Olaratumab Plus Trabectedin in Advanced Soft-tissue Sarcoma Patients Soft-tissue Sarcoma Patients

NCT03985722 | Unknown Phase 1

• 2 other identifiers: GEIS 582017-004771-32
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Phase I, multicentre clinical trial of olaratumab plus trabectedin in patients with advanced soft-tissue sarcoma. Olaratumab plus trabectedin could be synergistic and with a manageable toxicity profile in advanced STS. The study is a phase I, non-randomised, one-armed, multicenter trial, open-label. The dose escalation rules include patients in blocks of 3 o 6 patient. Treatment is a combination of unlimited cycles of oralatumab and trabectedin. Primary clinical study endpoint of phase I: \- Determine the maximum tolerated dose (MTD) or the recommended dose of olaratumab combined with trabectedin in advanced soft tissue sarcoma Secondary clinical study endpoints:

• Objective Response Rate (ORR): ORR is defined as the number of subjects with a Best Overall Response (BOR) according to RECIST 1.1.
• Progression free survival (PFS): time to progression or death from treatment initiation.
• Overall survival (OS): Time from treatment initiation until death. Efficacy measured through tumor response according to Choi criteria. The evaluation criteria will be based on the identification of target lesions in baseline and their follow-up until tumor progression.
• Correlation of clinical outcome with translational biomarkers.
• Quality of life (QoL) measured per QLQ-C30 questionnaire of EORTC

Conditions

Sarcoma, Soft Tissue

Keywords

advanced soft-tissue sarcoma

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated dose (MTD) or the recommended dose for phase II of Olaratumab plus Trabectedin.

  There will be determined the security profile for each dose level.

  Recruitment duration: 18 months

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  During recruitment and follow-up (30 months)

• Progression free survival (PFS)

  During recruitment and follow-up (30 months)

• Overall survival (OS)

  During recruitment and follow-up (30 months)

• Efficacy as per Choi criteria

  During recruitment and follow-up (30 months)

• Correlation of clinical outcome with translational biomarkers (See Translational Section)

  During recruitment and follow-up (30 months)

Study Arms (1)

Unlimited cycles of Olaratumab and Trabectedin

EXPERIMENTAL

The study is a phase I, non-randomised, one-armed, multicenter trial, open-label,. The dose escalation rules include patients in blocks of 3 o 6 patient. Treatment is a combination of unlimited cycles of oralatumab and trabectedin.

Drug: Olaratumab and Trabectedin

Interventions

Olaratumab and Trabectedin DRUG

Dose escalation levels: LEVEL -1: Olaratumab 15 mg/Kg D1 and D8 + Trabectedin 0.9 mg/m2 D1 This is a security level in case level 0 causes DLT. LEVEL 0\*: Olaratumab 15 mg/Kg D1 and D8 + Trabectedin 1.1 mg/m2 D1. \* Dose starting level is 0. LEVEL 1: Olaratumab 15 mg/Kg D1 and D8 + Trabectedin 1.3 mg/m2 D1. LEVEL 2: Olaratumab 15 mg/Kg D1 and D8 + Trabectedin 1.5 mg/m2 D1. LEVEL 3\*\*: Olaratumab 20 mg/kg C1D1 and C1D8 (induction) + Trabectedin 1.5 mg/m2 D1 and Olaratumab 15 mg/kg D1 and D8 (maintenance) + Trabectedin 1.5 mg/m2 D1 \*\*In LEVEL 3, Olaratumab dose of 20 mg/kg will be considered only for the first 2 doses (as induction doses, cycle 1 days 1 and 8). Then, the maintenance dose will be 15 mg/m2 for the rest of cycles.

Also known as: Lartruvo and Yondelis

Unlimited cycles of Olaratumab and Trabectedin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must provide written informed consent prior to performance of study specific procedures and must be willing to comply with treatment and follow-up.
• Age: 18-80 years.
• Histologic diagnosis of soft tissue sarcoma: liposarcoma (dedifferentiated and myxoid/round cell), leiomyosarcoma, undifferentiated pleomorphic sarcoma, synovial sarcoma confirmed, before enrolment confirmation, by central pathology review by a paraffin embedded tumor tissue.
• Metastatic/advanced disease in progression in the last 6 months.
• Patients had previously received at least anthracyclines if clinically indicated.
• Previous olaratumab administration is allowed.
• Measurable disease according to RECIST 1.1 criteria.
• ECOG Performance Status of 0-1.
• Adequate hepatic, renal, cardiac, and hematologic function.
• Laboratory tests as follows: Haemoglobin \>9g/dl, Absolute neutrophil count ≥ 1,500/mm³, Platelet count ≥ 100,000/mm³, Total Bilirubin ≤ 1.5 mg/dL, PT≤ 1.5 ULN and INR ≤ 1.5, AST and ALT ≤ 2.5 times upper limit of normal, Creatinine
• ≤ 1.5 mg/dL Calcium ≤ 12 mg/dL and Blood glucose \< 150 mg/dL, Urine protein assessment: \<2+, and/or \<3.5g protein/24h.
• Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan.
• Having a central venous portal is mandatory before treatment initiation.
• Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment. Females of child-bearing potential and males and must agree to use highly effective contraceptive precautions during the trial and up to 6 months following the last dose of study drug. A highly effective method of birth control is defined as one that results in a low failure rate (that is, \<1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine contraceptive devices (IUDs), sexual abstinence, or a vasectomized partner.
• Exceptions: Females not of child-bearing potential due to surgical sterilization (at least 6 weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history or menopause. A "postmenopausal woman" is a woman meeting either of the following criteria:

You may not qualify if:

• More than 2 previous lines of chemotherapy for advanced disease. Previous trabectedin not allowed.
• Hipersensitivity to olaratumab.
• The following histologies are not included: Ewing Sarcoma, extraskeletal osteosarcoma, extraskeletal myxoid chondrosarcoma, Kaposi's sarcoma, rhabdomyosarcoma and gastrointestinal stromal tumor (GIST).
• Uncontrolled intercurrent illness including (not limited to): symptomatic congestive heart failure (CHF) (New York Heart Association \[NYHA\] III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks prior to registration, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI-CTCAE\] version 5.0 Grade \>= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (\>= Grade 3).
• Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
• Other disease or illness within the past 6 months, including any of the following:
• Myocardial infarction
• Coronary or peripheral artery bypass graft
• Cerebrovascular accident or transient ischemic attack
• Pulmonary embolism
• The patient has electively planned or will require major surgery during the course of the study
• Social situation that would preclude study compliance.
• Prolonged QTc interval (i.e., QTc \> 450 msec for males or QTc \> 470 msec for females) on baseline ECG.
• Hemorrhage ≥ Grade 3 in the past 4 weeks.
• Females who are pregnant or breast-feeding.

Sponsors & Collaborators

• Grupo Espanol de Investigacion en Sarcomas: lead

Study Sites (1)

GEIS

Madrid, 28006, Spain

Location

MeSH Terms

Conditions

Sarcoma

Interventions

olaratumab; Trabectedin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Javier MARTIN-BROTO, MD

  University Hospital "Fundación Jiménez Díaz"

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is a phase I, non-randomised, one-armed, multicenter trial, open-label. The dose escalation rules include patients in blocks of 3 o 6 patient. Treatment is a combination of unlimited cycles of oralatumab and trabectedin.

Study Record Dates

• First Submitted: May 30, 2019
• First Posted: June 14, 2019
• Study Start: September 21, 2018
• Primary Completion: February 17, 2021
• Study Completion: May 5, 2024
• Last Updated: March 27, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)