A Multicenter Phase II Clinical Trial of Neoadjuvant Trabectedin (YONDELIS®) in Patients with Localized Myxoid / Round Cell Liposarcoma

• Conditions: ocally advanced (Stage III) myxoid / round cell liposarcoma previously untreated with chemotherapy or radiation; MedDRA version: 9.1Level: LLTClassification code 10024630Term: Liposarcoma non-metastatic

• Registration Number: EUCTR2007-000035-25-DE
• Lead Sponsor: Pharma Mar, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-07-04
• Last Update Posted: 18 February 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

• Patient´s written informed consent before any study-specific procedure

• Adult patients (= 18 years)

• Pathological diagnosis of myxoid / round cell liposarcoma (MRCL) and availability of
pathology specimens for central review and pharmacogenomic studies

• Clinical evidence of locally advanced (Stage III), non-metastatic tumor, including
locally recurring disease after initial surgery

• Measurable disease (by RECIST)

• No prior chemotherapy or radiation (except for adjuvant post-operative
radiotherapy)

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
(appendix 1)

• Hematologic variables:
o Hemoglobin = 9 g/dL
o Absolute neutrophil count (ANC) = 1,500/µL, and
o Platelet count = 100,000/µL

• Serum creatinine < 1.5 mg/dL or creatinine clearance > 30 mL/min

• Creatinine phosphokinase (CPK) < 2.5 ULN

• Hepatic function variables:
o Total bilirubin < ULN
o Total alkaline phosphatase < 2.5 ULN, or if > 2.5 ULN consider alkaline
phosphatase liver fraction or GGT or 5’ nucleotidase must be < ULN
o AST (serum aspartate transaminase [SGOT]) and ALT (serum alanine
transaminase [SGPT]) must be <2.5 x ULN

• Albumin > 25 g/L
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Known hypersensitivity to any of the components of the trabectedin i.v.
formulation or dexamethasone

• Pregnant or lactating women or men and women of reproductive potential who are not using effective contraceptive methods (one or more of the following):
- Complete abstinence from intercourse from 2 weeks prior to administration of the
study drug, throughout the study, and for at least 6 months after completion or
premature discontinuation from the study to account for elimination of the
investigational drug; or,
- Patient or patient’s partner physical sterilization; or,
- One of the following, for female patients or female partner of male patients:
o Implants of levonorgestrel; or,
o Injectable progestogen; or,
o Oral contraceptive (combined or progestogen only; subject taking oral
contraceptives should have been on a stable regimen for at least 2 months
prior to screening),or,
o Any intrauterine device (IUD) with published data showing that the lowest
expected failure rate is less than 1% per year (not all IUDs meet this
criterion); or,
o Double barrier method (2 physical barriers or 1 physical barrier plus
spermicide); or,
o Any other method with published data showing that the lowest expected
failure rate for that method is less than 1% per year.

• History of another neoplastic disease (except basal cell carcinoma or cervical
carcinoma in situ adequately treated) unless in remission for 5 years or longer

• Known distant metastases

• Other serious illnesses such as congestive heart failure or angina pectoris,
myocardial infarction within 1 year before enrollment, uncontrolled arterial
hypertension or arrhythmias

• Psychiatric disorder that prevents compliance with protocol

• Active viral hepatitis or chronic liver disease

• Active infection

• Any other unstable medical condition

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: - To determine the pathological complete response (pCR) rate with trabectedin in <br> patients with locally advanced (Stage III) myxoid / round cell liposarcoma (MRCL). ;Secondary Objective: - Evaluate the objective response rate by RECIST and contrast such response with<br> changes in radiological density and tumor pathology<br><br>- Describe the incidence and severity of adverse events in this patient population<br><br>- Exploratory, hypothesis-generating pharmacogenomic analyses to correlate <br> molecular parameters in patient samples with clinical outcomes (pCR);Primary end point(s): Pathological Complete Response (pCR rate)