Trial record 4 of 9 for:    aplidine

Efficacy and Safety of Plitidepsin in Patients With Advanced Unresectable or Metastatic, Relapsed/Refractory, Dedifferentiated Liposarcoma (DLPS): an Exploratory Phase II Multicenter Trial (APLIPO)

This study has been terminated.
Sponsor:
Collaborators:
Ministry of Health, France
PharmaMar
Information provided by (Responsible Party):
Institut Bergonié
ClinicalTrials.gov Identifier:
NCT01876043
First received: October 29, 2012
Last updated: July 25, 2013
Last verified: December 2012
  Purpose

Liposarcomas are soft tissue sarcomas most frequent. We distinguish three subtypes on the basis of their histological and cytogenetic characteristics: well-differentiated liposarcoma / dedifferentiated, myxoid liposarcoma and / or round cell liposarcoma and pleomorphic. Dedifferentiated liposarcomas (LDD) represent 20% of liposarcomas and are characterized by well-differentiated component associated with a contingent sarcomatous differentiation and fat-usually high grade. The LDD are most often rétropértionéal seat. Thus, their development is very long asymptomatic. At diagnosis, tumor volume is often very important making surgical removal impossible in a high proportion of cases. Operable tumors have also a risk of local recurrence by about 50% and about 20% metastatic. Chemotherapy is the only treatment of these advanced forms. However, the currently available drugs (adriamycin, ifosfamide) have only very limited effectiveness. Progression-free survival of patients does not exceed 2 months. The LDD is characterized cytogenetically by the constant presence of two amplicons (1p32 and 6q23) respectively targeting genes MAP3K5 and JUN. These two genes encode proteins involved in the signaling pathway Jun N-terminal kinase (JNK). Activation of JNK is involved in the loss of adipose differentiation and tumor aggressiveness of LDD. The plitidepsin is a drug capable of inducing apoptosis of tumor cells carrying a functional activation of the JNK pathway. This drug has such a pro-apoptotic and anti-proliferative in vitro models of LDD. plitidepsin could represent the treatment of choice for patients with advanced LDD. The objective of this study is to evaluate the anti-tumor activity of plitidepsin patients with locally advanced dedifferentiated liposarcomas and / or metastatic.


Condition Intervention Phase
Adult Patients With Unresectable Locally Advanced or Metastatic, Relapsed/Refractory Dedifferentiated Liposarcoma
Drug: plitidepsin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Plitidepsin in Patients With Advanced Unresectable or Metastatic, Relapsed/Refractory, Dedifferentiated Liposarcoma (DLPS): an Exploratory Phase II Multicenter Trial

Resource links provided by NLM:


Further study details as provided by Institut Bergonié:

Primary Outcome Measures:
  • To evaluate the antitumor activity of plitidepsin in terms of non-progression rate at three months (PFS3). [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response rate (ORR) at six months [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Non-progression rate at six months [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • 1-year progression-free survival rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • 1-year overall survival (OS) rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Treatment safety (AEs, SAEs and laboratory abnormalities) graded according to the NCI-CTCAE version 4.0. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Pharmacogenomic (PGx) analysis of predictive markers of treatment outcome from pre-treatment available paraffin-embedded tumor tissue samples [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: February 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: plitidepsin
plitidepsin
Drug: plitidepsin

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Voluntarily signed and dated written informed consent prior to any study specific procedure.
  2. Histologically confirmed DLPS by central review.
  3. Metastatic or unresectable locally advanced disease
  4. Progressive disease according to RECIST v1.1 criteria diagnosed on the basis of two CT scan obtained at an interval less than 3 months and confirmed by central review
  5. At least one prior anthracycline-containing chemotherapy regimen
  6. Age ≥ 18 years.
  7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.
  8. Measurable disease according to RECIST v1.1 outside any previously irradiated field.
  9. Adequate hematological, renal, metabolic and hepatic function.

    1. 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.
    2. 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).
    3. Total bilirubin 1.5 x ULN.
    4. Albumin > 25 g/l.
    5. Calculated creatinine clearance (CrCl) ≥ 40 ml/min (according to cockroft and Gault formula).
    6. Creatine phosphokinase (CPK) ≤ 2.5 x ULN.
  10. Troponin I ≤ ULN
  11. No prior or concurrent malignant disease in the last 5 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma.
  12. 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.
  13. 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 4.0).
  14. Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or multiple gated acquisition (MUGA) within normal limits.
  15. 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.
  16. Patients with a french social security in compliance with the French law relating to biomedical research

Exclusion Criteria:

  1. Previous treatment with plitidepsin.
  2. More than three prior lines of therapy for advanced disease.
  3. Concomitant diseases/conditions:

    1. History or presence of unstable angina, myocardial infarction, congestive heart failure or clinically significant valvular heart disease. Symptomatic arrhythmia or any arrhythmia requiring ongoing treatment, and/or prolonged QT-QTc grade > 1.
    2. Previous mediastinal radiotherapy.
    3. Previous treatment with anthracyclines at cumulative doses in excess of 450 mg/m2 doxorubicin equivalent.
    4. Symptomatic arrhythmia or any arrhythmia requiring ongoing treatment, and/or prolonged QT-QTc grade > 1.
    5. Active uncontrolled infection.
    6. Myopathy or persistent CPK elevations > 2.5 x ULN in two different determinations performed with one week apart.
    7. Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
  4. Evidence of progressive or symptomatic central nervous system (CNS) or leptomeningeal metastases.
  5. 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.
  6. Tumor tissue sample not available for pathological review and/or JNK immunochemistry testing.
  7. Participation in a clinical study and / or receipt of an investigational drug during the last 30 days.
  8. Previous enrolment in the present study.
  9. Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons.
  10. Known hypersensitivity to any involved study drug or any of its formulation components
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01876043

Locations
France
Centre Oscar Lambret
Lille, France, 59020
Centre Léon Bérard
Lyon, France, 69373
Hôpital de la Timone
Marseille, France, 13385
Institut Curie
Paris, France, 75005
Institut Claudius Regaud
Toulouse, France, 31052
Institut Gustave Roussy
Villejuif, France, 94800
Sponsors and Collaborators
Institut Bergonié
Ministry of Health, France
PharmaMar
Investigators
Study Chair: Antoine Italiano, MD Institut Bergonié
  More Information

Additional Information:
No publications provided

Responsible Party: Institut Bergonié
ClinicalTrials.gov Identifier: NCT01876043     History of Changes
Other Study ID Numbers: IB2011-02
Study First Received: October 29, 2012
Last Updated: July 25, 2013
Health Authority: France : Agence Française de Sécurité Sanitaire des Produits de Santé

Additional relevant MeSH terms:
Liposarcoma
Neoplasms, Adipose Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma

ClinicalTrials.gov processed this record on April 22, 2014