A Study of Olaratumab (LY3012207), Doxorubicin, and Ifosfamide in Participants With Advanced or Metastatic Soft Tissue Sarcoma

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03283696
• Collaborator: (none)
• Enrollment: 24
• Locations: 6
• Arm: 1
• Actual Duration (Months): 22.2
• Patients Per Site: 4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety of ifosfamide when added to the combination regimen of olaratumab and doxorubicin in participants with advanced or metastatic soft tissue sarcoma (STS).

Condition or Disease	Intervention/Treatment	Phase
Soft Tissue Sarcoma	Drug: Olaratumab; Drug: Doxorubicin; Drug: Ifosfamide; Drug: Mesna	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b Study of Olaratumab, Doxorubicin and Ifosfamide in the Treatment of Patients With Advanced or Metastatic Soft Tissue Sarcoma
• Actual Study Start Date: Oct 18, 2017
• Actual Primary Completion Date: Apr 29, 2019
• Actual Study Completion Date: Aug 25, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Olaratumab + Doxorubicin + Ifosfamide + Mesna Olaratumab 15 milligrams per kilogram (mg/kg) on Days 1 and 8 of a 21-day cycle, in combination with doxorubicin and ifosfamide was administered. When the safety of the 15-mg/kg dose of olaratumab was established, a 20-mg/kg loading dose cycle of olaratumab on Days 1 and 8 of a 21-day cycle in Cycle 1 only, followed by 15 mg/kg on Days 1 and 8 of subsequent cycles in combination with doxorubicin and ifosfamide plus mesna, was administered.

Drug: Olaratumab; Administered IV; Other Names: LY3012207 ; Drug: Doxorubicin; Administered IV; Drug: Ifosfamide; Administered IV; Drug: Mesna; Administered per standard of care

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs) [Cycle 1 (Up To 24 days)]

   A Dose Limiting Toxicity is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfills any one of the following criteria, graded according to the NCI-CTCAE Version 4.0: Grade 3 or 4 febrile neutropenia, or sepsis., or Grade 4 neutropenia lasting 7 days or longer. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by hemorrhage. Nonhematologic Grade ≥3 toxicity, except for toxicities (such as nausea, vomiting, transient electrolyte abnormalities, or diarrhoea) that can be controlled with optimal medical management within 48 hours or clinically non-significant laboratory abnormalities.

Secondary Outcome Measures

1. Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab [Cycle 1 - Day 1 (predose, end of infusion, 2 hours post olaratumab (olara), 6 hours post olara, 24 hours post olara, 72 hours post olara), Day 8 (predose, end of infusion, 2 hours post-olara, 6 hours post olara, 48 hours post olara, 168 hours post olara)]

   PK: Cmax of olaratumab.

2. PK: Maximum Serum Concentration (Cmax,ss) of Olaratumab at Steady-state [Cycle 3 - Day 1 (predose, end of infusion, 2 hours post olara, 5 hours post olara, 24 hours post olara, 72 hours post olara), Day 8 (predose, end of infusion, 2 hours post-olara, 5 hours post olara, 48 hours post olara, 168 hours post olara)]

   PK: Cmax of olaratumab at steady-state.

3. PK: Trough Serum Concentration (Cmin) [Cycle 1 - Day 1 (predose, end of infusion, 2 hours post olaratumab (olara), 6 hours post olara, 24 hours post olara, 72 hours post olara), Day 8 (predose, end of infusion, 2 hours post-olara, 6 hours post olara, 48 hours post olara, 168 hours post olara)]

   PK: Cmin of olaratumab.

4. PK: Trough Serum Concentration (Cmin,ss) of Olaratumab at Steady-state [Cycle 3 - Day 1 (predose, end of infusion, 2 hours post olara, 5 hours post olara, 24 hours post olara, 72 hours post olara), Day 8 (predose, end of infusion, 2 hours post-olara, 5 hours post olara, 48 hours post olara, 168 hours post olara)]

   PK: Cmin of olaratumab at steady-state.

5. Number of Participants With Anti-Olaratumab Antibodies [Baseline through Follow-up (Up To 21 Months)]

   Participants with treatment-emergent anti-drug antibody (TE ADA) positive were 1) a participant with a 4-fold (2 dilutions) increase over a positive baseline antibody titer; or 2) for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.

6. Objective Response Rate (ORR): Number of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) [Baseline up to Short-Term Follow-Up Period (Up To 21 Months)]

   Objective response rate is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

7. Progression Free Survival (PFS) [Baseline to Objective Disease Progression or Death Due to Any Cause (Up To 21 Months)]

   Progression-free survival time was measured from randomization until the date of objective progression as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), or death from any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment, if available, or date of randomization if no post-baseline radiographic assessment is available.

8. Duration of Response (DoR) [Date of Complete Response (CR) or Partial Response (PR) to Objective Disease Progression or Death Due to Any Cause (Up To 21 Months)]

   Duration of response is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment.

9. Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) [Baseline until Disease Progression or Death Due to Any Cause (Up To 21 Months)]

   Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

10. Overall Survival (OS) [Baseline to Date of Death Due to Any Cause (Up To 21 Months)]

    Overall survival is defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date for a particular analysis, overall survival duration was censored for that analysis at the date of last prior contact.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have a histological diagnosis of advanced STS (by local pathology review), for which treatment with doxorubicin, ifosfamide and mesna is deemed appropriate by the investigator.

• Have measurable or nonmeasurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

• Have adequate hematologic, organ and coagulation function within 2 weeks (14 days) prior to enrollment.

• Have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group scale.

• Have received no prior lines of systemic therapy and are suitable to receive doxorubicin, ifosfamide and mesna. All previous anticancer treatments must have completed ≥3 weeks (21 days) prior to the first dose of study treatment.

• Have left ventricular ejection fraction (LVEF) ≥50% assessed within 28 days prior to enrollment.

• Have resolution of Adverse Events (AEs), with the exception of alopecia, and of all clinically significant toxic effects of prior locoregional therapy, surgery or radiotherapy to ≤Grade 1, by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0.

• Have sufficient available material from archived formalin-fixed paraffin-embedded tumor tissue for biomarker-related studies. If such tissue is not available, a newly obtained core or excisional biopsy of a tumor lesion must be performed.

• If male, must be sterile or agree to use an effective method of contraception or a highly effective method of contraception during the study and for at least 12 weeks following the last dose of study treatment.

• If female and of child-bearing potential, must:

1. have a negative serum pregnancy test at the time of enrollment,

2. have a negative urine pregnancy test within 24 hours prior to the first dose of study treatment, and

3. agree to use a highly effective method of contraception during the study and for 3 months following the last dose of study treatment.

• Have a life expectancy of at least 3 months, in the opinion of the investigator.

Exclusion Criteria:

• Are currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.

• Have participated within the past 30 days in a clinical trial involving an investigational product. If the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed.

• Have previously completed or withdrawn from any study investigating olaratumab.

• Have received prior treatment with olaratumab, doxorubicin, or ifosfamide, or have participated in other trials investigating olaratumab.

• Have received prior radiotherapy of the mediastinal/pericardial area or whole pelvis radiation.

• Have known urinary outflow obstruction, or inflammation of the urinary bladder (cystitis).

• Are diagnosed with gastrointestinal stromal tumor or Kaposi sarcoma.

• Have active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of enrollment. Participants with a history of CNS metastasis (previously treated with curative intent [for example, stereotactic radiation or surgery]) that has not progressed on follow-up imaging, have been asymptomatic for at least 60 days, and are not receiving systemic corticosteroids and/or anticonvulsants are eligible. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before enrollment to rule out brain metastasis.

• Have a history of another primary malignancy, with the exception of:

1. curatively treated non-melanomatous skin cancer

2. curatively treated cervical carcinoma in situ

• Have an active fungal, bacterial and/or known viral infection including human immunodeficiency virus or viral (A, B, or C) hepatitis (screening is not required).

• Have Grade 3 or 4 peripheral neuropathy per NCI-CTCAE Version 4.0.

• Have a serious cardiac condition.

• Have a resting heart rate of >100 beats per minute (bpm).

• Have a Fridericia's QT corrected interval (QTcF) interval of >450 milliseconds (msec) for males and >470 msec for females on screening electrocardiogram (ECG) utilizing Fridericia's correction.

• Have uncontrolled intercurrent illness including, but not limited to, an ongoing/active infection requiring parenteral antibiotics.

• Have a psychiatric illness/social situation that would limit compliance with study requirements.

• Have electively planned or will require major surgery during the course of the study.

• Are females who are pregnant or breastfeeding.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami School of Medicine	Miami	Florida	United States	33136
2	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
3	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen	Germany	45122
4	HELIOS Klinikum Berlin-Buch	Berlin		Germany	13125
5	Istituto Nazionale dei Tumori	Milano	Lombardie	Italy	20133
6	Università degli Studi di Catania - Azienda Policlinico	Catania		Italy	95123

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - Jun 26, 2018
• Statistical Analysis Plan - Aug 28, 2017

More Information

Additional Information:

• A Study of Olaratumab (LY3012207), Doxorubicin, and Ifosfamide in Participants With Advanced or Metastatic Soft Tissue Sarcoma

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03283696
• Other Study ID Numbers: 16430; I5B-MC-JGDR; 2016-004287-19
• First Posted: Sep 14, 2017
• Last Update Posted: Sep 10, 2020
• Last Verified: Apr 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Sarcoma; Doxorubicin; Ifosfamide; Olaratumab

Study Results

Participant Flow

Pre-assignment Detail	Completers included participants who died from any cause, participants with progressive disease.

Arm/Group Title	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
Arm/Group Description	Participants received olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus doxorubicin 25 milligrams per meter square (mg/m^2) on days 1, 2, 3 plus ifosfamide 2.5 gram per meter square (g/m^2) per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Period Title: Overall Study
STARTED	16	8
Received at Least 1 Dose of Study Drug	16	8
COMPLETED	9	2
NOT COMPLETED	7	6

Baseline Characteristics

Arm/Group Title	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide	Total
Arm/Group Description	Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Total of all reporting groups
Overall Participants	16	8	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.6 (11.1)	49.8 (11.1)	45.0 (11.4)
Sex: Female, Male (Count of Participants)
Female	9 56.3%	5 62.5%	14 58.3%
Male	7 43.8%	3 37.5%	10 41.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 18.8%	3 37.5%	6 25%
Not Hispanic or Latino	6 37.5%	4 50%	10 41.7%
Unknown or Not Reported	7 43.8%	1 12.5%	8 33.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 6.3%	0 0%	1 4.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	15 93.8%	8 100%	23 95.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	6 37.5%	5 62.5%	11 45.8%
Italy	3 18.8%	0 0%	3 12.5%
Germany	7 43.8%	3 37.5%	10 41.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs)
Description	A Dose Limiting Toxicity is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfills any one of the following criteria, graded according to the NCI-CTCAE Version 4.0: Grade 3 or 4 febrile neutropenia, or sepsis., or Grade 4 neutropenia lasting 7 days or longer. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by hemorrhage. Nonhematologic Grade ≥3 toxicity, except for toxicities (such as nausea, vomiting, transient electrolyte abnormalities, or diarrhoea) that can be controlled with optimal medical management within 48 hours or clinically non-significant laboratory abnormalities.
Time Frame	Cycle 1 (Up To 24 days)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
Arm/Group Description	Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Measure Participants	16	8
Count of Participants [Participants]	4 25%	4 50%

2. Secondary Outcome

Title	Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab
Description	PK: Cmax of olaratumab.
Time Frame	Cycle 1 - Day 1 (predose, end of infusion, 2 hours post olaratumab (olara), 6 hours post olara, 24 hours post olara, 72 hours post olara), Day 8 (predose, end of infusion, 2 hours post-olara, 6 hours post olara, 48 hours post olara, 168 hours post olara)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
Arm/Group Description	Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Measure Participants	16	8
Cycle 1 Day 1	408 (25)	508 (27)
Cycle 1 Day 8	452 (28)	671 (24)

3. Secondary Outcome

Title	PK: Maximum Serum Concentration (Cmax,ss) of Olaratumab at Steady-state
Description	PK: Cmax of olaratumab at steady-state.
Time Frame	Cycle 3 - Day 1 (predose, end of infusion, 2 hours post olara, 5 hours post olara, 24 hours post olara, 72 hours post olara), Day 8 (predose, end of infusion, 2 hours post-olara, 5 hours post olara, 48 hours post olara, 168 hours post olara)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
Arm/Group Description	Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Measure Participants	16	8
Cycle 3 Day 1	533 (22)	494 (9)
Cycle 3 Day 8	523 (18)	545 (13)

4. Secondary Outcome

Title	PK: Trough Serum Concentration (Cmin)
Description	PK: Cmin of olaratumab.
Time Frame	Cycle 1 - Day 1 (predose, end of infusion, 2 hours post olaratumab (olara), 6 hours post olara, 24 hours post olara, 72 hours post olara), Day 8 (predose, end of infusion, 2 hours post-olara, 6 hours post olara, 48 hours post olara, 168 hours post olara)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
Arm/Group Description	Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Measure Participants	16	8
Cycle 1 Day 1	87.3 (40)	140 (45)
Cycle 1 Day 8	46.7 (105)	53.3 (143)

5. Secondary Outcome

Title	PK: Trough Serum Concentration (Cmin,ss) of Olaratumab at Steady-state
Description	PK: Cmin of olaratumab at steady-state.
Time Frame	Cycle 3 - Day 1 (predose, end of infusion, 2 hours post olara, 5 hours post olara, 24 hours post olara, 72 hours post olara), Day 8 (predose, end of infusion, 2 hours post-olara, 5 hours post olara, 48 hours post olara, 168 hours post olara)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug and had evaluable PK data.

Arm/Group Title	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
Arm/Group Description	Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Measure Participants	16	8
Cycle 3 Day 1	154 (26)	177 (17)
Cycle 3 Day 8	126 (35)	115 (32)

6. Secondary Outcome

Title	Number of Participants With Anti-Olaratumab Antibodies
Description	Participants with treatment-emergent anti-drug antibody (TE ADA) positive were 1) a participant with a 4-fold (2 dilutions) increase over a positive baseline antibody titer; or 2) for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.
Time Frame	Baseline through Follow-up (Up To 21 Months)

Outcome Measure Data

Analysis Population Description

All participants with an evaluable baseline and at least 1 post-baseline data for Anti-Olaratumab Antibodies.

Arm/Group Title	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
Arm/Group Description	Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Measure Participants	15	8
Count of Participants [Participants]	0 0%	1 12.5%

7. Secondary Outcome

Title	Objective Response Rate (ORR): Number of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR)
Description	Objective response rate is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.
Time Frame	Baseline up to Short-Term Follow-Up Period (Up To 21 Months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
Arm/Group Description	Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Measure Participants	16	8
Count of Participants [Participants]	6 37.5%	1 12.5%

8. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Progression-free survival time was measured from randomization until the date of objective progression as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), or death from any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment, if available, or date of randomization if no post-baseline radiographic assessment is available.
Time Frame	Baseline to Objective Disease Progression or Death Due to Any Cause (Up To 21 Months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug. Number of participants censored were Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide = 8 and Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide = 6.

Arm/Group Title	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
Arm/Group Description	Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Measure Participants	16	8
Median (95% Confidence Interval) [Months]	9.53	6.93

9. Secondary Outcome

Title	Duration of Response (DoR)
Description	Duration of response is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1, or the date of death from any cause in the absence of objectively determined disease progression or recurrence. Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment.
Time Frame	Date of Complete Response (CR) or Partial Response (PR) to Objective Disease Progression or Death Due to Any Cause (Up To 21 Months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug. Number of participants censored were Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide = 4 and Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide = 1.

Arm/Group Title	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
Arm/Group Description	Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Measure Participants	16	8
Median (95% Confidence Interval) [Months]	8.25	NA

10. Secondary Outcome

Title	Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD)
Description	Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Time Frame	Baseline until Disease Progression or Death Due to Any Cause (Up To 21 Months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
Arm/Group Description	Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Measure Participants	16	8
Number [Percentage of participants]	81.3 508.1%	87.5 1093.8%

11. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival is defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date for a particular analysis, overall survival duration was censored for that analysis at the date of last prior contact.
Time Frame	Baseline to Date of Death Due to Any Cause (Up To 21 Months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug. Number of participants censored were Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide = 9 and Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide = 6.

Arm/Group Title	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide	Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
Arm/Group Description	Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.	Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
Measure Participants	16	8
Median (95% Confidence Interval) [Months]	16.72	NA

Adverse Events

Time Frame	Up To 2 years
Adverse Event Reporting Description	All participants who received at least one dose of study drug. There are gender specific adverse events, occurring only in male or female participants. The number of participants exposed has been adjusted accordingly.
Arm/Group Title	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide		Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
Arm/Group Description	Participants received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥ 60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.		Participants received olaratumab 20 mg/kg loading dose on days 1, 8 of cycle 1. From cycle 2, they received olaratumab 15 mg/kg on days 1, 8 plus doxorubicin 25 mg/m^2 on days 1, 2, 3 plus ifosfamide 2.5 g/m^2 per day on days 1, 2, 3, 4 plus mesna dose ≥60% of ifosfamide dose on days 1, 2, 3 of a 21-day cycle for a maximum of 6 cycles, or until a discontinuation criterion was met. All treatments were administered intravenously.
All Cause Mortality
	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide		Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/16 (43.8%)		2/8 (25%)
Serious Adverse Events
	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide		Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/16 (56.3%)		7/8 (87.5%)
Blood and lymphatic system disorders
Anaemia	2/16 (12.5%)	5	1/8 (12.5%)	1
Febrile neutropenia	6/16 (37.5%)	8	4/8 (50%)	6
Neutropenia	1/16 (6.3%)	1	0/8 (0%)	0
Cardiac disorders
Atrial fibrillation	0/16 (0%)	0	1/8 (12.5%)	1
Gastrointestinal disorders
Haemorrhoids	1/16 (6.3%)	1	0/8 (0%)	0
Nausea	1/16 (6.3%)	1	0/8 (0%)	0
Oesophagitis	1/16 (6.3%)	1	0/8 (0%)	0
Vomiting	1/16 (6.3%)	1	0/8 (0%)	0
General disorders
Fatigue	2/16 (12.5%)	2	0/8 (0%)	0
Mucosal inflammation	1/16 (6.3%)	1	0/8 (0%)	0
Infections and infestations
Device related infection	1/16 (6.3%)	1	0/8 (0%)	0
Pneumonia	0/16 (0%)	0	2/8 (25%)	2
Injury, poisoning and procedural complications
Fracture	0/16 (0%)	0	1/8 (12.5%)	1
Investigations
Blood creatinine increased	0/16 (0%)	0	1/8 (12.5%)	1
Platelet count decreased	2/16 (12.5%)	2	2/8 (25%)	3
White blood cell count decreased	0/16 (0%)	0	1/8 (12.5%)	1
Metabolism and nutrition disorders
Dehydration	1/16 (6.3%)	1	0/8 (0%)	0
Hyponatraemia	1/16 (6.3%)	1	0/8 (0%)	0
Musculoskeletal and connective tissue disorders
Muscular weakness	1/16 (6.3%)	1	0/8 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic neoplasm	1/16 (6.3%)	1	0/8 (0%)	0
Tumour haemorrhage	1/16 (6.3%)	1	0/8 (0%)	0
Tumour pain	1/16 (6.3%)	1	0/8 (0%)	0
Product Issues
Device dislocation	0/16 (0%)	0	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/16 (6.3%)	1	0/8 (0%)	0
Vascular disorders
Haemodynamic instability	1/16 (6.3%)	1	0/8 (0%)	0
Hypotension	1/16 (6.3%)	1	0/8 (0%)	0
Other (Not Including Serious) Adverse Events
	Olaratumab 15 mg/kg + Doxorubicin + Ifosfamide		Olaratumab 20 mg/kg + Doxorubicin + Ifosfamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/16 (100%)		8/8 (100%)
Blood and lymphatic system disorders
Anaemia	11/16 (68.8%)	63	8/8 (100%)	33
Febrile neutropenia	2/16 (12.5%)	2	1/8 (12.5%)	1
Leukopenia	4/16 (25%)	5	3/8 (37.5%)	6
Lymphopenia	3/16 (18.8%)	8	2/8 (25%)	7
Neutropenia	9/16 (56.3%)	26	4/8 (50%)	7
Thrombocytopenia	5/16 (31.3%)	20	3/8 (37.5%)	13
Cardiac disorders
Angina pectoris	1/16 (6.3%)	1	0/8 (0%)	0
Palpitations	0/16 (0%)	0	1/8 (12.5%)	1
Tachycardia	2/16 (12.5%)	3	2/8 (25%)	3
Ear and labyrinth disorders
Tinnitus	2/16 (12.5%)	3	0/8 (0%)	0
Vertigo	1/16 (6.3%)	1	1/8 (12.5%)	2
Eye disorders
Dry eye	2/16 (12.5%)	3	0/8 (0%)	0
Eye swelling	1/16 (6.3%)	1	0/8 (0%)	0
Lacrimation increased	0/16 (0%)	0	1/8 (12.5%)	1
Photophobia	0/16 (0%)	0	1/8 (12.5%)	1
Xerophthalmia	0/16 (0%)	0	1/8 (12.5%)	1
Gastrointestinal disorders
Abdominal pain	2/16 (12.5%)	6	1/8 (12.5%)	1
Abdominal pain lower	1/16 (6.3%)	1	0/8 (0%)	0
Aphthous ulcer	1/16 (6.3%)	2	1/8 (12.5%)	1
Constipation	11/16 (68.8%)	26	3/8 (37.5%)	6
Diarrhoea	3/16 (18.8%)	5	1/8 (12.5%)	1
Dry mouth	1/16 (6.3%)	1	2/8 (25%)	2
Dyspepsia	2/16 (12.5%)	2	1/8 (12.5%)	1
Flatulence	2/16 (12.5%)	2	0/8 (0%)	0
Gastritis	1/16 (6.3%)	1	0/8 (0%)	0
Gastrooesophageal reflux disease	3/16 (18.8%)	4	0/8 (0%)	0
Gingival bleeding	0/16 (0%)	0	1/8 (12.5%)	1
Haemorrhoids	3/16 (18.8%)	3	0/8 (0%)	0
Nausea	14/16 (87.5%)	39	6/8 (75%)	16
Oral pain	0/16 (0%)	0	1/8 (12.5%)	1
Proctalgia	2/16 (12.5%)	6	0/8 (0%)	0
Rectal haemorrhage	2/16 (12.5%)	3	0/8 (0%)	0
Stomatitis	5/16 (31.3%)	15	0/8 (0%)	0
Toothache	1/16 (6.3%)	1	0/8 (0%)	0
Vomiting	6/16 (37.5%)	12	3/8 (37.5%)	4
General disorders
Asthenia	4/16 (25%)	8	0/8 (0%)	0
Catheter site pain	1/16 (6.3%)	1	0/8 (0%)	0
Chills	2/16 (12.5%)	2	0/8 (0%)	0
Fatigue	12/16 (75%)	22	6/8 (75%)	16
Mucosal inflammation	5/16 (31.3%)	5	1/8 (12.5%)	1
Oedema	1/16 (6.3%)	1	0/8 (0%)	0
Oedema peripheral	1/16 (6.3%)	1	0/8 (0%)	0
Pain	1/16 (6.3%)	1	0/8 (0%)	0
Pyrexia	2/16 (12.5%)	2	2/8 (25%)	2
Hepatobiliary disorders
Cholecystitis chronic	1/16 (6.3%)	1	0/8 (0%)	0
Infections and infestations
Abscess limb	1/16 (6.3%)	1	0/8 (0%)	0
Bone abscess	1/16 (6.3%)	1	0/8 (0%)	0
Candida infection	3/16 (18.8%)	3	0/8 (0%)	0
Conjunctivitis	1/16 (6.3%)	1	1/8 (12.5%)	3
Gastroenteritis	1/16 (6.3%)	1	0/8 (0%)	0
Influenza	1/16 (6.3%)	3	0/8 (0%)	0
Nasopharyngitis	3/16 (18.8%)	3	0/8 (0%)	0
Oral herpes	1/16 (6.3%)	1	0/8 (0%)	0
Rash pustular	1/16 (6.3%)	1	0/8 (0%)	0
Scrotal abscess	1/7 (14.3%)	3	0/3 (0%)	0
Skin infection	0/16 (0%)	0	2/8 (25%)	2
Upper respiratory tract infection	1/16 (6.3%)	1	0/8 (0%)	0
Urinary tract infection	1/16 (6.3%)	1	0/8 (0%)	0
Vulval abscess	1/9 (11.1%)	1	0/5 (0%)	0
Wound infection	1/16 (6.3%)	1	0/8 (0%)	0
Injury, poisoning and procedural complications
Animal bite	1/16 (6.3%)	1	0/8 (0%)	0
Infusion related reaction	3/16 (18.8%)	4	0/8 (0%)	0
Investigations
Activated partial thromboplastin time prolonged	0/16 (0%)	0	1/8 (12.5%)	1
Alanine aminotransferase increased	5/16 (31.3%)	9	3/8 (37.5%)	3
Aspartate aminotransferase increased	4/16 (25%)	5	1/8 (12.5%)	1
Blood alkaline phosphatase increased	3/16 (18.8%)	3	0/8 (0%)	0
Blood creatine increased	1/16 (6.3%)	1	0/8 (0%)	0
Blood creatinine increased	1/16 (6.3%)	1	2/8 (25%)	2
Electrocardiogram st segment depression	1/16 (6.3%)	1	0/8 (0%)	0
Electrocardiogram t wave amplitude decreased	1/16 (6.3%)	1	0/8 (0%)	0
Hormone level abnormal	1/16 (6.3%)	2	0/8 (0%)	0
Neutrophil count decreased	3/16 (18.8%)	4	1/8 (12.5%)	7
Platelet count decreased	1/16 (6.3%)	2	2/8 (25%)	15
Prothrombin time prolonged	0/16 (0%)	0	1/8 (12.5%)	1
White blood cell count decreased	2/16 (12.5%)	5	2/8 (25%)	10
Metabolism and nutrition disorders
Decreased appetite	3/16 (18.8%)	3	1/8 (12.5%)	1
Fluid retention	2/16 (12.5%)	7	0/8 (0%)	0
Hyperglycaemia	0/16 (0%)	0	4/8 (50%)	4
Hypoalbuminaemia	1/16 (6.3%)	1	0/8 (0%)	0
Hypocalcaemia	0/16 (0%)	0	2/8 (25%)	2
Hypokalaemia	5/16 (31.3%)	7	1/8 (12.5%)	1
Hyponatraemia	2/16 (12.5%)	2	1/8 (12.5%)	1
Hypophosphataemia	1/16 (6.3%)	2	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/16 (6.3%)	3	1/8 (12.5%)	1
Back pain	2/16 (12.5%)	2	0/8 (0%)	0
Bone pain	2/16 (12.5%)	3	0/8 (0%)	0
Mobility decreased	1/16 (6.3%)	1	0/8 (0%)	0
Muscle spasms	1/16 (6.3%)	2	0/8 (0%)	0
Musculoskeletal pain	1/16 (6.3%)	2	0/8 (0%)	0
Myalgia	2/16 (12.5%)	2	1/8 (12.5%)	2
Neck pain	2/16 (12.5%)	2	0/8 (0%)	0
Pain in extremity	1/16 (6.3%)	9	1/8 (12.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression	1/16 (6.3%)	1	0/8 (0%)	0
Tumour pain	1/16 (6.3%)	1	1/8 (12.5%)	1
Nervous system disorders
Dizziness	3/16 (18.8%)	3	2/8 (25%)	2
Headache	4/16 (25%)	6	1/8 (12.5%)	1
Myoclonus	0/16 (0%)	0	1/8 (12.5%)	1
Neurotoxicity	2/16 (12.5%)	3	0/8 (0%)	0
Paraesthesia	1/16 (6.3%)	1	2/8 (25%)	3
Paraparesis	1/16 (6.3%)	2	0/8 (0%)	0
Paresis	1/16 (6.3%)	1	0/8 (0%)	0
Restless legs syndrome	0/16 (0%)	0	1/8 (12.5%)	1
Syncope	3/16 (18.8%)	3	2/8 (25%)	2
Tension headache	0/16 (0%)	0	1/8 (12.5%)	1
Tremor	0/16 (0%)	0	1/8 (12.5%)	1
Product Issues
Device occlusion	1/16 (6.3%)	1	0/8 (0%)	0
Psychiatric disorders
Anxiety	2/16 (12.5%)	2	1/8 (12.5%)	1
Confusional state	2/16 (12.5%)	3	0/8 (0%)	0
Delirium	0/16 (0%)	0	1/8 (12.5%)	1
Depressed mood	0/16 (0%)	0	1/8 (12.5%)	1
Depression	1/16 (6.3%)	1	1/8 (12.5%)	1
Insomnia	1/16 (6.3%)	1	0/8 (0%)	0
Panic attack	0/16 (0%)	0	1/8 (12.5%)	1
Restlessness	0/16 (0%)	0	2/8 (25%)	3
Sleep disorder	0/16 (0%)	0	1/8 (12.5%)	1
Substance-induced psychotic disorder	0/16 (0%)	0	1/8 (12.5%)	1
Renal and urinary disorders
Bladder pain	1/16 (6.3%)	1	0/8 (0%)	0
Chronic kidney disease	0/16 (0%)	0	1/8 (12.5%)	1
Dysuria	1/16 (6.3%)	1	0/8 (0%)	0
Glycosuria	1/16 (6.3%)	2	0/8 (0%)	0
Urinary retention	1/16 (6.3%)	1	0/8 (0%)	0
Urinary tract disorder	1/16 (6.3%)	1	0/8 (0%)	0
Reproductive system and breast disorders
Vulvovaginal dryness	1/9 (11.1%)	1	0/5 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/16 (6.3%)	1	0/8 (0%)	0
Dyspnoea	2/16 (12.5%)	3	0/8 (0%)	0
Dyspnoea exertional	1/16 (6.3%)	2	0/8 (0%)	0
Epistaxis	1/16 (6.3%)	2	0/8 (0%)	0
Haemoptysis	1/16 (6.3%)	1	0/8 (0%)	0
Hiccups	3/16 (18.8%)	4	0/8 (0%)	0
Nasal congestion	0/16 (0%)	0	1/8 (12.5%)	1
Nasal dryness	1/16 (6.3%)	1	0/8 (0%)	0
Oropharyngeal pain	0/16 (0%)	0	3/8 (37.5%)	3
Respiratory symptom	1/16 (6.3%)	1	0/8 (0%)	0
Rhinorrhoea	0/16 (0%)	0	3/8 (37.5%)	3
Throat irritation	1/16 (6.3%)	1	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Alopecia	1/16 (6.3%)	1	0/8 (0%)	0
Dermatitis acneiform	0/16 (0%)	0	1/8 (12.5%)	1
Dry skin	1/16 (6.3%)	1	0/8 (0%)	0
Hyperhidrosis	0/16 (0%)	0	1/8 (12.5%)	1
Nail discolouration	1/16 (6.3%)	1	0/8 (0%)	0
Nail disorder	1/16 (6.3%)	3	1/8 (12.5%)	1
Night sweats	1/16 (6.3%)	1	1/8 (12.5%)	1
Palmar-plantar erythrodysaesthesia syndrome	2/16 (12.5%)	3	0/8 (0%)	0
Rash	0/16 (0%)	0	1/8 (12.5%)	1
Vascular disorders
Axillary vein thrombosis	1/16 (6.3%)	1	0/8 (0%)	0
Flushing	0/16 (0%)	0	1/8 (12.5%)	2
Hypertension	1/16 (6.3%)	1	0/8 (0%)	0
Hypotension	0/16 (0%)	0	1/8 (12.5%)	2
Venous thrombosis limb	1/16 (6.3%)	1	0/8 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.