E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or Metastatic Soft Tissue Sarcoma |
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E.1.1.1 | Medical condition in easily understood language |
cancer of the connective tissue that has worsened or grown in other parts of the body |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10041298 |
E.1.2 | Term | Soft tissue sarcomas histology unspecified |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to compare doxorubicin plus olaratumab versus doxorubicin plus placebo with respect to OS in 2 populations:
(1) Patients with advanced or metastatic soft tissue sarcoma (STS) not amenable to treatment with surgery or radiotherapy with curative intent
(2) Patients with advanced or metastatic leiomyosarcoma (LMS) not amenable to treatment with surgery or radiotherapy with curative intent
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to compare doxorubicin plus olaratumab versus doxorubicin plus placebo with respect to:
• Progression-free survival (PFS)
• Objective response rate (ORR) (complete response [CR] + partial response [PR])
• Disease control rate (DCR; CR + PR + stable disease [SD])
• Patient-reported outcomes (PROs): Pain, Health-related Quality of Life (HRQoL), and health status
• Duration of response (DoR)
• Duration of disease control (DDC)
• Safety and tolerability
• Pharmacokinetics (PK) and immunogenicity
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
18 years or older at study entry
Histologically confirmed diagnosis of locally advanced unresectable or metastatic STS not amenable to curative treatment with surgery or radiotherapy. Grade 1 liposarcoma are eligible if there is histological or radiographic evidence of evolution to more aggressive disease. (excludes GIST & Kaposi). Note: Evidence of disease progression is required for patients that are not newly diagnosed.
Measurable or nonmeasurable but evaluable disease by RECIST 1.1
ECOG 0-1
May have had any number of prior systemic therapies for advanced/metastatic disease, however may not have received any previous treatment with anthracyclines. All previous anticancer treatments must be completed ≥ 3 weeks (21 days) prior to first dose of study drug.
Consent to provide archived FFPE tumor tissue or be subject to a pre-treatment re-biopsy of primary or metastatic tumor tissue future central pathology review and translational research (if archived tissue is unavailable)
LVEF ›= 50%
Life expectancy, in opinion of the investigator, is at least 3 months
Females of child-bearing potential must have a negative serum pregnancy test within 7 days prior to randomization.
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E.4 | Principal exclusion criteria |
Diagnosed with GIST or Kaposi sarcoma
Active CNS or brain metastasis at randomization
The patient has received prior treatment with doxorubicin, epirubicin, idarubicin, and/or other anthracyclines or anthracenediones; the patient has received treatment with olaratumab or has participated in a prior olaratumab trial.
Prior radiotherapy of the mediastinal/pericardial area or whole pelvis radiation
Electively planned or required major surgery during the study
Uncontrolled intercurrent illness including, but not limited to, an ongoing/active infection requiring parenteral antibiotics, symptomatic congestive heart failure (CHF), left ventricular dysfunction (LVEF<50%), severe myocardial insufficiency, cardiac arrhythmia, cardiomyopathy, or a psychiatric illness/social situation that would limit compliance with study requirements
Unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction
QTc interval › 450 msec and › 470 msec for males and females, respectively, on screening ECG
Pregnant or breastfeeding
Known active fungal, bacterial, or viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required) |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
time from randomization to death |
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E.5.2 | Secondary end point(s) |
• PFS
• ORR
• DCR
• Time to first worsening of the mBPI-sf (Brief Pain Inventory Short Form Modified) “worst pain” score
• Duration of response
• Duration of disease control
• Safety and tolerability
• Pharmacokinetics (PK) and immunogenicity
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PFS is determined from the date of randomization and the date on which disease progresses or the date on which the patient dies, from any cause, whichever is earlier.
Response rates (ORR=CR+PR/Randomized subjects) (DCR=CR+PR+SD/Randomized subjects) will be based on evaluations done every 6 weeks until radiographic documentation of progression.
PRO: Day 1 of every cycle, Short-Term Follow-Up and Long-Term Follow-Up
DoR and duration of disease control is measured from the time measurement criteria are first met for CR or PR until the first date of objective progression is observed .
Safety and tolerability: On study treatment, Short-Term Follow-Up and Long-Term Follow-Up
PK and immunogenicity: At various time points according to the protocol and in the event of IRR
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Denmark |
Finland |
France |
Germany |
Hungary |
Israel |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
Poland |
Russian Federation |
Spain |
Sweden |
Switzerland |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 48 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 48 |