A Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma

ID: NCT02659020
Status: Recruiting
Phase: Phase 1/Phase 2
Start Date: March 01, 2016
First Submitted: January 15, 2016
Last Updated: February 23, 2018
Results: N/A
Organization: Eli Lilly and Company
Sponsors & Collaborators: Eli Lilly and Company
Location: Australia, France, Germany, Hungary, Israel, Italy, Poland, Spain, United Kingdom, United States
Conditions: Soft Tissue Sarcoma
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Study Description

Brief Summary

The main purpose of this study is to evaluate the safety and efficacy of two anti-cancer drugs (gemcitabine and docetaxel) with and without the study drug known as olaratumab in participants with advanced soft tissue sarcoma (STS) or STS that has spread to another part(s) of the body.

Detailed Description

Condition or disease Intervention/treatment Phase

Soft Tissue Sarcoma

Drug: Olaratumab
Other Names
LY3012207 IMC-3G3
Drug: Gemcitabine
Other Names
LY188011 Gemzar
Drug: Docetaxel
Other Names
Drug: Placebo
Other Names
Phase 1/Phase 2

Tracking Information

First Submitted DateJanuary 15, 2016
Last Update Posted DateFebruary 23, 2018
Start DateMarch 01, 2016
Anticipated Completion DateDecember 01, 2020
Primary Completion DateDecember 01, 2019
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Phase 2: Overall Survival (OS) (Olaratumab-Naive) [Time Frame: Baseline to Date of Death Due to Any Cause (Approximately 38 Months)]

  • Phase 1b: Recommended Phase 2 Dose of Olaratumab: Number of Participants with Dose Limiting Toxicity (DLT) [Time Frame: Cycle 1 (21 Days)]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab [Time Frame: Post-dose on Days 1 and 8 of Cycles 1 and 3 (21 day cycles)]

  • PK: Minimum Serum Concentration (Cmin) of Olaratumab [Time Frame: Pre-dose on Day 8 of Cycles 1 and 3, and on Day 1 of Cycles 2 and 4]

  • PK: Elimination Half-Life (T1/2) of Olaratumab [Time Frame: Days 8 to 21 of Cycles 1 and 3]

  • PK: Cmax of Gemcitabine [Time Frame: Post-Dose on Day 8 of Cycle 1]

  • PK: Area Under the Concentration-Time Curve (AUC) of Gemcitabine [Time Frame: Day 8 of Cycle 1, Immediately Post-Dose up to 24 Hours Post-Dose]

  • PK: Cmax of Docetaxel [Time Frame: Post-Dose on Day 8 of Cycle 1]

  • PK: AUC of Docetaxel [Time Frame: Day 8 of Cycle 1, Immediately Post-Dose up to 48 Hours Post-Dose]

  • OS (Olaratumab-Pre-Treated) [Time Frame: Baseline to Date of Death Due to Any Cause (Approximately 38 Months)]

  • Progression Free Survival (PFS) [Time Frame: Baseline to Objective Progression or Death from Any Cause (Approximately 38 Months)]

  • Proportion of Participants With a Complete or Partial Response (Objective Response Rate [ORR]) [Time Frame: Baseline to Objective Progression or Start of New Anti-Cancer Therapy (Approximately 38 Months)]

  • Disease Control Rate (DCR): Defined as Proportion of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) [Time Frame: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Approximately 38 Months)]

  • Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score" [Time Frame: Baseline through Follow-up (Approximately 6 Months)]

  • Time to Sustained Worsening of Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Scores [Time Frame: Baseline through Follow-up (Approximately 38 Months)]

  • Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L) [Time Frame: Baseline through Follow-up (Approximately 38 Months)]

  • Number of Participants with Anti-Olaratumab Antibodies [Time Frame: Baseline through Follow-Up (Approximately 38 Months]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleA Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma
Official TitleA Phase 1b (Open-Label) / Phase 2 (Randomized, Double-Blinded) Study Evaluating Gemcitabine and Docetaxel With or Without Olaratumab in the Treatment of Advanced Soft Tissue Sarcoma
Brief Summary

The main purpose of this study is to evaluate the safety and efficacy of two anti-cancer drugs (gemcitabine and docetaxel) with and without the study drug known as olaratumab in participants with advanced soft tissue sarcoma (STS) or STS that has spread to another part(s) of the body.

Detailed Description

Study TypeInterventional
Study PhasePhase 1/Phase 2
Estimated Enrollment
310
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Double
Primary Purpose
Treatment
Conditions
Soft Tissue Sarcoma
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Olaratumab

Administered IV

Other Names
LY3012207
IMC-3G3
Drug: Gemcitabine

Administered IV

Other Names
LY188011
Gemzar
Drug: Docetaxel

Administered IV

Other Names
Drug: Placebo

Administered IV

Other Names
Study Groups/Cohorts
Olaratumab + Gemcitabine + Docetaxel (Dose Escalation)
Olaratumab intravenously (IV) on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.

Olaratumab + Gemcitabine + Docetaxel
Olaratumab IV on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.

Placebo + Gemcitabine + Docetaxel
Placebo IV on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.

Study Arms
Experimental Olaratumab + Gemcitabine + Docetaxel
Olaratumab IV on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Olaratumab
Administered IV

Experimental Olaratumab + Gemcitabine + Docetaxel
Olaratumab IV on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Gemcitabine
Administered IV

Experimental Olaratumab + Gemcitabine + Docetaxel
Olaratumab IV on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Docetaxel
Administered IV

Experimental Olaratumab + Gemcitabine + Docetaxel (Dose Escalation)
Olaratumab intravenously (IV) on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Olaratumab
Administered IV

Experimental Olaratumab + Gemcitabine + Docetaxel (Dose Escalation)
Olaratumab intravenously (IV) on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Docetaxel
Administered IV

Experimental Olaratumab + Gemcitabine + Docetaxel (Dose Escalation)
Olaratumab intravenously (IV) on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Gemcitabine
Administered IV

Placebo Comparator Placebo + Gemcitabine + Docetaxel
Placebo IV on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Gemcitabine
Administered IV

Placebo Comparator Placebo + Gemcitabine + Docetaxel
Placebo IV on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Docetaxel
Administered IV

Placebo Comparator Placebo + Gemcitabine + Docetaxel
Placebo IV on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Placebo
Administered IV

Arm Intervention/Treatment
Experimental Olaratumab + Gemcitabine + Docetaxel
Olaratumab IV on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Olaratumab
Experimental Olaratumab + Gemcitabine + Docetaxel
Olaratumab IV on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Gemcitabine
Experimental Olaratumab + Gemcitabine + Docetaxel
Olaratumab IV on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Docetaxel
Experimental Olaratumab + Gemcitabine + Docetaxel (Dose Escalation)
Olaratumab intravenously (IV) on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Olaratumab
Experimental Olaratumab + Gemcitabine + Docetaxel (Dose Escalation)
Olaratumab intravenously (IV) on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Docetaxel
Experimental Olaratumab + Gemcitabine + Docetaxel (Dose Escalation)
Olaratumab intravenously (IV) on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Gemcitabine
Placebo Comparator Placebo + Gemcitabine + Docetaxel
Placebo IV on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Gemcitabine
Placebo Comparator Placebo + Gemcitabine + Docetaxel
Placebo IV on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Docetaxel
Placebo Comparator Placebo + Gemcitabine + Docetaxel
Placebo IV on day 1 and day 8 of each cycle (1 cycle = 21 days) with gemcitabine IV on day 1 and 8 and docetaxel IV on day 8. Participants may continue to receive treatment until discontinuation criteria are met.
Drug : Placebo

Recruitment Information

Recruitment Status:Recruiting
Enrollment310
Completion DateDecember 01, 2020
Eligibility Criteria: Inclusion Criteria:
- The participant may have no more than 2 prior lines of systemic therapies (neoadjuvant and adjuvant therapies will not be considered as a prior line of therapy) for advanced or metastatic disease and is suitable to receive gemcitabine and docetaxel therapy. All previous therapies must have completed ≥ 3 weeks (21 days) prior to first dose of study drug.
- In the Phase 2 part, prior olaratumab/doxorubicin combination therapy in 1 prior treatment line is allowed.
- Prior olaratumab therapy must have been received with doxorubicin as indicated on the olaratumab label.
- Prior olaratumab therapy must have included at least 2 full cycles of olaratumab/doxorubicin (that is, a minimum of 4 doses of olaratumab).
- Participants, who completed at least 2 cycles of combination olaratumab/doxorubicin therapy then discontinued doxorubicin due to toxicity or maximum dosing and proceeded to olaratumab monotherapy, are eligible.
- The most recent dose of olaratumab must have been received within 180 days of randomization in this study.
- Availability of tumor tissue is mandatory for study eligibility. The participant must have consented to provide archived formalin-fixed paraffin-embedded 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).
- The participant has adequate hematologic, organ, and coagulation function within 2 weeks (14 days) prior to enrollment (Phase 1b) or randomization (Phase 2).

Exclusion Criteria:
- The participant is diagnosed with gastrointestinal stromal tumor (GIST) or Kaposi sarcoma.
- The participant has active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of enrollment (Phase 1b) or randomization (Phase 2). 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 enrollment (Phase 1b) /randomization (Phase 2) to rule out brain metastasis.
- The participant has received prior treatment with gemcitabine or docetaxel. Note: Participants previously enrolled in the I5B-MC-JGDJ (NCT02451943) or any other blinded study with olaratumab are not eligible to participate in this trial.
- The participant has electively planned or will require major surgery during the course of the study.
- Females who are pregnant or breastfeeding.
- The participant has an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required).
GenderAll
Age16 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Australia
France
Germany
Hungary
Israel
Italy
Poland
Spain
United Kingdom
United States

Administrative Information

NCT Number:NCT02659020
Other Study ID Numbers
15839
I5B-MC-JGDL
2015-001316-34
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Eli Lilly and Company
Collaborators
Not Available
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