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

NCT ID: NCT02659020

Last Updated: 2022-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 310 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-01
• Study Completion Date: 2021-04-27

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.

Conditions

Soft Tissue Sarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Olaratumab

Intervention Type: DRUG

Administered IV

Gemcitabine

Intervention Type: DRUG

Administered IV

Docetaxel

Intervention Type: DRUG

Administered IV

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

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).

Group Type: EXPERIMENTAL

Olaratumab

Intervention Type: DRUG

Administered IV

Gemcitabine

Intervention Type: DRUG

Administered IV

Docetaxel

Intervention Type: DRUG

Administered IV

Phase 2: Olaratumab + Gemcitabine + Docetaxel

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.

Group Type: EXPERIMENTAL

Olaratumab

Intervention Type: DRUG

Administered IV

Gemcitabine

Intervention Type: DRUG

Administered IV

Docetaxel

Intervention Type: DRUG

Administered IV

Phase 2: Placebo + Gemcitabine + Docetaxel

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.

Group Type: PLACEBO_COMPARATOR

Gemcitabine

Intervention Type: DRUG

Administered IV

Docetaxel

Intervention Type: DRUG

Administered IV

Placebo

Intervention Type: DRUG

Administered IV

Interventions

Olaratumab

Administered IV

Intervention Type: DRUG

Gemcitabine

Administered IV

Intervention Type: DRUG

Docetaxel

Administered IV

Intervention Type: DRUG

Placebo

Administered IV

Intervention Type: DRUG

Other Intervention Names

LY3012207; IMC-3G3; LY188011; Gemzar

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).

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

UCLA Medical Center

Santa Monica, California, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

Mayo Clinic-Jacksonville

Jacksonville, Florida, United States

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Georgia Cancer Specialists PC

Atlanta, Georgia, United States

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Washington University Medical School

St Louis, Missouri, United States

Nebraska Methodist Cancer Center

Omaha, Nebraska, United States

Monter Cancer Center

Lake Success, New York, United States

Columbia University Medical Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Ohio State University Medical Center

Columbus, Ohio, United States

Oklahoma Cancer Specialists & Research Institute, LLC

Tulsa, Oklahoma, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Utah Cancer Specialists

Salt Lake City, Utah, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Institut Bergonie

Bordeaux, , France

Centre Oscar Lambret

Lille, , France

Gustave Roussy

Villejuif, , France

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Klinikum der Universität München

München, Bavaria, Germany

Universitätsklinikum Regensburg

Regensburg, Bavaria, Germany

Helios Klinikum Bad Saarow

Bad Saarow, Brandenburg, Germany

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

HELIOS Klinikum Berlin-Buch

Berlin, , Germany

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz

Szolnok, , Hungary

Sheba Medical Center

Tel Litwinsky, Ramat Gan, Israel

Rambam Medical Center

Haifa, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Fondazione Piemonte l'Oncologia-Istituto Ricerca Cura Cancro

Candiolo, Torino, Italy

Humanitas Gradenigo

Torino, , Italy

Centrum Onkologii-Instytut im Marii Sklodowskiej-Curie

Warsaw, , Poland

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

University College Hospital - London

London, Greater London, United Kingdom

Royal Marsden NHS Trust

London, Greater London, United Kingdom

Clatterbridge Cancer Centre

Bebbington, Merseyside, United Kingdom

Western General Hospital

Edinburgh, Scotland, United Kingdom

Countries

United States; Australia; France; Germany; Hungary; Israel; Italy; Poland; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://trials.lillytrialguide.com/en-US/trial/3Jz0lQ8yUE2Q42EWCOQKWq

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

Other Identifiers

I5B-MC-JGDL

Identifier Type: OTHER

Identifier Source: secondary_id

2015-001316-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

15839

Identifier Type: -

Identifier Source: org_study_id