A Phase 1 interventional study of Olaratumab and Doxorubicin in Soft Tissue Sarcoma, sponsored by Eli Lilly and Company. Completed at 14 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-08-12.
Sponsored by Eli Lilly and Company · Phase 1, Interventional, and Treatment
The purpose of this study is to evaluate potential biomarkers and method of action, efficacy and safety of olaratumab in participants with soft tissue sarcoma (STS).
1,667 studies on the registry are indexed under Sarcoma; 393 are open to participants now.
This study's enrollment of 51 is above the median of 40 across 1,283 interventional studies indexed under Sarcoma.
Browse Sarcoma studies →Eli Lilly and Company is the lead sponsor of 2,048 studies on the registry; 140 are open to participants now.
Of its 521 completed or terminated interventional studies of FDA-regulated products, 341 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Cycle 1: Olaratumab 20 milligram per kilogram (mg/kg) given intravenously (IV) on Day 1 and Day 8 (21 day cycle). Cycle 2: Olaratumab 20 mg/kg given IV on Day 1 and Day 8 plus doxorubicin 75 mg/m2 given IV on Day 1 (21 day cycle). Cycle 3 through Cycle 7: Olaratumab 15 mg/kg given IV on Day 1 and Day 8 plus doxorubicin 75 mg/m2 given IV on Day 1 (21 day cycles).
Drug: Olaratumab · Drug: Doxorubicin
Olaratumab given IV on Day 1 and Day 8 (21 day cycle) concurrently with radiotherapy. Radiotherapy addendum was not implemented.
Drug: Olaratumab · Radiation: External Beam Radiotherapy
Administered IV
Also known as: LY3012207
Administered IV
Percent Change From Baseline in Enumeration of Circulating Tumor Cells (CTCs) in Whole Blood
Enumeration of CTCs pre- and post- treatment with olaratumab may be a useful biomarker given the predilection for sarcomas to spread hematogenously.
Time frame: Baseline, End of Cycle 1 (21 days)
Percent Change From Baseline in Gene Expression of Platelet-Derived Growth Factor Receptor Alpha (PGDFRα) and PGDFR Beta (β) in Tumor Tissue
Over-activity of PDGF signaling is associated with the development of certain malignant diseases. Olaratumab is an IgG1 antagonist of PDGFRα.
Time frame: Baseline, End of Cycle 1 (21 days)
Percent Change From Baseline in Gene Expression of PDGF A, PDGF B, PDGF C, and PDGF-D Canonical Ligands in Tumor Tissue
PDGF A, PDGF B, PDGF C, and PDGF D are platelet-derived growth factor canonical ligands associated with activation of PDGFR α and β.
Time frame: Baseline, End of Cycle 1 (21 days)
Progression Free Survival (PFS)
Progression-free survival (PFS) is defined as the time from the date of first study dose to the first date of radiologic disease progression or death due to any cause. Progressive disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression.
Time frame: Baseline to Objective Progression or Death from Any Cause (Up to 18 Months)
Objective Response Rate (ORR): Percent of Participants With Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR)
Overall Response Rate (ORR) is defined as the percentage of participants achieving a best overall response of either Complete Response (CR) or Partial Response (PR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR is defined as a disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10 mm and normalization of tumor marker results; PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. The best overall response is the best response from the start of the treatment until progressive disease (PD)/recurrence.
Time frame: Baseline to Measured Progressive Disease (Up to 18 Months)
Disease Control Rate (DCR): Percent of Participants Who Exhibit Stable Disease (SD), CR or PR
Disease control rate (DCR) is defined as the percentage of participants achieving a best overall response of CR, PR, or SD as determined by RECIST 1.1. CR is defined as a disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10 mm and normalization of tumor marker results; PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters; SD is defined as neither sufficient shrinking to qualify as PR nor sufficient increase to qualify for PD. Participants who do not have any post-baseline tumor response assessments for any reason are considered non-responders and are included in the denominator when calculating the response rate.
Time frame: Baseline to Measured Progressive Disease (Up to 18 Months)
Percentage of Participants With Resectable Tumors (Resectability Rate)
Resectability rate is obtained when the total number of participants with resectable tumors is divided by the total number of participants. Resectability of a tumor is determined by the surgeon and multi-disciplinary team and dependent on tumor stage and the participants coexisting medical conditions.
Time frame: Cycle 1 through Cycle 7 (Up to 6 Months)
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Monotherapy
Summary of Cmax of olaratumab monotherapy on Cycle 1 Day 1 and Day 8
Time frame: Cycle 1 Days 1 and 8: Predose; 5 minutes(m) post-infusion
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab
Cmax of olaratumab Cycles 2 and 3 Day 1 and 8 of a 21-day cycle.
Time frame: Cycle 2 Day 1: Predose, 5 minutes(m) post-infusion, 24 hours(h), 96h; Day 8:Predose, 5 m, and 24h, 48h, 96h, and 240h postdose; Cycle 3 Day 1 and Day 8: Predose and 5m post-infusion
Number of Participants With Anti-Olaratumab Antibodies
A participant is counted as positive if they had at least one anti-olaratumab antibody positive result during the study.
Time frame: Predose Cycle 1 Day 1 through Follow-Up (Up to 8 Months)
Participants are considered to have completed the study if they completed one cycle of monotherapy and all 6 cycles of combination therapy.
| Milestone | Olaratumab + Doxorubicin |
|---|---|
| Started | 51 |
| Received at least one dose of study drug | 51 |
| Completed | 11 |
| Not completed | 40 |
| Withdrew: Progressive disease | 23 |
| Withdrew: Surgical resection | 10 |
| Withdrew: Adverse event | 4 |
| Withdrew: Physician decision | 2 |
| Withdrew: Death | 1 |
Enumeration of CTCs pre- and post- treatment with olaratumab may be a useful biomarker given the predilection for sarcomas to spread hematogenously.
| percent change | Olaratumab |
|---|---|
| Traditional CTCs | 846.93 ± 3260.60 |
| All Population CTCs | 820.11 ± 3263.41 |
Over-activity of PDGF signaling is associated with the development of certain malignant diseases. Olaratumab is an IgG1 antagonist of PDGFRα.
| percent change in gene expression | Olaratumab |
|---|---|
| PDGF Receptor α | 6162.86 ± 32383.49 |
| PDGF Receptor β | 1246.25 ± 7024.82 |
PDGF A, PDGF B, PDGF C, and PDGF D are platelet-derived growth factor canonical ligands associated with activation of PDGFR α and β.
| percent change in gene expression | Olaratumab |
|---|---|
| Canonical Ligand PDGF - A | 189.37 ± 672.91 |
| Canonical Ligand PDGF - B | 602.01 ± 2798.92 |
| Canonical Ligand PDGF - C | 1107.45 ± 6053.12 |
| Canonical Ligand PDGF - D | 2630.36 ± 14425.92 |
Progression-free survival (PFS) is defined as the time from the date of first study dose to the first date of radiologic disease progression or death due to any cause. Progressive disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression.
| months | Olaratumab + Doxorubicin |
|---|---|
| Progression Free Survival (PFS) | 2.86 (1.41 to 9.72) |
Overall Response Rate (ORR) is defined as the percentage of participants achieving a best overall response of either Complete Response (CR) or Partial Response (PR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR is defined as a disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10 mm and normalization of tumor marker results; PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. The best overall response is the best response from the start of the treatment until progressive disease (PD)/recurrence.
| percentage of participants | Olaratumab + Doxorubicin |
|---|---|
| Objective Response Rate (ORR): Percent of Participants With Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) | 11.8 |
Disease control rate (DCR) is defined as the percentage of participants achieving a best overall response of CR, PR, or SD as determined by RECIST 1.1. CR is defined as a disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10 mm and normalization of tumor marker results; PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters; SD is defined as neither sufficient shrinking to qualify as PR nor sufficient increase to qualify for PD. Participants who do not have any post-baseline tumor response assessments for any reason are considered non-responders and are included in the denominator when calculating the response rate.
| percentage of participants | Olaratumab + Doxorubicin |
|---|---|
| Disease Control Rate (DCR): Percent of Participants Who Exhibit Stable Disease (SD), CR or PR | 52.9 |
Resectability rate is obtained when the total number of participants with resectable tumors is divided by the total number of participants. Resectability of a tumor is determined by the surgeon and multi-disciplinary team and dependent on tumor stage and the participants coexisting medical conditions.
| percentage of participants | Olaratumab + Doxorubicin |
|---|---|
| Percentage of Participants With Resectable Tumors (Resectability Rate) | 35.3 (22.4306 to 49.9318) |
Summary of Cmax of olaratumab monotherapy on Cycle 1 Day 1 and Day 8
| micrograms per milliliter (µg/mL) | Olaratumab |
|---|---|
| Cycle 1 Day 1 | 510 ± 22 |
| Cycle 1 Day 8 | 661 ± 24 |
Cmax of olaratumab Cycles 2 and 3 Day 1 and 8 of a 21-day cycle.
| micrograms per milliliter (µg/mL) | Olaratumab + Doxorubicin |
|---|---|
| Cycle 2 Day 1 | 624 ± 26 |
| Cycle 2 Day 8 | 711 ± 28 |
| Cycle 3 Day 1 | 521 ± 30 |
| Cycle 3 Day 8 | 601 ± 32 |
A participant is counted as positive if they had at least one anti-olaratumab antibody positive result during the study.
| Participants | Olaratumab + Doxorubicin |
|---|---|
| Number of Participants With Anti-Olaratumab Antibodies | 1 |
Collected over Baseline to end of study (Up to 46 months). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Olaratumab + Doxorubicin | 3/51 (5.9%) | 22/51 (43.1%) | 50/51 (98%) |
| Event | Olaratumab + Doxorubicin |
|---|---|
| Febrile neutropeniaBlood and lymphatic system disorders | 9/51 |
| SepsisInfections and infestations | 2/51 |
| AnaemiaBlood and lymphatic system disorders | 1/51 |
| Atrial fibrillationCardiac disorders | 1/51 |
| Cardiopulmonary failureCardiac disorders | 1/51 |
| DiarrhoeaGastrointestinal disorders | 1/51 |
| Gastrointestinal obstructionGastrointestinal disorders | 1/51 |
| Intestinal perforationGastrointestinal disorders | 1/51 |
| StomatitisGastrointestinal disorders | 1/51 |
| PyrexiaGeneral disorders | 1/51 |
| Event | Olaratumab + Doxorubicin |
|---|---|
| NauseaGastrointestinal disorders | 27/51 |
| FatigueGeneral disorders | 24/51 |
| StomatitisGastrointestinal disorders | 22/51 |
| ConstipationGastrointestinal disorders | 20/51 |
| Decreased appetiteMetabolism and nutrition disorders | 17/51 |
| AlopeciaSkin and subcutaneous tissue disorders | 16/51 |
| AstheniaGeneral disorders | 13/51 |
| DiarrhoeaGastrointestinal disorders | 12/51 |
| VomitingGastrointestinal disorders | 12/51 |
| AnaemiaBlood and lymphatic system disorders | 11/51 |
All participants who received at least one dose of study drug.
| Age, Categorical(Participants) | Olaratumab + Doxorubicin |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 37 |
| >=65 years | 14 |
| Sex: Female, Male(Participants) | Olaratumab + Doxorubicin |
|---|---|
| Female | 24 |
| Male | 27 |
| Ethnicity (NIH/OMB)(Participants) | Olaratumab + Doxorubicin |
|---|---|
| Hispanic or Latino | 4 |
| Not Hispanic or Latino | 44 |
| Unknown or Not Reported | 3 |
| Race (NIH/OMB)(Participants) | Olaratumab + Doxorubicin |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 2 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 2 |
| White | 47 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(Participants) | Olaratumab + Doxorubicin |
|---|---|
| United States | 17 |
| Italy | 3 |
| United Kingdom | 4 |
| France | 2 |
| Spain | 25 |
| Circulating Tumor Cells (CTC)(CTC per milliliter) | Olaratumab + Doxorubicin |
|---|---|
| Traditional CTC | 2.183 ± 2.631 |
| All Population CTC | 2.446 ± 2.797 |
| Platelet-Derived Growth Factor Receptor Alpha (PGDFRα ) and PGDFR Beta (β)(relative gene expression units) | Olaratumab + Doxorubicin |
|---|---|
| PGDFRα | 301.68 ± 570.79 |
| PGDFRβ | 812.49 ± 1260.23 |
| PDGF Canonical Ligands -A, -B, -C, -D(relative gene expression units) | Olaratumab + Doxorubicin |
|---|---|
| PGDF-A | 12.90 ± 18.46 |
| PDGF-B | 230.62 ± 1151.87 |
| PDGF-C | 227.68 ± 447.56 |
| PDGF-D | 33.22 ± 69.99 |
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