Efficacité et Tolérance de la Plitidepsine chez les patients souffrant d’un liposarcome dédifférencié (DLPS) avancé, non opérable ou métastatique, en rechute/réfractaire : Une étude exploratoire multicentrique de phase II.

• Conditions: DEDIFFERENTIATED LIPOSARCOMA (DLPS); MedDRA version: 9.1Level: PTClassification code 10024627Term: Liposarcoma

• Registration Number: EUCTR2009-010980-18-FR
• Lead Sponsor: Pharma Mar, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-05-19
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

1. Histologically confirmed DLPS.
2. Metastatic or unresectable locally advanced disease with progression or relapse after standard therapy (at least one prior anthracycline-containing chemotherapy regimen).
3. Age = 18 years.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 1.
5. Documented disease progression (as per RECIST) before study entry.
6. Measurable disease according to RECIST outside any previously irradiated field.
7. Adequate hematological, renal, metabolic and hepatic function.
a. Hemoglobin = 9 g/dl (patients may have received prior red blood cell [RBC] transfusion, if clinically indicated); absolute neutrophil count (ANC) = 1.2 x 109/l, and platelet count = 100 x 109/l.
b. Alkaline phosphatase(AP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =2.5 x upper limit of normality (ULN) (=5 in case of extensive skeletal involvement for AP exclusively).
c. Total bilirubin = 1.5 x ULN. d. Albumin > 25 g/l.
e. Calculated creatinine clearance (CrCl) = 40 ml/min (according to Cockroft and Gault formula).
f. Creatine phosphokinase (CPK) = 2.5 x ULN.
8. Troponin I = ULN.
9. No prior or concurrent malignant disease except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma.
10. Life expectancy > 3 months.
11. At least three weeks since last chemotherapy (six weeks in case of nitrosoureas and mitomycin C), immunotherapy or any other pharmacological treatment and/or radiotherapy.
12. Recovery to grade = 1 from any adverse event (AE) derived from previous treatment (excluding alopecia of any grade and non-painful peripheral neuropathy grade = 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 3.0).
13. Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or multiple gated acquisition (MUGA) within normal limits.
14. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six months after discontinuation of treatment. Acceptable methods of contraception include intrauterine device (IUD), oral contraceptive, subdermal implant and double barrier.
15. Voluntarily signed and dated written informed consents prior to any study specific procedure.
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

1. Previous treatment with plitidepsin.
2. Pathological diagnosis different from DLPS.
3. More than three prior lines of therapy for advanced disease.
4. Concomitant diseases/conditions:
a. History or presence of unstable angina, myocardial infarction, congestive heart failure or clinically significant valvular heart disease.
b. Previous mediastinal radiotherapy.
c. Previous treatment with anthracyclines at cumulative doses in excess of 450 mg/m2 doxorubicin equivalent.
d. Symptomatic arrhythmia or any arrhythmia requiring ongoing treatment, and/or prolonged QT-QTc grade > 1.
e. Active uncontrolled infection.
f. Myopathy or persistent CPK elevations > 2.5 x ULN in two different determinations performed with one week apart.
g. Limitation of the patient’s ability to comply with the treatment or to follow-up the protocol.
h. Any other major illness that, in the Investigator’s judgment, will substantially increase the risk associated with the patient’s participation in this study.
5. Evidence of progressive or symptomatic central nervous system (CNS) or leptomeningeal metastases.
6. Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding. 7. Treatment with any investigational product within the period = 5 half-lives prior to the first infusion of plitidepsin.
8. Tumor tissue sample not available for pathological review and/or JNK immunochemistry testing.

Study & Design

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