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

Lilly

Status and phase: Completed; Phase 2; Phase 1

Conditions: Soft Tissue Sarcoma

Treatments: Drug: Olaratumab; Drug: Docetaxel; Drug: Placebo; Drug: Gemcitabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02659020

I5B-MC-JGDL (Other Identifier)

15839

2015-001316-34 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 310 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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310 participants in 4 patient groups, including a placebo group

Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel

Experimental group

Description:

Participants received intravenous infusions of olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m\^2) on days 1, 8 plus docetaxel 75 mg/m\^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.

Treatment:

Drug: Gemcitabine

Drug: Olaratumab

Drug: Docetaxel

Phase 1b: Cohort 2 overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel

Experimental group

Description:

Participants received intravenous infusions of olaratumab 20 mg/kg on days 1, 8 in combination with gemcitabine 900 mg/m\^2 on days 1, 8 and docetaxel 75 mg/m\^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met (cohort 2). Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2 (cohort 2 expansion).

Treatment:

Drug: Gemcitabine

Drug: Olaratumab

Drug: Docetaxel

Phase 2: Olaratumab + Gemcitabine + Docetaxel

Experimental group

Description:

Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m\^2 on days 1, 8 and docetaxel 75 mg/m\^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort is a combination of participants who never received olaratumab (olaratumab-naive) and who received commercially available olaratumab (olaratumab pre-treated) prior to enrollment.

Treatment:

Drug: Gemcitabine

Drug: Olaratumab

Drug: Docetaxel

Phase 2: Placebo + Gemcitabine + Docetaxel

Placebo Comparator group

Description:

Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m\^2 on days 1, 8 and docetaxel 75 mg/m\^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort is a combination of participants who never received olaratumab (olaratumab-naive) and who received commercially available olaratumab (olaratumab pre-treated) prior to enrollment.

Treatment:

Drug: Gemcitabine

Drug: Placebo

Drug: Docetaxel