Clinical Trials /

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

NCT02659020

Description:

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.

Related Conditions:
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 15839
  • SECONDARY ID: I5B-MC-JGDL
  • SECONDARY ID: 2015-001316-34
  • NCT ID: NCT02659020

Conditions

  • Soft Tissue Sarcoma

Interventions

DrugSynonymsArms
OlaratumabLY3012207, IMC-3G3Olaratumab + Gemcitabine + Docetaxel (Dose Escalation)
GemcitabineLY188011, GemzarOlaratumab + Gemcitabine + Docetaxel (Dose Escalation)
DocetaxelOlaratumab + Gemcitabine + Docetaxel (Dose Escalation)
PlaceboPlacebo + Gemcitabine + Docetaxel

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Olaratumab + Gemcitabine + Docetaxel (Dose Escalation)ExperimentalOlaratumab 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 + Gemcitabine + DocetaxelExperimentalOlaratumab 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
Placebo + Gemcitabine + DocetaxelPlacebo ComparatorPlacebo 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.
  • Gemcitabine
  • Docetaxel
  • Placebo

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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:16 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1b: Recommended Phase 2 Dose of Olaratumab: Number of Participants with Dose Limiting Toxicity (DLT)
Time Frame:Cycle 1 (21 Days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:PK: Elimination Half-Life (T1/2) of Olaratumab
Time Frame:Days 8 to 21 of Cycles 1 and 3
Safety Issue:
Description:
Measure:PK: Cmax of Gemcitabine
Time Frame:Post-Dose on Day 8 of Cycle 1
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:PK: Cmax of Docetaxel
Time Frame:Post-Dose on Day 8 of Cycle 1
Safety Issue:
Description:
Measure:PK: AUC of Docetaxel
Time Frame:Day 8 of Cycle 1, Immediately Post-Dose up to 48 Hours Post-Dose
Safety Issue:
Description:
Measure:OS (Olaratumab-Pre-Treated)
Time Frame:Baseline to Date of Death Due to Any Cause (Approximately 38 Months)
Safety Issue:
Description:
Measure:Progression Free Survival (PFS)
Time Frame:Baseline to Objective Progression or Death from Any Cause (Approximately 38 Months)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L)
Time Frame:Baseline through Follow-up (Approximately 38 Months)
Safety Issue:
Description:
Measure:Number of Participants with Anti-Olaratumab Antibodies
Time Frame:Baseline through Follow-Up (Approximately 38 Months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eli Lilly and Company

Last Updated

August 25, 2017