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

• Register: ClinicalTrials.gov
• Last refreshed on: 29 April 2024
• Main ID: NCT02451943
• Date of registration: 20/05/2015
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: A Study of Doxorubicin Plus Olaratumab (LY3012207) in Participants With Advanced or Metastatic Soft Tissue Sarcoma ANNOUNCE
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Doxorubicin Plus Olaratumab Versus Doxorubicin Plus Placebo in Patients With Advanced or Metastatic Soft Tissue Sarcoma
• Date of first enrolment: September 14, 2015
• Target sample size: 509
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02451943
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Russian Federation, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: 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)
• Affiliation: Eli Lilly and Company

Key inclusion & exclusion criteria

Inclusion Criteria:

- Histologically confirmed diagnosis of advanced unresectable or metastatic soft tissue
sarcoma not amenable to curative treatment with surgery or radiotherapy. Participants
with Kaposi's sarcoma and gastrointestinal stromal tumors (GIST) will be excluded.
Note: Evidence of disease progression is required for participants that are not newly
diagnosed.

- Presence of measurable or nonmeasurable but evaluable disease as defined by the
Response Evaluation Criteria in Solid Tumors (RECIST 1.1, Eisenhauer et al. 2009).

- Performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.

- The participant has not received any previous treatment with anthracyclines.

- The participant may have had any number of prior systemic cytotoxic therapies for
advanced/metastatic disease and are considered appropriate candidates for
anthracycline therapy. All previous anticancer treatments must be completed = 3 weeks
(21 days) prior to first dose of study drug.

- Availability of tumor tissue is required for study eligibility. The participant must
have consented to provide archived formalin-fixed paraffin embedded (FFPE) tumor
tissue or be subject to a pre-treatment re-biopsy of primary or metastatic tumor
tissue for future central pathology review and translational research (if archived
tissue is unavailable).

- Adequate hematologic, organ, and coagulation within 2 weeks (14 days) prior to
randomization.

- Left ventricular ejection fraction (LVEF) =50% assessed within 28 days prior to
randomization.

- Females of child-bearing potential must have a negative serum pregnancy test within 7
days prior to randomization.

- Females of child-bearing potential and males must agree to use highly effective
contraceptive precautions during the trial and up to 3 months following the last dose
of study drug.

- The participant has, in the opinion of the investigator, a life expectancy of at least
3 months.

Exclusion Criteria:

- Diagnosis of GIST or Kaposi sarcoma.

- Active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at
the time of randomization. Participants with a history of a CNS metastasis previously
treated with curative intent (for example, stereotactic radiation or surgery) that
have 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 randomization to rule out brain metastasis.

- Prior treatment with doxorubicin, epirubicin, idarubicin, and/or other anthracyclines
or anthracenediones; the participant has received treatment with olaratumab or has
participated in a prior olaratumab trial.

- Prior radiotherapy of the mediastinal/pericardial area or whole pelvis radiation.

- The participant has symptomatic congestive heart failure (CHF), left ventricular
dysfunction (LVEF < 50%), severe myocardial insufficiency, cardiac arrhythmia, or
cardiomyopathy.

- The participant has unstable angina pectoris, angioplasty, cardiac stenting, or
myocardial infarction within 6 months of randomization.

- The participant has a QT interval calculated using Bazett's formula (QTcB) interval of
>450 milliseconds (msec) for males and >470 msec for females on screening
electrocardiogram (ECG).

- Females who are pregnant or breastfeeding.

- Known allergy to any of the treatment components including a history of allergic
reactions attributed to compounds of chemical or biological composition similar to
olaratumab.

- The participant has a known active fungal, bacterial, or viral infection including
human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not
required).



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Soft Tissue Sarcoma

Intervention(s)

Drug: Placebo

Drug: Doxorubicin

Drug: Olaratumab

Primary Outcome(s)

Overall Survival (OS) Leiomyosarcoma (LMS) [Time Frame: Randomization to Date of Death Due to Any Cause (Up to 35.8 Months)]

Overall Survival (OS) [Time Frame: Randomization to Date of Death Due to Any Cause (Up to 35.8 Months)]

Secondary Outcome(s)

Duration of Overall Response (DoR) [Time Frame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 33.4 Months)]

Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR) [Time Frame: Randomization to Objective Disease Progression or Death Due to Any Cause (Up to 45 Months)]

Change From Baseline to Maximum Improvement in Health Status Index Score on the EuroQol 5-Dimension 5-Level (EQ-5D-5L) [Time Frame: Randomization through Follow-up (Up to 35.8 Months)]

Progression Free Survival (PFS) [Time Frame: Randomization to Objective Progression or Death Due to Any Cause (Up to 35.8 Months)]

Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score" [Time Frame: Randomization through Follow-up (Up to 34.5 Months)]

Duration of Disease Control (DDC) [Time Frame: Date of CR, PR, or SD to Objective Disease Progression or Death Due to Any Cause (Up to 35.8 Months)]

PK: Volume of Distribution at Steady State (Vss) of Olaratumab: Mean Parameter Estimate [Time Frame: Cycle 1- 9: Day 1 and 8; Predose, 5 Minutes Post dose and then every other cycle and follow-up (30 Days)]

Time to First Worsening on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores [Time Frame: Randomization (Cycle 1) through Follow-up (Up to 35.8 Months)]

Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR) [Time Frame: Randomization to Objective Disease Progression or Death Due to Any Cause (Up to 35.8 Months)]

Pharmacokinetics (PK) Clearance of Olaratumab Mean Parameter Estimate [Time Frame: Cycle 1- 9: Day 1 and 8, Predose, 5 minutes Post dose and then every other cycle and follow-up (30 Days)]

Secondary ID(s)

2015-000134-30

15677

I5B-MC-JGDJ

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 17/12/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02451943