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Soft Tissue SarcomaPhase 1/2ANNOUNCE 2NCT02659020

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

A Phase 1/2 study testing Olaratumab, Gemcitabine and Docetaxel in people with Soft Tissue Sarcoma, run by Eli Lilly and Company at 48 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Soft Tissue Sarcoma
What is being tested?
Olaratumab, Gemcitabine and Docetaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
310 participants
Where
48 sitesin 10 countries
Study dates
1 Mar 2016to 27 Apr 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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 locations and contacts

48 sites in 10 countries.

48 sites in 10 countries

United States21 sites

  • Georgia Cancer Specialists PC

    Atlanta, Georgia, 30342

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

  • Johns Hopkins University School of Medicine

    Baltimore, Maryland, 21287

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • University of Texas Southwestern Medical Center at Dallas

    Dallas, Texas, 75390

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Mayo Clinic-Jacksonville

    Jacksonville, Florida, 32224

  • Monter Cancer Center

    Lake Success, New York, 11042

  • Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232-6307

  • Columbia University Medical Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Nebraska Methodist Cancer Center

    Omaha, Nebraska, 68114

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111-2497

  • Utah Cancer Specialists

    Salt Lake City, Utah, 84106

  • UCLA Medical Center

    Santa Monica, California, 90404

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Washington University Medical School

    St Louis, Missouri, 63110

  • Oklahoma Cancer Specialists & Research Institute, LLC

    Tulsa, Oklahoma, 74146

Other trials in United States

Germany6 sites

  • Helios Klinikum Bad Saarow

    Bad Saarow, Brandenburg, 15526

  • HELIOS Klinikum Berlin-Buch

    Berlin, 13125

  • Medizinische Hochschule Hannover

    Hanover, Lower Saxony, 30625

  • Klinikum der Universität München

    München, Bavaria, 81377

  • Universitätsklinikum Regensburg

    Regensburg, Bavaria, 93053

  • Universitätsklinikum Ulm

    Ulm, Baden-Wurttemberg, 89081

Other trials in Germany

Israel4 sites

  • Rambam Medical Center

    Haifa, 3525408

  • Rabin Medical Center

    Petah Tikva, 4941492

  • Tel Aviv Sourasky Medical Center

    Tel Aviv, 6423906

  • Sheba Medical Center

    Tel HaShomer, Ramat Gan, 5265601

Other trials in Israel

Spain4 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

Other trials in Spain

United Kingdom4 sites

  • Clatterbridge Cancer Centre

    Bebbington, Merseyside, CH63 4JY

  • Western General Hospital

    Edinburgh, Scotland, EH4 2XU

  • University College Hospital - London

    London, Greater London, NW1 2BU

  • Royal Marsden NHS Trust

    London, Greater London, SW3 6JJ

Other trials in United Kingdom

France3 sites

  • Institut Bergonie

    Bordeaux, 33076

  • Centre Oscar Lambret

    Lille, 59020

  • Gustave Roussy

    Villejuif, 94805

Other trials in France

Australia2 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

Other trials in Australia

Italy2 sites

  • Fondazione Piemonte l'Oncologia-Istituto Ricerca Cura Cancro

    Candiolo, Torino, 10060

  • Humanitas Gradenigo

    Torino, 10153

Other trials in Italy

Hungary1 site

  • Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz

    Szolnok, 5000

Other trials in Hungary

Poland1 site

  • Centrum Onkologii-Instytut im Marii Sklodowskiej-Curie

    Warsaw, 02-781

Other trials in Poland

About this study

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

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.

Being tested
Olaratumab, Gemcitabine, Docetaxel, Placebo
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OlaratumabDrug

    Also called LY3012207, IMC-3G3

    Administered IV

  • GemcitabineDrug

    Also called LY188011, Gemzar

    Administered IV

  • DocetaxelDrug

    Administered IV

  • PlaceboDrug

    Administered IV

Study groups in NCT02659020
Study groupRoleWhat they receive
Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + DocetaxelExperimentalParticipants 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.
Receives: Drug: Olaratumab; Drug: Gemcitabine; Drug: Docetaxel
Phase 1b: Cohort 2 overall - 20 mg/kg Olaratumab + Gemcitabine + DocetaxelExperimentalParticipants 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).
Receives: Drug: Olaratumab; Drug: Gemcitabine; Drug: Docetaxel
Phase 2: Olaratumab + Gemcitabine + DocetaxelExperimentalParticipants 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.
Receives: Drug: Olaratumab; Drug: Gemcitabine; Drug: Docetaxel
Phase 2: Placebo + Gemcitabine + DocetaxelPlacebo comparatorParticipants 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.
Receives: Drug: Gemcitabine; Drug: Docetaxel; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Cycle 1 (Up To 21 Days)

  2. 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.

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

Secondary outcomes (17)

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

    Cmax of Olaratumab.

    Measured: 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

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

    Cmin of Olaratumab.

    Measured: 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

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

    T1/2 of Olaratumab.

    Measured: 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

  4. Phase 1b/2: PK: Cmax of Gemcitabine

    Cmax of Gemcitabine.

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

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

    AUC[0-∞] of Gemcitabine

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

  6. Phase 1b/2: PK: Cmax of Docetaxel

    Cmax of Docetaxel.

    Measured: 5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8

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

    AUC [0-∞] of Docetaxel.

    Measured: 5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8

  8. Phase 1b/2: Population PK: Clearance of Olaratumab

    Population PK: Clearance of Olaratumab

    Measured: Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8

  9. Phase 1b/2: Population PK: Volume of Distribution at Steady State (Vss) of Olaratumab

    The Vss is the sum of central volume of distribution (V1) + peripheral volume of distribution (V2).

    Measured: Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8

  10. Phase 2: Overall Survival (Olaratumab Pre-Treated)

    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.

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

  11. Phase 2: Progression Free Survival (PFS)

    PFS was defined as the time from randomization to the first date of radiologic disease progression (as defined by Response Evaluation Criteria In Solid Tumors, Version 1.1 [RECIST v.1.1]) or death due to any cause. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment, if available, or date of randomization if no post-baseline radiographic assessment is available.

    Measured: Baseline to Objective Disease Progression or Death from Any Cause (Up To 38 Months)

  12. Phase 2: Percentage of Participants With a Complete or Partial Response (Objective Response Rate [ORR])

    ORR is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

    Measured: Baseline to Objective Disease Progression or Start of New Anti-Cancer Therapy (Up To 38 Months)

  13. Phase 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD)

    DCR is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

    Measured: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 38 Months)

  14. Phase 2: Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score"

    The mBPI-sf is a 11-item instrument used as a multiple-item measure of cancer pain intensity ranging from 0 (no pain or does not interfere) and ranged through 10 (pain as bad as you can imagine or completely interferes). Time to first worsening of the mBPI-sf "worst pain score" (TWP) was defined as the time from the date of randomization to the first date of either a "worst pain" score increase of greater than or equal to (≥) 2 points from baseline or an analgesic drug class increase of ≥1 level. If the patient has not worsened by either of these criteria, TWP was censored for analysis on the last date the mBPI-sf was administered.

    Measured: Baseline to Follow-up (Up To 24 Months)

  15. Phase 2: Time to First Worsening of Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Symptom Scales.

    The EORTC QLQ-C30 is a self-reported general cancer instrument consisting of 30 items covered by 1 of 3 dimensions: global health status/quality of life (2 items), functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea, or financial impact). Time to first worsening of Symptom Burden was defined as the time from randomization to the first observation of worsening on symptom scales (i.e.,) increase of at least 10 points from baseline. For symptom scales, a linear transformation was used to obtain total score ranging from 0 to 100, a high score represents a high level of symptomatology or problems.

    Measured: Baseline to Follow-up (Up to 33 months)

  16. Phase 2: Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L)

    The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) of health status are each assessed with 5 response options (1=no problem, 2=slight, 3=moderate, 4=severe, and 5=extreme problem) and scored as a composite index which were anchored on a scale of 0 to 1 with a higher score representing better health status. Additionally, current health status was assessed on a visual analogue scale (VAS) ranging from 0 to 100 with a higher score representing better health status.

    Measured: Cycle 1 (Day 1), Follow-up (Up to 38 Months)

  17. Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies

    Number of Participants with Treatment Emergent Anti-Olaratumab Antibodies

    Measured: Baseline through Follow-Up (Up to 38 Months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jan 2016 (estimated)
  2. Study start1 Mar 2016
  3. Primary completion28 Jul 2020
  4. Study completion27 Apr 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
310 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02659020
Sponsor's protocol ID
15839
Other IDs
I5B-MC-JGDL, 2015-001316-34, 2015
Acronym
ANNOUNCE 2
Status last verified
Apr 2022
First submitted
15 Jan 2016
Last updated
9 May 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
Individual data sharing
Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Olaratumab, Gemcitabine and Docetaxel in people with Soft Tissue Sarcoma, run by Eli Lilly and Company at 48 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in United States, Germany, Israel, Spain, United Kingdom and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT) (time frame: Cycle 1 (Up To 21 Days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02659020.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2022.

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