Advanced or Metastatic Soft Tissue Sarcoma / Soft Tissue Sarcoma
Conditions
Interventions
Eligible patients will be randomized 1:1 into 1 of 2 treatment options
(olaratumab plus
doxorubicin or placebo plus doxorubicin).
Patients assigned to the investigational arm will receive 2 loading
Sponsors
Eli Lilly
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Patients are eligible to be included in the study only if they meet all of the following criteria: [1] The patient signed an ICF and authorization for release of health information for research prior to any study-specific procedures being performed. [2] The patient is aged >= 18 years at study entry. [3] The patient has histologically confirmed diagnosis of locally advanced unresectable or metastatic STS not amenable to curative treatment with surgery or radiotherapy. Patients with a diagnosis of Grade 1 liposarcoma are eligible if there is histological or radiographic evidence of evolution to more aggressive disease. Patients with Kaposi*s sarcoma and gastrointestinal stromal tumors (GIST) will be excluded. Note: Evidence of disease progression is required for patients that are not newly diagnosed. [4] The patient has measurable or nonmeasurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1, Eisenhauer et al. 2009; refer to Attachment 6 of the Protocol). Tumors within a previously irradiated field will be designated as *nontarget* lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiotherapy. [5] The patient has a performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale (refer to Attachment 4 of the Protocol). [6] The patient has not received any previous treatment with anthracyclines. [7] The patient may have had any number of prior systemic cytotoxic therapies for advanced/metastatic disease and are considered appropriate candidates for anthracycline therapy. All previous anticancer treatments must be completed >= 3 weeks (21 days) prior to first dose of study drug. [8] The patient has resolution of adverse events and of all clinically significant toxic effects of prior locoregional therapy, surgery, radiotherapy, or systemic anticancer therapy to =1.5 x 109/L. Granulocyte colony-stimulating factor (G-CSF) cannot be administered within 2 weeks (14 days) prior to randomization. • Platelet count >=100 x 109/L • Hemoglobin >=9.0 g/dL. No transfusions are allowed within 2 weeks (14 days) prior to randomization. • The creatinine clearance is >=45 mL/min (refer to Attachment 5 for the Cockcroft-Gault formula) Proteinuria =2+ proteinuria) • Total bilirubin below upper limit of normal (ULN) (except for patients with Gilbert*s Syndrome, who must have a total bilirubin <3 mg/dL) • Alanine aminotransferase/aspartate aminotransferase (AST/ALT) <= 3.0 × ULN; if the liver has tumor inv
Exclusion criteria
Exclusion criteria: Patients will be excluded from the study if they meet any of the following criteria: [15] The patient is diagnosed with GIST or Kaposi sarcoma. [16] The patient has active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of randomization. Patients 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. Patients with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before randomization to rule out brain metastasis. [17] The patient has received prior treatment with doxorubicin, epirubicin, idarubicin, and/or other anthracyclines or anthracenediones; the patient has received prior treatment with olaratumab or has participated in a prior olaratumab trial. [18] The patient had prior radiotherapy of the mediastinal/pericardial area or whole pelvis radiation. [19] The patient has history of another primary cancer, with the exception of a) curatively treated non-melanomatous skin cancer, b) curatively treated cervical carcinoma in situ, c) other primary non-hematologic malignancies or solid tumor treated with curative intent, no known active disease and no treatment administered during the last 3 years prior to randomization. [20] The patient has electively planned or will require major surgery during the course of the study. [21] The patient has uncontrolled intercurrent illness including, but not limited to, an ongoing/active infection requiring parenteral antibiotics, symptomatic congestive heart failure (CHF), left ventricular dysfunction (LVEF 450 msec for males and >470 msec for females on screening electrocardiogram (ECG) utilizing Bazett*s correction (refer to formula in Table JGDJ.8 of the Protocol). [25] Females who are pregnant or breastfeeding [26] The patient has a known allergy to any of the treatment components including a history of allergic reactions attributed to compounds of chemical or biological composition similar to olaratumab. [27] The patient is enrolled in, or discontinued study treatment from another trial involving an investigational agent or use of non-approved drug or device within 28 days of being randomized in this trial, or concurrent enrollment in any other type of medical research judged scientifically or medically incompatible with this trial. Patients participating in surveys or observational studies are eligible to participate in this study. [28] DELETED. [29] The patient has a known investigator-assessed active fungal, bacterial, or viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy: Overall survival (time from randomization to death) is the primary per-patient measure for efficacy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy: Radiographic assessments will be performed according to Response Evaluation Criteria in Solid Tumors (Response Evaluation Criteria in Solid Tumors [RECIST], Version 1.1) criteria, will be performed every 6 weeks (±7 days) until radiographic documentation of PD. The following additional efficacy measures will be determined for each patient, with planned statistical analyses specified in Section 12 of the Protocol. * Progression-free survival (PFS) Objective Response Rate (ORR) Disease Control Rate (DCR) Time to first worsening of the mBPI-sf (Brief Pain Inventory Short Form Modified) *worst pain* score Duration of disease control (DDC) Time to any progression (censoring for death without progression) Time to any new metastases (censoring for death and for other type of PD) New-metastases-free survival (nMFS) Time to any progression based solely on increased sum of target lesions Time to first worsening of the QLQ-C30 scale scores (for example, Global Health Status / Quality of Life score, Physical Functioning score, and Role Functioning score) Time to first worsening of ECOG performance status Second PFS (PFS2) after end of study treatment while on subsequent anticancer therapy Safety: Safety will be evaluated based on reported adverse events (AEs), physical examinations, vital signs, laboratory tests, electrocardiograms (ECGs), and results from echocardiograms (ECHOs) or multigated acquisition (MUGA) scans. Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRATM) and graded using the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0. Clinical laboratory toxicity will be graded using NCI-CTCAE criteria, Version 4.0. Patient-Reported Outcomes (PROs): Pain will be assessed with the Brief Pain Inventory Short Form Modified [mBPI-sf], HRQoL will be assessed with The European Organization for Research and Treatment of Cancer Quality of Life Q | — |
Countries
Netherlands
Outcome results
None listed