Back to resultsA Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma (ANNOUNCE 2)
Primary Purpose
Soft Tissue Sarcoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Olaratumab
Gemcitabine
Docetaxel
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Soft Tissue Sarcoma
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).
Sites / Locations
- UCLA Medical Center
- University of Colorado Cancer Center
- Mayo Clinic-Jacksonville
- Sylvester Comprehensive Cancer Center
- Georgia Cancer Specialists PC
- Johns Hopkins University School of Medicine
- Dana Farber Cancer Institute
- Washington University Medical School
- Nebraska Methodist Cancer Center
- Monter Cancer Center
- Columbia University Medical Center
- Memorial Sloan Kettering Cancer Center
- Ohio State University Medical Center
- Oklahoma Cancer Specialists & Research Institute, LLC
- Fox Chase Cancer Center
- Vanderbilt University Medical Center
- University of Texas Southwestern Medical Center at Dallas
- University of Texas MD Anderson Cancer Center
- Utah Cancer Specialists
- Seattle Cancer Care Alliance
- Medical College of Wisconsin
- Royal Adelaide Hospital
- Peter MacCallum Cancer Centre
- Institut Bergonie
- Centre Oscar Lambret
- Gustave Roussy
- Universitätsklinikum Ulm
- Klinikum der Universität München
- Universitätsklinikum Regensburg
- Helios Klinikum Bad Saarow
- Medizinische Hochschule Hannover
- HELIOS Klinikum Berlin-Buch
- Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz
- Sheba Medical Center
- Rambam Medical Center
- Rabin Medical Center
- Tel Aviv Sourasky Medical Center
- Fondazione Piemonte l'Oncologia-Istituto Ricerca Cura Cancro
- Humanitas Gradenigo
- Centrum Onkologii-Instytut im Marii Sklodowskiej-Curie
- Hospital Universitari Vall d'Hebron
- Hospital Universitario 12 de Octubre
- Hospital Universitario La Paz
- Hospital Universitario Virgen del Rocio
- University College Hospital - London
- Royal Marsden NHS Trust
- Clatterbridge Cancer Centre
- Western General Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
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
Arm Description
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.
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).
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.
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.
Outcomes
Primary Outcome Measures
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:
Febrile neutropenia with documented Grade ≥3 infection or sepsis
Grade 4 neutropenia lasting 7 days or longer.
Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by hemorrhage.
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.
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.
Secondary Outcome Measures
Phase 1b: Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab
Cmax of Olaratumab.
Phase 1b: PK: Minimum Serum Concentration (Cmin) of Olaratumab
Cmin of Olaratumab.
Phase 1b: PK: Elimination Half-Life (T1/2) of Olaratumab
T1/2 of Olaratumab.
Phase 1b/2: PK: Cmax of Gemcitabine
Cmax of Gemcitabine.
Phase 1b/2: PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of Gemcitabine
AUC[0-∞] of Gemcitabine
Phase 1b/2: PK: Cmax of Docetaxel
Cmax of Docetaxel.
Phase 1b/2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-∞]) of Docetaxel
AUC [0-∞] of Docetaxel.
Phase 1b/2: Population PK: Clearance of Olaratumab
Population PK: Clearance of Olaratumab
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).
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.
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.
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.
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.
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.
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.
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.
Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies
Number of Participants with Treatment Emergent Anti-Olaratumab Antibodies
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02659020
Brief Title
A Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma
Acronym
ANNOUNCE 2
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
March 1, 2016 (Actual)
Primary Completion Date
July 28, 2020 (Actual)
Study Completion Date
April 27, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Soft Tissue Sarcoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
310 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1b: Cohort 2 overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel
Arm Type
Experimental
Arm Description
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).
Arm Title
Phase 2: Olaratumab + Gemcitabine + Docetaxel
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2: Placebo + Gemcitabine + Docetaxel
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Olaratumab
Other Intervention Name(s)
LY3012207, IMC-3G3
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
LY188011, Gemzar
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered IV
Primary Outcome Measure Information:
Title
Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT)
Description
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:
Febrile neutropenia with documented Grade ≥3 infection or sepsis
Grade 4 neutropenia lasting 7 days or longer.
Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by hemorrhage.
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.
Time Frame
Cycle 1 (Up To 21 Days)
Title
Phase 2: Overall Survival (OS) (Olaratumab-Naive)
Description
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.
Time Frame
Baseline to Date of Death Due to Any Cause (Up To 38 Months)
Secondary Outcome Measure Information:
Title
Phase 1b: Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab
Description
Cmax of Olaratumab.
Time Frame
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
Title
Phase 1b: PK: Minimum Serum Concentration (Cmin) of Olaratumab
Description
Cmin of Olaratumab.
Time Frame
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
Title
Phase 1b: PK: Elimination Half-Life (T1/2) of Olaratumab
Description
T1/2 of Olaratumab.
Time Frame
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
Title
Phase 1b/2: PK: Cmax of Gemcitabine
Description
Cmax of Gemcitabine.
Time Frame
Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)
Title
Phase 1b/2: PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of Gemcitabine
Description
AUC[0-∞] of Gemcitabine
Time Frame
Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)
Title
Phase 1b/2: PK: Cmax of Docetaxel
Description
Cmax of Docetaxel.
Time Frame
5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8
Title
Phase 1b/2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-∞]) of Docetaxel
Description
AUC [0-∞] of Docetaxel.
Time Frame
5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8
Title
Phase 1b/2: Population PK: Clearance of Olaratumab
Description
Population PK: Clearance of Olaratumab
Time Frame
Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8
Title
Phase 1b/2: Population PK: Volume of Distribution at Steady State (Vss) of Olaratumab
Description
The Vss is the sum of central volume of distribution (V1) + peripheral volume of distribution (V2).
Time Frame
Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8
Title
Phase 2: Overall Survival (Olaratumab Pre-Treated)
Description
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.
Time Frame
Baseline to Date of Death Due to Any Cause (Up To 38 Months)
Title
Phase 2: Progression Free Survival (PFS)
Description
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.
Time Frame
Baseline to Objective Disease Progression or Death from Any Cause (Up To 38 Months)
Title
Phase 2: Percentage of Participants With a Complete or Partial Response (Objective Response Rate [ORR])
Description
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.
Time Frame
Baseline to Objective Disease Progression or Start of New Anti-Cancer Therapy (Up To 38 Months)
Title
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)
Description
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.
Time Frame
Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 38 Months)
Title
Phase 2: Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score"
Description
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.
Time Frame
Baseline to Follow-up (Up To 24 Months)
Title
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.
Description
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.
Time Frame
Baseline to Follow-up (Up to 33 months)
Title
Phase 2: Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L)
Description
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.
Time Frame
Cycle 1 (Day 1), Follow-up (Up to 38 Months)
Title
Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies
Description
Number of Participants with Treatment Emergent Anti-Olaratumab Antibodies
Time Frame
Baseline through Follow-Up (Up to 38 Months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
UCLA Medical Center
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
University of Colorado Cancer Center
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Mayo Clinic-Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Georgia Cancer Specialists PC
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Johns Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Washington University Medical School
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Nebraska Methodist Cancer Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
Monter Cancer Center
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Oklahoma Cancer Specialists & Research Institute, LLC
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74146
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111-2497
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-6307
Country
United States
Facility Name
University of Texas Southwestern Medical Center at Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Utah Cancer Specialists
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Facility Name
Institut Bergonie
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Centre Oscar Lambret
City
Lille Cedex
ZIP/Postal Code
59020
Country
France
Facility Name
Gustave Roussy
City
Villejuif Cedex
ZIP/Postal Code
94805
Country
France
Facility Name
Universitätsklinikum Ulm
City
Ulm
State/Province
Baden-Württemberg
ZIP/Postal Code
89081
Country
Germany
Facility Name
Klinikum der Universität München
City
München
State/Province
Bayern
ZIP/Postal Code
81377
Country
Germany
Facility Name
Universitätsklinikum Regensburg
City
Regensburg
State/Province
Bayern
ZIP/Postal Code
93053
Country
Germany
Facility Name
Helios Klinikum Bad Saarow
City
Bad Saarow
State/Province
Brandenburg
ZIP/Postal Code
15526
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30625
Country
Germany
Facility Name
HELIOS Klinikum Berlin-Buch
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz
City
Szolnok
ZIP/Postal Code
5000
Country
Hungary
Facility Name
Sheba Medical Center
City
Tel Hashomer
State/Province
Ramat Gan
ZIP/Postal Code
5265601
Country
Israel
Facility Name
Rambam Medical Center
City
Haifa
ZIP/Postal Code
3525408
Country
Israel
Facility Name
Rabin Medical Center
City
Petah Tiqva
ZIP/Postal Code
4941492
Country
Israel
Facility Name
Tel Aviv Sourasky Medical Center
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
Facility Name
Fondazione Piemonte l'Oncologia-Istituto Ricerca Cura Cancro
City
Candiolo
State/Province
Torino
ZIP/Postal Code
10060
Country
Italy
Facility Name
Humanitas Gradenigo
City
Torino
ZIP/Postal Code
10153
Country
Italy
Facility Name
Centrum Onkologii-Instytut im Marii Sklodowskiej-Curie
City
Warszawa
ZIP/Postal Code
02-781
Country
Poland
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
University College Hospital - London
City
London
State/Province
Greater London
ZIP/Postal Code
NW1 2BU
Country
United Kingdom
Facility Name
Royal Marsden NHS Trust
City
London
State/Province
Greater London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
Clatterbridge Cancer Centre
City
Bebbington
State/Province
Merseyside
ZIP/Postal Code
CH63 4JY
Country
United Kingdom
Facility Name
Western General Hospital
City
Edinburgh
State/Province
Scotland
ZIP/Postal Code
EH4 2XU
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing 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.
IPD Sharing Access Criteria
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
IPD Sharing URL
https://vivli.org/
Links:
URL
https://trials.lillytrialguide.com/en-US/trial/3Jz0lQ8yUE2Q42EWCOQKWq
Description
A Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma (ANNOUNCE-2)
Learn more about this trial
A Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma
We'll reach out to this number within 24 hrs