorders
Feeling hot
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
General disorders
Localised oedema
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
General disorders
Oedema peripheral
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/8
|
2.9%
1/35
|
25.0%
1/4
|
|
General disorders
Pyrexia
|
0.00%
0/6
|
25.0%
3/12
|
25.0%
3/12
|
8.3%
1/12
|
25.0%
2/8
|
11.4%
4/35
|
0.00%
0/4
|
|
General disorders
Temperature intolerance
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
25.0%
1/4
|
|
Immune system disorders
Hypersensitivity
|
16.7%
1/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Infections and infestations
Bronchitis
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/8
|
5.7%
2/35
|
0.00%
0/4
|
|
Infections and infestations
Influenza
|
16.7%
1/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Infections and infestations
Pneumonia
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
12.5%
1/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
25.0%
1/4
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
5.7%
2/35
|
0.00%
0/4
|
|
Investigations
Blood magnesium decreased
|
16.7%
1/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
14.3%
5/35
|
0.00%
0/4
|
|
Investigations
Weight decreased
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
8.3%
1/12
|
12.5%
1/8
|
22.9%
8/35
|
25.0%
1/4
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/6
|
25.0%
3/12
|
8.3%
1/12
|
0.00%
0/12
|
50.0%
4/8
|
34.3%
12/35
|
0.00%
0/4
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/6
|
8.3%
1/12
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/8
|
14.3%
5/35
|
0.00%
0/4
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
5.7%
2/35
|
0.00%
0/4
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
12.5%
1/8
|
5.7%
2/35
|
0.00%
0/4
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
25.0%
1/4
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
1/6
|
0.00%
0/12
|
16.7%
2/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/6
|
8.3%
1/12
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/8
|
8.6%
3/35
|
0.00%
0/4
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
16.7%
1/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
12.5%
1/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/6
|
8.3%
1/12
|
8.3%
1/12
|
0.00%
0/12
|
12.5%
1/8
|
8.6%
3/35
|
0.00%
0/4
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/6
|
0.00%
0/12
|
16.7%
2/12
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/35
|
25.0%
1/4
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/6
|
16.7%
2/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
11.4%
4/35
|
0.00%
0/4
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
5.7%
2/35
|
0.00%
0/4
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/35
|
25.0%
1/4
|
|
Eye disorders
Eyelid oedema
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Eye disorders
Scotoma
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Eye disorders
Vision blurred
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Abdominal distension
|
66.7%
4/6
|
16.7%
2/12
|
16.7%
2/12
|
25.0%
3/12
|
0.00%
0/8
|
11.4%
4/35
|
25.0%
1/4
|
|
Gastrointestinal disorders
Abdominal pain
|
50.0%
3/6
|
41.7%
5/12
|
25.0%
3/12
|
33.3%
4/12
|
0.00%
0/8
|
28.6%
10/35
|
25.0%
1/4
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/6
|
8.3%
1/12
|
8.3%
1/12
|
16.7%
2/12
|
12.5%
1/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Gastrointestinal disorders
Abnormal faeces
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
25.0%
1/4
|
|
Gastrointestinal disorders
Constipation
|
16.7%
1/6
|
16.7%
2/12
|
8.3%
1/12
|
16.7%
2/12
|
37.5%
3/8
|
2.9%
1/35
|
25.0%
1/4
|
|
Nervous system disorders
Dizziness
|
0.00%
0/6
|
0.00%
0/12
|
16.7%
2/12
|
8.3%
1/12
|
0.00%
0/8
|
8.6%
3/35
|
0.00%
0/4
|
|
Nervous system disorders
Dysaesthesia
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Nervous system disorders
Headache
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
8.3%
1/12
|
0.00%
0/8
|
5.7%
2/35
|
25.0%
1/4
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Nervous system disorders
Neurotoxicity
|
0.00%
0/6
|
0.00%
0/12
|
16.7%
2/12
|
0.00%
0/12
|
0.00%
0/8
|
17.1%
6/35
|
0.00%
0/4
|
|
Nervous system disorders
Paraesthesia
|
33.3%
2/6
|
8.3%
1/12
|
25.0%
3/12
|
25.0%
3/12
|
25.0%
2/8
|
22.9%
8/35
|
25.0%
1/4
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
25.0%
1/4
|
|
Nervous system disorders
Polyneuropathy
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Nervous system disorders
Presyncope
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Nervous system disorders
Speech disorder
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
8.6%
3/35
|
25.0%
1/4
|
|
Psychiatric disorders
Depression
|
16.7%
1/6
|
0.00%
0/12
|
16.7%
2/12
|
8.3%
1/12
|
0.00%
0/8
|
5.7%
2/35
|
0.00%
0/4
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
16.7%
2/12
|
12.5%
1/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Psychiatric disorders
Restlessness
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/6
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/6
|
0.00%
0/12
|
16.7%
2/12
|
8.3%
1/12
|
0.00%
0/8
|
5.7%
2/35
|
0.00%
0/4
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/6
|
16.7%
2/12
|
8.3%
1/12
|
8.3%
1/12
|
12.5%
1/8
|
22.9%
8/35
|
0.00%
0/4
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/6
|
8.3%
1/12
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/8
|
14.3%
5/35
|
0.00%
0/4
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/6
|
0.00%
0/12
|
16.7%
2/12
|
0.00%
0/12
|
12.5%
1/8
|
2.9%
1/35
|
0.00%
0/4
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
16.7%
1/6
|
0.00%
0/12
|
8.3%
1/12
|
16.7%
2/12
|
25.0%
2/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
1/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
12.5%
1/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Vascular disorders
Hypertension
|
16.7%
1/6
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Vascular disorders
Hypotension
|
0.00%
0/6
|
8.3%
1/12
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
|
Vascular disorders
Peripheral coldness
|
0.00%
0/6
|
0.00%
0/12
|
8.3%
1/12
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/35
|
0.00%
0/4
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER