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

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ClinicalTrials.gov Identifier: NCT02659020
Recruitment Status : Active, not recruiting
First Posted : January 20, 2016
Last Update Posted : November 19, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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.

Condition or disease Intervention/treatment Phase
Soft Tissue Sarcoma Drug: Olaratumab Drug: Gemcitabine Drug: Docetaxel Drug: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 310 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : March 2, 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 1, 2020


Arm Intervention/treatment
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.
Drug: Olaratumab
Administered IV
Other Names:
  • LY3012207
  • IMC-3G3

Drug: Gemcitabine
Administered IV
Other Names:
  • LY188011
  • Gemzar

Drug: Docetaxel
Administered IV

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.
Drug: Olaratumab
Administered IV
Other Names:
  • LY3012207
  • IMC-3G3

Drug: Gemcitabine
Administered IV
Other Names:
  • LY188011
  • Gemzar

Drug: Docetaxel
Administered IV

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.
Drug: Gemcitabine
Administered IV
Other Names:
  • LY188011
  • Gemzar

Drug: Docetaxel
Administered IV

Drug: Placebo
Administered IV




Primary Outcome Measures :
  1. Phase 1b: Recommended Phase 2 Dose of Olaratumab: Number of Participants with Dose Limiting Toxicity (DLT) [ Time Frame: Cycle 1 (21 Days) ]
  2. Phase 2: Overall Survival (OS) (Olaratumab-Naive) [ Time Frame: Baseline to Date of Death Due to Any Cause (Approximately 38 Months) ]

Secondary Outcome Measures :
  1. 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) ]
  2. 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 ]
  3. PK: Elimination Half-Life (T1/2) of Olaratumab [ Time Frame: Days 8 to 21 of Cycles 1 and 3 ]
  4. PK: Cmax of Gemcitabine [ Time Frame: Post-Dose on Day 8 of Cycle 1 ]
  5. 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 ]
  6. PK: Cmax of Docetaxel [ Time Frame: Post-Dose on Day 8 of Cycle 1 ]
  7. PK: AUC of Docetaxel [ Time Frame: Day 8 of Cycle 1, Immediately Post-Dose up to 48 Hours Post-Dose ]
  8. OS (Olaratumab-Pre-Treated) [ Time Frame: Baseline to Date of Death Due to Any Cause (Approximately 38 Months) ]
  9. Progression Free Survival (PFS) [ Time Frame: Baseline to Objective Progression or Death from Any Cause (Approximately 38 Months) ]
  10. 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) ]
  11. 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) ]
  12. 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) ]
  13. 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) ]
  14. Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L) [ Time Frame: Baseline through Follow-up (Approximately 38 Months) ]
  15. Number of Participants with Anti-Olaratumab Antibodies [ Time Frame: Baseline through Follow-Up (Approximately 38 Months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02659020


  Hide Study Locations
Locations
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United States, California
UCLA Medical Center
Santa Monica, California, United States, 90404
United States, Colorado
University of Colorado Cancer Center
Aurora, Colorado, United States, 80045
United States, Florida
Mayo Clinic-Jacksonville
Jacksonville, Florida, United States, 32224
Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
United States, Georgia
Georgia Cancer Specialists PC
Atlanta, Georgia, United States, 30342
United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University Medical School
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Nebraska Methodist Cancer Center
Omaha, Nebraska, United States, 68114
United States, New York
Monter Cancer Center
Lake Success, New York, United States, 11042
Columbia University Medical Center
New York, New York, United States, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Oklahoma
Oklahoma Cancer Specialists & Research Institute, LLC
Tulsa, Oklahoma, United States, 74146
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111-2497
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-6307
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Utah Cancer Specialists
Salt Lake City, Utah, United States, 84106
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia, 3000
France
Institut Bergonie
Bordeaux, France, 33076
Centre Oscar Lambret
Lille Cedex, France, 59020
Gustave Roussy
Villejuif Cedex, France, 94805
Germany
Universitätsklinikum Ulm
Ulm, Baden-Württemberg, Germany, 89081
Klinikum der Universität München
München, Bayern, Germany, 81377
Universitätsklinikum Regensburg
Regensburg, Bayern, Germany, 93053
Helios Klinikum Bad Saarow
Bad Saarow, Brandenburg, Germany, 15526
Medizinische Hochschule Hannover
Hannover, Niedersachsen, Germany, 30625
HELIOS Klinikum Berlin-Buch
Berlin, Germany, 13125
Hungary
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz
Szolnok, Hungary, 5000
Israel
Sheba Medical Center
Tel Hashomer, Ramat Gan, Israel, 5265601
Rambam Medical Center
Haifa, Israel, 3525408
Rabin Medical Center
Petah Tiqva, Israel, 4941492
Tel Aviv Sourasky Medical Center
Tel Aviv, Israel, 6423906
Italy
Fondazione Piemonte l'Oncologia-Istituto Ricerca Cura Cancro
Candiolo, Torino, Italy, 10060
Humanitas Gradenigo
Torino, Italy, 10153
Poland
Centrum Onkologii-Instytut im Marii Sklodowskiej-Curie
Warszawa, Poland, 02-781
Spain
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 08035
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Hospital Universitario La Paz
Madrid, Spain, 28046
Hospital Universitario Virgen del Rocio
Sevilla, Spain, 41013
United Kingdom
University College Hospital - London
London, Greater London, United Kingdom, NW1 2BU
Royal Marsden NHS Trust
London, Greater London, United Kingdom, SW3 6JJ
Clatterbridge Cancer Centre
Bebbington, Merseyside, United Kingdom, CH63 4JY
Western General Hospital
Edinburgh, Scotland, United Kingdom, EH4 2XU
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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

Additional Information:
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02659020     History of Changes
Other Study ID Numbers: 15839
I5B-MC-JGDL ( Other Identifier: Eli Lilly and Company )
2015-001316-34 ( EudraCT Number )
First Posted: January 20, 2016    Key Record Dates
Last Update Posted: November 19, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Additional relevant MeSH terms:
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Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Docetaxel
Olaratumab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators