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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02659020




Registration number
NCT02659020
Ethics application status
Date submitted
15/01/2016
Date registered
20/01/2016
Date last updated
9/05/2022

Titles & IDs
Public title
A Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma
Scientific 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
Secondary ID [1] 0 0
I5B-MC-JGDL
Secondary ID [2] 0 0
15839
Universal Trial Number (UTN)
Trial acronym
ANNOUNCE 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Soft Tissue Sarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Olaratumab
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Docetaxel
Treatment: Drugs - Placebo

Experimental: 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.

Experimental: 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).

Experimental: 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.

Placebo Comparator: 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.


Treatment: Drugs: Olaratumab
Administered IV

Treatment: Drugs: Gemcitabine
Administered IV

Treatment: Drugs: Docetaxel
Administered IV

Treatment: Drugs: Placebo
Administered IV

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT)
Timepoint [1] 0 0
Cycle 1 (Up To 21 Days)
Primary outcome [2] 0 0
Phase 2: Overall Survival (OS) (Olaratumab-Naive)
Timepoint [2] 0 0
Baseline to Date of Death Due to Any Cause (Up To 38 Months)
Secondary outcome [1] 0 0
Phase 1b: Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
Phase 1b: PK: Minimum Serum Concentration (Cmin) of Olaratumab
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
Phase 1b: PK: Elimination Half-Life (T1/2) of Olaratumab
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Phase 1b/2: PK: Cmax of Gemcitabine
Timepoint [4] 0 0
Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)
Secondary outcome [5] 0 0
Phase 1b/2: PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-8]) of Gemcitabine
Timepoint [5] 0 0
Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)
Secondary outcome [6] 0 0
Phase 1b/2: PK: Cmax of Docetaxel
Timepoint [6] 0 0
5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8
Secondary outcome [7] 0 0
Phase 1b/2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-8]) of Docetaxel
Timepoint [7] 0 0
5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8
Secondary outcome [8] 0 0
Phase 1b/2: Population PK: Clearance of Olaratumab
Timepoint [8] 0 0
Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8
Secondary outcome [9] 0 0
Phase 1b/2: Population PK: Volume of Distribution at Steady State (Vss) of Olaratumab
Timepoint [9] 0 0
Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8
Secondary outcome [10] 0 0
Phase 2: Overall Survival (Olaratumab Pre-Treated)
Timepoint [10] 0 0
Baseline to Date of Death Due to Any Cause (Up To 38 Months)
Secondary outcome [11] 0 0
Phase 2: Progression Free Survival (PFS)
Timepoint [11] 0 0
Baseline to Objective Disease Progression or Death from Any Cause (Up To 38 Months)
Secondary outcome [12] 0 0
Phase 2: Percentage of Participants With a Complete or Partial Response (Objective Response Rate [ORR])
Timepoint [12] 0 0
Baseline to Objective Disease Progression or Start of New Anti-Cancer Therapy (Up To 38 Months)
Secondary outcome [13] 0 0
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)
Timepoint [13] 0 0
Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 38 Months)
Secondary outcome [14] 0 0
Phase 2: Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score"
Timepoint [14] 0 0
Baseline to Follow-up (Up To 24 Months)
Secondary outcome [15] 0 0
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.
Timepoint [15] 0 0
Baseline to Follow-up (Up to 33 months)
Secondary outcome [16] 0 0
Phase 2: Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L)
Timepoint [16] 0 0
Cycle 1 (Day 1), Follow-up (Up to 38 Months)
Secondary outcome [17] 0 0
Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies
Timepoint [17] 0 0
Baseline through Follow-Up (Up to 38 Months)

Eligibility
Key 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).
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Nebraska
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Oklahoma
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
United States of America
State/province [17] 0 0
Wisconsin
Country [18] 0 0
France
State/province [18] 0 0
Bordeaux
Country [19] 0 0
France
State/province [19] 0 0
Lille Cedex
Country [20] 0 0
France
State/province [20] 0 0
Villejuif Cedex
Country [21] 0 0
Germany
State/province [21] 0 0
Baden-Württemberg
Country [22] 0 0
Germany
State/province [22] 0 0
Bayern
Country [23] 0 0
Germany
State/province [23] 0 0
Brandenburg
Country [24] 0 0
Germany
State/province [24] 0 0
Niedersachsen
Country [25] 0 0
Germany
State/province [25] 0 0
Berlin
Country [26] 0 0
Hungary
State/province [26] 0 0
Szolnok
Country [27] 0 0
Israel
State/province [27] 0 0
Ramat Gan
Country [28] 0 0
Israel
State/province [28] 0 0
Haifa
Country [29] 0 0
Israel
State/province [29] 0 0
Petah Tiqva
Country [30] 0 0
Israel
State/province [30] 0 0
Tel Aviv
Country [31] 0 0
Italy
State/province [31] 0 0
Torino
Country [32] 0 0
Poland
State/province [32] 0 0
Warszawa
Country [33] 0 0
Spain
State/province [33] 0 0
Barcelona
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid
Country [35] 0 0
Spain
State/province [35] 0 0
Sevilla
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Greater London
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Merseyside
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Scotland

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02659020
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02659020