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

NCT02659020 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: 15839I5B-MC-JGDL2015-001316-34
• Study Type: interventional
• Target: 310
• Locations: 10 countries
• Sites: 48

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

Outcome Measures

Primary Outcomes (2)

• Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT)

  A Dose Limiting Toxicity is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfils any one of the following criteria, graded according to the NCI-CTCAE Version 4.0: 1. Febrile neutropenia with documented Grade ≥3 infection or sepsis 2. Grade 4 neutropenia lasting 7 days or longer. 3. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by hemorrhage. 4. Nonhematologic Grade ≥3 toxicity, except for toxicities such as nausea, vomiting, transient electrolyte abnormalities, or diarrhoea that can be controlled with optimal medical management within 48 hours.

  Cycle 1 (Up To 21 Days)

• Phase 2: Overall Survival (OS) (Olaratumab-Naive)

  OS was defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date for a particular analysis, overall survival duration was censored for that analysis at the date of last prior contact.

  Baseline to Date of Death Due to Any Cause (Up To 38 Months)

Secondary Outcomes (17)

• Phase 1b: Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab

  Pre-dose, 5 minutes (min), 1, 4, 4.5, 24, 96, 168, 336 hours (h) post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1, Cycle 3 Day 8

• Phase 1b: PK: Minimum Serum Concentration (Cmin) of Olaratumab

  Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1

• Phase 1b: PK: Elimination Half-Life (T1/2) of Olaratumab

  Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1, Cycle 3 Day 8

• Phase 1b/2: PK: Cmax of Gemcitabine

  Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)

• Phase 1b/2: PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of Gemcitabine

  Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)

Study Arms (4)

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

EXPERIMENTAL

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.

Drug: Olaratumab; Drug: Gemcitabine; Drug: Docetaxel

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

EXPERIMENTAL

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).

Drug: Olaratumab; Drug: Gemcitabine; Drug: Docetaxel

Phase 2: Olaratumab + Gemcitabine + Docetaxel

EXPERIMENTAL

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.

Drug: Olaratumab; Drug: Gemcitabine; Drug: Docetaxel

Phase 2: Placebo + Gemcitabine + Docetaxel

PLACEBO COMPARATOR

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.

Drug: Gemcitabine; Drug: Docetaxel; Drug: Placebo

Interventions

Olaratumab DRUG

Administered IV

Also known as: LY3012207, IMC-3G3

Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel; Phase 1b: Cohort 2 overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel; Phase 2: Olaratumab + Gemcitabine + Docetaxel

Gemcitabine DRUG

Administered IV

Also known as: LY188011, Gemzar

Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel; Phase 1b: Cohort 2 overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel; Phase 2: Olaratumab + Gemcitabine + Docetaxel; Phase 2: Placebo + Gemcitabine + Docetaxel

Docetaxel DRUG

Administered IV

Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel; Phase 1b: Cohort 2 overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel; Phase 2: Olaratumab + Gemcitabine + Docetaxel; Phase 2: Placebo + Gemcitabine + Docetaxel

Placebo DRUG

Administered IV

Phase 2: Placebo + Gemcitabine + Docetaxel

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (48)

UCLA Medical Center

Santa Monica, California, 90404, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Mayo Clinic-Jacksonville

Jacksonville, Florida, 32224, United States

Location

Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Georgia Cancer Specialists PC

Atlanta, Georgia, 30342, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University Medical School

St Louis, Missouri, 63110, United States

Location

Nebraska Methodist Cancer Center

Omaha, Nebraska, 68114, United States

Location

Monter Cancer Center

Lake Success, New York, 11042, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Oklahoma Cancer Specialists & Research Institute, LLC

Tulsa, Oklahoma, 74146, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111-2497, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-6307, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Klinikum der Universität München

München, Bavaria, 81377, Germany

Location

Universitätsklinikum Regensburg

Regensburg, Bavaria, 93053, Germany

Location

Helios Klinikum Bad Saarow

Bad Saarow, Brandenburg, 15526, Germany

Location

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

Location

HELIOS Klinikum Berlin-Buch

Berlin, 13125, Germany

Location

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz

Szolnok, 5000, Hungary

Location

Sheba Medical Center

Tel Litwinsky, Ramat Gan, 5265601, Israel

Location

Rambam Medical Center

Haifa, 3525408, Israel

Location

Rabin Medical Center

Petah Tikva, 4941492, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

Fondazione Piemonte l'Oncologia-Istituto Ricerca Cura Cancro

Candiolo, Torino, 10060, Italy

Location

Humanitas Gradenigo

Torino, 10153, Italy

Location

Centrum Onkologii-Instytut im Marii Sklodowskiej-Curie

Warsaw, 02-781, Poland

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

University College Hospital - London

London, Greater London, NW1 2BU, United Kingdom

Location

Royal Marsden NHS Trust

London, Greater London, SW3 6JJ, United Kingdom

Location

Clatterbridge Cancer Centre

Bebbington, Merseyside, CH63 4JY, United Kingdom

Location

Western General Hospital

Edinburgh, Scotland, EH4 2XU, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Sarcoma

Interventions

olaratumab; Gemcitabine; Docetaxel

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2016
• First Posted: January 20, 2016
• Study Start: March 1, 2016
• Primary Completion: July 28, 2020
• Study Completion: April 27, 2021
• Last Updated: May 9, 2022
• Results First Posted: October 11, 2021

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

DE (6); IT (2); PL (1); ES (4); HU (1); AU (2); GB (4); FR (3); US (21); IL (4)