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A Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma (ANNOUNCE 2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02659020
Recruitment Status : Active, not recruiting
First Posted : January 20, 2016
Last Update Posted : December 3, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE January 15, 2016
First Posted Date  ICMJE January 20, 2016
Last Update Posted Date December 3, 2019
Actual Study Start Date  ICMJE March 2, 2016
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 21, 2018)
  • Phase 1b: Recommended Phase 2 Dose of Olaratumab: Number of Participants with Dose Limiting Toxicity (DLT) [ Time Frame: Cycle 1 (21 Days) ]
  • Phase 2: Overall Survival (OS) (Olaratumab-Naive) [ Time Frame: Baseline to Date of Death Due to Any Cause (Approximately 38 Months) ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 15, 2016)
  • Recommended Phase 2 Dose of Olaratumab: Number of Participants with Dose Limiting Toxicity (DLT) [ Time Frame: Cycle 1 (21 Days) ]
  • Overall Survival (OS) [ Time Frame: Baseline to Date of Death Due to Any Cause (Approximately 15 Months) ]
Change History Complete list of historical versions of study NCT02659020 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2017)
  • 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  ICMJE
 (submitted: January 15, 2016)
  • 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 ]
  • Progression Free Survival (PFS) [ Time Frame: Baseline to Objective Progression or Death from Any Cause (Approximately 6 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 6 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 6 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 6 Months) ]
  • Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L) [ Time Frame: Baseline through Follow-up (Approximately 6 Months) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma
Official Title  ICMJE A 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 Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Soft Tissue Sarcoma
Intervention  ICMJE
  • Drug: Olaratumab
    Administered IV
    Other Names:
    • LY3012207
    • IMC-3G3
  • Drug: Gemcitabine
    Administered IV
    Other Names:
    • LY188011
    • Gemzar
  • Drug: Docetaxel
    Administered IV
  • Drug: Placebo
    Administered IV
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Olaratumab
    • Drug: Gemcitabine
    • Drug: Docetaxel
  • 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.
    Interventions:
    • Drug: Olaratumab
    • Drug: Gemcitabine
    • 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.
    Interventions:
    • Drug: Gemcitabine
    • Drug: Docetaxel
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: November 21, 2018)
310
Original Estimated Enrollment  ICMJE
 (submitted: January 15, 2016)
196
Estimated Study Completion Date  ICMJE December 1, 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   France,   Germany,   Hungary,   Israel,   Italy,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02659020
Other Study ID Numbers  ICMJE 15839
I5B-MC-JGDL ( Other Identifier: Eli Lilly and Company )
2015-001316-34 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Eli Lilly and Company
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP