Trial Outcomes & Findings for A Study of Olaratumab (IMC-3G3) in Prostate Cancer (NCT NCT01204710)
NCT ID: NCT01204710
Last Updated: 2019-09-20
Results Overview
PFS is measured from randomization to the earliest date of the following events: PD according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version (v) 1.1, is a ≥20% increase in the sum of diameter of the target lesions taking as reference the smallest sum on study and an absolute increase in the sum diameter of ≥5 millimeter (mm), the appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions, unequivocal evidence of progression by bone scan, clinical progression or death from any cause. For participants who had no documented PD or death or had started new anti-cancer therapy or were lost to follow-up, PFS was censored at their last tumor assessment.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
123 participants
Primary outcome timeframe
Randomization to Measured PD or Death Due to Any Cause Up to 23 Months
Results posted on
2019-09-20
Participant Flow
A participant was considered to have completed the study if he or she experienced progressive disease (PD) or had died.
Participant milestones
| Measure |
Olaratumab (IMC-3G3) + Mitoxantrone
15 milligrams per kilogram (mg/kg) olaratumab was administered intravenously (IV) on Days 1 and 8 of each 21-day cycle, followed by 12 milligrams per square meter (mg/m²) mitoxantrone IV on Day 1 of each 21-day cycle with 5 milligrams (mg) prednisone orally (PO) twice daily (BID) on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone: Optional Olaratumab Monotherapy
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment. 15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
|---|---|---|
|
Randomization Treatment
STARTED
|
63
|
60
|
|
Randomization Treatment
Received ≥1 Dose of Study Drug
|
62
|
59
|
|
Randomization Treatment
COMPLETED
|
49
|
47
|
|
Randomization Treatment
NOT COMPLETED
|
14
|
13
|
|
Optional Olaratumab Monotherapy
STARTED
|
0
|
19
|
|
Optional Olaratumab Monotherapy
COMPLETED
|
0
|
16
|
|
Optional Olaratumab Monotherapy
NOT COMPLETED
|
0
|
3
|
Reasons for withdrawal
| Measure |
Olaratumab (IMC-3G3) + Mitoxantrone
15 milligrams per kilogram (mg/kg) olaratumab was administered intravenously (IV) on Days 1 and 8 of each 21-day cycle, followed by 12 milligrams per square meter (mg/m²) mitoxantrone IV on Day 1 of each 21-day cycle with 5 milligrams (mg) prednisone orally (PO) twice daily (BID) on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone: Optional Olaratumab Monotherapy
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment. 15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
|---|---|---|
|
Randomization Treatment
Lost to Follow-up
|
1
|
0
|
|
Randomization Treatment
Withdrawal by Subject
|
6
|
5
|
|
Randomization Treatment
Physician Decision
|
3
|
2
|
|
Randomization Treatment
Entry criteria not met
|
0
|
1
|
|
Randomization Treatment
Adverse Event
|
4
|
2
|
|
Randomization Treatment
Sponsor Decision
|
0
|
1
|
|
Randomization Treatment
Worsening of General condition
|
0
|
1
|
|
Randomization Treatment
Moved and Followed for Survival
|
0
|
1
|
|
Optional Olaratumab Monotherapy
Olaratumab Intolerance
|
0
|
1
|
|
Optional Olaratumab Monotherapy
Physician Decision
|
0
|
1
|
|
Optional Olaratumab Monotherapy
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
A Study of Olaratumab (IMC-3G3) in Prostate Cancer
Baseline characteristics by cohort
| Measure |
Olaratumab + Mitoxantrone
n=62 Participants
15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle, followed by 12 mg/m² mitoxantrone IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone: Optional Olaratumab Monotherapy
n=59 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment. 15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
Total
n=121 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
|
20 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
35 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
42 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
62 Participants
n=5 Participants
|
59 Participants
n=7 Participants
|
121 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
60 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
116 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
62 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
120 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 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
|
|
Region of Enrollment
Hungary
|
6 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Region of Enrollment
Czechia
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
17 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
11 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
15 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
5 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Randomization to Measured PD or Death Due to Any Cause Up to 23 MonthsPopulation: All randomized participants who received ≥1 dose of study drug. The number of participants censored was 10 for olaratumab + mitoxantrone group and 5 for mitoxantrone group.
PFS is measured from randomization to the earliest date of the following events: PD according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version (v) 1.1, is a ≥20% increase in the sum of diameter of the target lesions taking as reference the smallest sum on study and an absolute increase in the sum diameter of ≥5 millimeter (mm), the appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions, unequivocal evidence of progression by bone scan, clinical progression or death from any cause. For participants who had no documented PD or death or had started new anti-cancer therapy or were lost to follow-up, PFS was censored at their last tumor assessment.
Outcome measures
| Measure |
Olaratumab + Mitoxantrone
n=62 Participants
15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle, followed by 12 mg/m² mitoxantrone IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone
n=59 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
Mitoxantrone: Optional Olaratumab Monotherapy
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment. 15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
Mitoxantrone (LE)
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
|---|---|---|---|---|
|
Progression-Free Survival (PFS)
|
2.3 months
Interval 2.2 to 2.8
|
2.4 months
Interval 2.2 to 3.8
|
—
|
—
|
SECONDARY outcome
Timeframe: Randomization to Death Due to Any Cause Up to 36 MonthsPopulation: All randomized participants who received ≥1 dose of study drug. The number of participants censored was 12 for olaratumab + mitoxantrone group and 13 for mitoxantrone group.
OS was defined as the time from the date of randomization to the date of death from any cause. If the participants were alive at the end of the follow-up period or were lost to follow-up, OS time was censored on the last date the participant was known to be alive.
Outcome measures
| Measure |
Olaratumab + Mitoxantrone
n=62 Participants
15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle, followed by 12 mg/m² mitoxantrone IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone
n=59 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
Mitoxantrone: Optional Olaratumab Monotherapy
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment. 15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
Mitoxantrone (LE)
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
|---|---|---|---|---|
|
Overall Survival (OS)
|
14.2 months
Interval 12.2 to 16.0
|
12.8 months
Interval 8.1 to 16.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Randomization to Objective PD or Death Up to 23 MonthsPopulation: All randomized participants who received at least ≥1 dose of study drug and had measurable disease.
Best response is categorized using the RECIST v1.1 guidelines. CR is the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to \<10 mm. PR is a ≥30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the pretreatment sum diameter. Percentage of participants = (number of participants who had CR or PR) / (number of participants treated) \* 100.
Outcome measures
| Measure |
Olaratumab + Mitoxantrone
n=30 Participants
15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle, followed by 12 mg/m² mitoxantrone IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone
n=32 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
Mitoxantrone: Optional Olaratumab Monotherapy
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment. 15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
Mitoxantrone (LE)
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
|---|---|---|---|---|
|
Percentage of Participants Who Achieved a Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
|
10.0 percentage of participants
Interval 3.5 to 25.6
|
3.1 percentage of participants
Interval 0.6 to 15.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Pretreatment to PD Up to 23 MonthsPopulation: All randomized participants who received ≥1 dose of study drug.
Decrease in PSA ≥50% from pretreatment required confirmation no less than 3 weeks after the initial suggestion of response and occurring prior to documentation of PD. Percentage of participants = (number of participants who had ≥50% decrease in PSA at any time) / (number of participants treated) \* 100.
Outcome measures
| Measure |
Olaratumab + Mitoxantrone
n=62 Participants
15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle, followed by 12 mg/m² mitoxantrone IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone
n=59 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
Mitoxantrone: Optional Olaratumab Monotherapy
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment. 15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
Mitoxantrone (LE)
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
|---|---|---|---|---|
|
Percentage of Participants With a ≥50% Decrease in Prostate Specific Androgen (PSA) From Pretreatment to Any Time
|
22.6 percentage of participants
Interval 14.0 to 34.4
|
18.6 percentage of participants
Interval 10.7 to 30.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Pretreatment through Week 12Population: All randomized participants who received ≥1 dose of study drug.
Percentage of participants = (number of participants who had ≥30% decrease in PSA at Week 12) / (number of participants treated) \* 100.
Outcome measures
| Measure |
Olaratumab + Mitoxantrone
n=62 Participants
15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle, followed by 12 mg/m² mitoxantrone IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone
n=59 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
Mitoxantrone: Optional Olaratumab Monotherapy
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment. 15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
Mitoxantrone (LE)
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
|---|---|---|---|---|
|
Percentage of Participants With a ≥30% Decrease in PSA From Pretreatment to Week 12
|
22.6 percentage of participants
Interval 14.0 to 34.4
|
16.9 percentage of participants
Interval 9.5 to 28.5
|
—
|
—
|
SECONDARY outcome
Timeframe: From Start of Treatment Through Study Completion Up to 36 monthsPopulation: All randomized participants who received at least 1 dose of study drug.
Data presented are the number of participants who experienced serious adverse events (SAEs) and other nonserious adverse events (AEs). For participants in mitoxantrone group who had PD and chose optional IMC-3G3 follow-on treatment, the baseline was defined as the last assessment prior to the start of the olaratumab treatment. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
Outcome measures
| Measure |
Olaratumab + Mitoxantrone
n=62 Participants
15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle, followed by 12 mg/m² mitoxantrone IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone
n=59 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
Mitoxantrone: Optional Olaratumab Monotherapy
n=19 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment. 15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
Mitoxantrone (LE)
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
|---|---|---|---|---|
|
Summary Listing of Participants Reporting Treatment-Emergent Adverse Events (TEAE)
SAEs
|
26 participants
|
21 participants
|
6 participants
|
—
|
|
Summary Listing of Participants Reporting Treatment-Emergent Adverse Events (TEAE)
AEs
|
52 participants
|
51 participants
|
15 participants
|
—
|
SECONDARY outcome
Timeframe: Randomization to Measured PD or Death Due to Any Cause Up to 23 MonthsPopulation: All randomized participants who had evaluable data for CTC counts at baseline. The CTC counts assessment across both arms, high and low expression, was pre-specified in the statistical analysis plan.
High expression (HE) of CTC was defined as having CTC counts ≥5 cells/7.5 milliliter (mL) and low expression (LE) of CTC was defined as having CTC counts \<5 cells/7.5 mL. PFS is measured from randomization to the earliest date of the following events: PD according to RECIST criteria v. 1.1, is a ≥20% increase in the sum diameter of the target lesions taking as reference the smallest sum on study and an absolute increase in the sum diameter of ≥5 mm, the appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions, unequivocal evidence of progression by bone scan, clinical progression or death from any cause.
Outcome measures
| Measure |
Olaratumab + Mitoxantrone
n=32 Participants
15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle, followed by 12 mg/m² mitoxantrone IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone
n=32 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
Mitoxantrone: Optional Olaratumab Monotherapy
n=21 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment. 15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
Mitoxantrone (LE)
n=18 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
|---|---|---|---|---|
|
PFS Based on Baseline Circulating Tumor Cells (CTC) Counts
|
2.32 months
Interval 2.1 to 2.79
|
2.23 months
Interval 2.1 to 2.4
|
2.38 months
Interval 2.14 to 7.2
|
4.91 months
Interval 2.4 to 11.73
|
SECONDARY outcome
Timeframe: Randomization to Death Due to Any Cause Up to 36 MonthsPopulation: All randomized participants who had evaluable data for CTC counts at baseline. The CTC counts assessment across both arms, high and low expression, was pre-specified in the statistical analysis plan.
HE of CTC was defined as having CTC counts ≥5 cells/7.5 mL and LE of CTC was defined as having CTC counts \<5 cells/7.5 mL. OS was defined as the time from the date of randomization to the date of death from any cause.
Outcome measures
| Measure |
Olaratumab + Mitoxantrone
n=32 Participants
15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle, followed by 12 mg/m² mitoxantrone IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone
n=32 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
Mitoxantrone: Optional Olaratumab Monotherapy
n=21 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment. 15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
Mitoxantrone (LE)
n=18 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
|---|---|---|---|---|
|
OS Based on Baseline CTC Counts
|
12.85 months
Interval 7.1 to 15.18
|
8.10 months
Interval 5.82 to 13.14
|
16.49 months
Interval 9.13 to 28.12
|
23.00 months
Interval 11.93 to
The upper confidence interval for median OS is inestimable when the curve representing the upper confidence limits for the survivor function falls above the 0.5 line.
|
SECONDARY outcome
Timeframe: BaselinePopulation: All randomized participants who received at least 1 dose of study drug and provided tissue specimens from the initial diagnosis for PDGFRα protein expression analysis.
PDGFRα protein expression (pretreatment) by IHC was assessed in tumor cells, and was provided as a dichotomous variable with "positive" and "negative" expression. "Positive" corresponds to weak intensity membranous staining comprising greater than 30% of the tumor and/or moderate to strong intensity membranous staining comprising greater than 5% of the tumor. "Negative" corresponds to staining that does not meet these requirements.
Outcome measures
| Measure |
Olaratumab + Mitoxantrone
n=14 Participants
15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle, followed by 12 mg/m² mitoxantrone IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone
n=9 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
Mitoxantrone: Optional Olaratumab Monotherapy
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment. 15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
Mitoxantrone (LE)
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
|---|---|---|---|---|
|
Number of Participants With Negative Platelet-Derived Growth Factor Receptor Alpha (PDGFRα) Protein Expression by Immunohistochemistry (IHC)
|
14 participants
|
9 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: From Start of Treatment up to 9 MonthsPopulation: All randomized participants who received ≥1 dose of study drug and had evaluable baseline and evaluable post-baseline antibody data. The participants analyzed under Mitoxantrone are those in control arm receiving subsequent optional olaratumab monotherapy.
Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.
Outcome measures
| Measure |
Olaratumab + Mitoxantrone
n=52 Participants
15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle, followed by 12 mg/m² mitoxantrone IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone
n=11 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
Mitoxantrone: Optional Olaratumab Monotherapy
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment. 15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
Mitoxantrone (LE)
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
|---|---|---|---|---|
|
Percentage of Participants With Anti-Olaratumab Antibody Assessment (Immunogenicity)
|
3.8 percent of participants
|
0 percent of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 of Cycles 1, 2 and 3, and Day 8 of Cycles 1 and 3 (21-day cycle)Population: Zero participants were analyzed. An insufficient amount of samples were collected to obtain this measure.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: From Start of Treatment through Study Completion up to 36 MonthsPopulation: All randomized participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
Olaratumab + Mitoxantrone
n=62 Participants
15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle, followed by 12 mg/m² mitoxantrone IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone
n=59 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
Mitoxantrone: Optional Olaratumab Monotherapy
n=19 Participants
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment. 15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
Mitoxantrone (LE)
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
|---|---|---|---|---|
|
Number of Participants Who Died During Study
Due to PD
|
43 participants
|
27 participants
|
12 participants
|
—
|
|
Number of Participants Who Died During Study
Due to AEs
|
4 participants
|
3 participants
|
1 participants
|
—
|
|
Number of Participants Who Died During Study
Due to Other reasons
|
3 participants
|
2 participants
|
1 participants
|
—
|
Adverse Events
Olaratumab + Mitoxantrone
Serious events: 26 serious events
Other events: 52 other events
Deaths: 0 deaths
Mitoxantrone
Serious events: 21 serious events
Other events: 51 other events
Deaths: 0 deaths
Mitoxantrone: Optional Olaratumab Monotherapy
Serious events: 6 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Olaratumab + Mitoxantrone
n=62 participants at risk
15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle, followed by 12 mg/m² mitoxantrone IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone
n=59 participants at risk
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
Mitoxantrone: Optional Olaratumab Monotherapy
n=19 participants at risk
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment.15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Agranulocytosis
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
Blood and lymphatic system disorders
Anaemia
|
8.1%
5/62 • Number of events 5
|
6.8%
4/59 • Number of events 4
|
5.3%
1/19 • Number of events 1
|
|
Blood and lymphatic system disorders
Anaemia of malignant disease
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.6%
1/62 • Number of events 1
|
1.7%
1/59 • Number of events 2
|
0.00%
0/19
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/62
|
3.4%
2/59 • Number of events 2
|
0.00%
0/19
|
|
Blood and lymphatic system disorders
Neutropenia
|
3.2%
2/62 • Number of events 4
|
5.1%
3/59 • Number of events 3
|
0.00%
0/19
|
|
Blood and lymphatic system disorders
Pancytopenia
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
4.8%
3/62 • Number of events 3
|
0.00%
0/59
|
0.00%
0/19
|
|
Cardiac disorders
Atrial fibrillation
|
3.2%
2/62 • Number of events 2
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
Cardiac disorders
Atrial flutter
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/62
|
0.00%
0/59
|
5.3%
1/19 • Number of events 1
|
|
Cardiac disorders
Cardiac failure chronic
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Cardiac disorders
Cardiac failure congestive
|
1.6%
1/62 • Number of events 3
|
0.00%
0/59
|
0.00%
0/19
|
|
Cardiac disorders
Congestive cardiomyopathy
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Cardiac disorders
Myocardial ischaemia
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
Ear and labyrinth disorders
Vertigo
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
5.3%
1/19 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
5.3%
1/19 • Number of events 1
|
|
Gastrointestinal disorders
Periodontitis
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
General disorders
Asthenia
|
1.6%
1/62 • Number of events 2
|
0.00%
0/59
|
5.3%
1/19 • Number of events 1
|
|
General disorders
Fatigue
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
General disorders
General physical health deterioration
|
1.6%
1/62 • Number of events 1
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
General disorders
Localised oedema
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
General disorders
Multi-organ failure
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
General disorders
Oedema peripheral
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
General disorders
Pain
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
10.5%
2/19 • Number of events 2
|
|
Immune system disorders
Anaphylactic reaction
|
3.2%
2/62 • Number of events 2
|
0.00%
0/59
|
0.00%
0/19
|
|
Immune system disorders
Anaphylactic shock
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
5.3%
1/19 • Number of events 1
|
|
Immune system disorders
Hypersensitivity
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
Infections and infestations
Erysipelas
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Infections and infestations
Gastroenteritis escherichia coli
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Infections and infestations
Pneumonia
|
1.6%
1/62 • Number of events 1
|
5.1%
3/59 • Number of events 3
|
0.00%
0/19
|
|
Infections and infestations
Rectal abscess
|
0.00%
0/62
|
0.00%
0/59
|
5.3%
1/19 • Number of events 1
|
|
Infections and infestations
Respiratory tract infection
|
3.2%
2/62 • Number of events 2
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
Infections and infestations
Septic shock
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Infections and infestations
Urinary tract infection
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Infections and infestations
Urosepsis
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
Injury, poisoning and procedural complications
Cystitis radiation
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Injury, poisoning and procedural complications
Femur fracture
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Injury, poisoning and procedural complications
Incorrect dose administered
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Investigations
General physical condition abnormal
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
5.3%
1/19 • Number of events 1
|
|
Metabolism and nutrition disorders
Cachexia
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
5.3%
1/19 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
5.3%
1/19 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
1.6%
1/62 • Number of events 3
|
0.00%
0/59
|
0.00%
0/19
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
Nervous system disorders
Cerebrovascular accident
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Nervous system disorders
Depressed level of consciousness
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Nervous system disorders
Facial paresis
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Nervous system disorders
Ischaemic stroke
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Nervous system disorders
Muscle spasticity
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Nervous system disorders
Paraparesis
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Nervous system disorders
Paraplegia
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Nervous system disorders
Spinal cord compression
|
1.6%
1/62 • Number of events 1
|
3.4%
2/59 • Number of events 2
|
0.00%
0/19
|
|
Psychiatric disorders
Alcoholism
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
Renal and urinary disorders
Renal failure acute
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
4.8%
3/62 • Number of events 3
|
0.00%
0/59
|
0.00%
0/19
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary infarction
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
0.00%
0/19
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
Vascular disorders
Deep vein thrombosis
|
3.2%
2/62 • Number of events 2
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
Other adverse events
| Measure |
Olaratumab + Mitoxantrone
n=62 participants at risk
15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle, followed by 12 mg/m² mitoxantrone IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone was restricted to ≤144 mg/m²).
After 12 cycles, participants continued to receive 15 mg/kg olaratumab IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day until withdrawal criteria were met.
|
Mitoxantrone
n=59 participants at risk
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
|
Mitoxantrone: Optional Olaratumab Monotherapy
n=19 participants at risk
12 mg/m² mitoxantrone was administered IV on Day 1 of each 21-day cycle with 5 mg prednisone PO BID on each day.
Mitoxantrone was administered for up to 12 cycles (total cumulative dose of mitoxantrone is restricted to ≤144 mg/m²).
Participants who experienced PD had the option to receive olaratumab monotherapy treatment.15 mg/kg olaratumab was administered IV on Days 1 and 8 of each 21-day cycle with 5 mg prednisone PO BID on each day. Participants received treatment until withdrawal criteria were met.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
27.4%
17/62 • Number of events 41
|
25.4%
15/59 • Number of events 33
|
15.8%
3/19 • Number of events 4
|
|
Blood and lymphatic system disorders
Leukopenia
|
14.5%
9/62 • Number of events 25
|
13.6%
8/59 • Number of events 13
|
0.00%
0/19
|
|
Blood and lymphatic system disorders
Neutropenia
|
30.6%
19/62 • Number of events 44
|
18.6%
11/59 • Number of events 28
|
0.00%
0/19
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
12.9%
8/62 • Number of events 19
|
10.2%
6/59 • Number of events 17
|
5.3%
1/19 • Number of events 1
|
|
Ear and labyrinth disorders
Vertigo
|
3.2%
2/62 • Number of events 2
|
6.8%
4/59 • Number of events 6
|
0.00%
0/19
|
|
Gastrointestinal disorders
Abdominal pain
|
3.2%
2/62 • Number of events 2
|
3.4%
2/59 • Number of events 3
|
5.3%
1/19 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/62
|
5.1%
3/59 • Number of events 4
|
0.00%
0/19
|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/62
|
0.00%
0/59
|
5.3%
1/19 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
8.1%
5/62 • Number of events 6
|
18.6%
11/59 • Number of events 14
|
15.8%
3/19 • Number of events 4
|
|
Gastrointestinal disorders
Diarrhoea
|
19.4%
12/62 • Number of events 15
|
11.9%
7/59 • Number of events 8
|
0.00%
0/19
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/62
|
8.5%
5/59 • Number of events 6
|
0.00%
0/19
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
5.3%
1/19 • Number of events 1
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
0.00%
0/62
|
0.00%
0/59
|
5.3%
1/19 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
24.2%
15/62 • Number of events 19
|
23.7%
14/59 • Number of events 19
|
10.5%
2/19 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
8.1%
5/62 • Number of events 5
|
5.1%
3/59 • Number of events 3
|
5.3%
1/19 • Number of events 1
|
|
General disorders
Asthenia
|
29.0%
18/62 • Number of events 39
|
22.0%
13/59 • Number of events 23
|
26.3%
5/19 • Number of events 5
|
|
General disorders
Fatigue
|
17.7%
11/62 • Number of events 11
|
18.6%
11/59 • Number of events 13
|
15.8%
3/19 • Number of events 3
|
|
General disorders
Infusion related reaction
|
1.6%
1/62 • Number of events 1
|
0.00%
0/59
|
10.5%
2/19 • Number of events 3
|
|
General disorders
Oedema peripheral
|
9.7%
6/62 • Number of events 8
|
6.8%
4/59 • Number of events 4
|
5.3%
1/19 • Number of events 1
|
|
General disorders
Pyrexia
|
6.5%
4/62 • Number of events 8
|
11.9%
7/59 • Number of events 7
|
5.3%
1/19 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
3.2%
2/62 • Number of events 2
|
1.7%
1/59 • Number of events 2
|
5.3%
1/19 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
1.6%
1/62 • Number of events 1
|
1.7%
1/59 • Number of events 1
|
5.3%
1/19 • Number of events 1
|
|
Investigations
Ejection fraction decreased
|
1.6%
1/62 • Number of events 1
|
5.1%
3/59 • Number of events 3
|
0.00%
0/19
|
|
Investigations
Gamma-glutamyltransferase increased
|
3.2%
2/62 • Number of events 2
|
5.1%
3/59 • Number of events 5
|
0.00%
0/19
|
|
Investigations
Weight decreased
|
3.2%
2/62 • Number of events 2
|
8.5%
5/59 • Number of events 6
|
0.00%
0/19
|
|
Metabolism and nutrition disorders
Decreased appetite
|
17.7%
11/62 • Number of events 15
|
10.2%
6/59 • Number of events 10
|
15.8%
3/19 • Number of events 5
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
1.6%
1/62 • Number of events 1
|
1.7%
1/59 • Number of events 1
|
5.3%
1/19 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypovitaminosis
|
0.00%
0/62
|
0.00%
0/59
|
5.3%
1/19 • Number of events 1
|
|
Metabolism and nutrition disorders
Vitamin b12 deficiency
|
0.00%
0/62
|
1.7%
1/59 • Number of events 1
|
5.3%
1/19 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.3%
7/62 • Number of events 7
|
5.1%
3/59 • Number of events 6
|
0.00%
0/19
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.7%
6/62 • Number of events 8
|
11.9%
7/59 • Number of events 8
|
10.5%
2/19 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
11.3%
7/62 • Number of events 10
|
8.5%
5/59 • Number of events 5
|
5.3%
1/19 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/62
|
1.7%
1/59 • Number of events 2
|
5.3%
1/19 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle atrophy
|
0.00%
0/62
|
0.00%
0/59
|
5.3%
1/19 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.5%
4/62 • Number of events 5
|
1.7%
1/59 • Number of events 1
|
0.00%
0/19
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
1.6%
1/62 • Number of events 1
|
6.8%
4/59 • Number of events 4
|
10.5%
2/19 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
11.3%
7/62 • Number of events 7
|
5.1%
3/59 • Number of events 4
|
0.00%
0/19
|
|
Nervous system disorders
Dizziness
|
3.2%
2/62 • Number of events 3
|
5.1%
3/59 • Number of events 4
|
0.00%
0/19
|
|
Nervous system disorders
Dysgeusia
|
3.2%
2/62 • Number of events 2
|
5.1%
3/59 • Number of events 4
|
0.00%
0/19
|
|
Nervous system disorders
Headache
|
6.5%
4/62 • Number of events 6
|
8.5%
5/59 • Number of events 17
|
5.3%
1/19 • Number of events 1
|
|
Nervous system disorders
Paraesthesia
|
1.6%
1/62 • Number of events 1
|
5.1%
3/59 • Number of events 3
|
0.00%
0/19
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/62
|
3.4%
2/59 • Number of events 2
|
5.3%
1/19 • Number of events 1
|
|
Psychiatric disorders
Depression
|
3.2%
2/62 • Number of events 2
|
1.7%
1/59 • Number of events 1
|
5.3%
1/19 • Number of events 1
|
|
Renal and urinary disorders
Haematuria
|
3.2%
2/62 • Number of events 3
|
6.8%
4/59 • Number of events 5
|
0.00%
0/19
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/62
|
0.00%
0/59
|
5.3%
1/19 • Number of events 2
|
|
Renal and urinary disorders
Urinary incontinence
|
1.6%
1/62 • Number of events 1
|
6.8%
4/59 • Number of events 4
|
0.00%
0/19
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/62
|
0.00%
0/59
|
15.8%
3/19 • Number of events 4
|
|
Reproductive system and breast disorders
Pelvic pain
|
4.8%
3/62 • Number of events 3
|
3.4%
2/59 • Number of events 2
|
10.5%
2/19 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.5%
4/62 • Number of events 4
|
10.2%
6/59 • Number of events 6
|
0.00%
0/19
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
6.5%
4/62 • Number of events 4
|
6.8%
4/59 • Number of events 5
|
5.3%
1/19 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
3.2%
2/62 • Number of events 2
|
1.7%
1/59 • Number of events 2
|
5.3%
1/19 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Hypoaesthesia facial
|
0.00%
0/62
|
0.00%
0/59
|
5.3%
1/19 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/62
|
3.4%
2/59 • Number of events 2
|
10.5%
2/19 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
0.00%
0/62
|
0.00%
0/59
|
5.3%
1/19 • Number of events 1
|
|
Vascular disorders
Hypertension
|
8.1%
5/62 • Number of events 7
|
3.4%
2/59 • Number of events 6
|
0.00%
0/19
|
|
Vascular disorders
Hypotension
|
0.00%
0/62
|
5.1%
3/59 • Number of events 3
|
0.00%
0/19
|
|
Vascular disorders
Thrombosis
|
0.00%
0/62
|
0.00%
0/59
|
5.3%
1/19 • Number of events 1
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. Sponsor may request publication delay up to 90 days to seek patent protection.
- Publication restrictions are in place
Restriction type: OTHER