- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01876043
Efficacy and Safety of Plitidepsin in Patients With Advanced Unresectable or Metastatic, Relapsed/Refractory, Dedifferentiated Liposarcoma (DLPS): an Exploratory Phase II Multicenter Trial (APLIPO)
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
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Lille, France, 59020
- Centre Oscar Lambret
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Lyon, France, 69373
- Centre Léon Bérard
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Marseille, France, 13385
- Hôpital de la Timone
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Paris, France, 75005
- Institut Curie
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Toulouse, France, 31052
- Institut Claudius Regaud
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Villejuif, France, 94800
- Institut Gustave Roussy
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Voluntarily signed and dated written informed consent prior to any study specific procedure.
- Histologically confirmed DLPS by central review.
- Metastatic or unresectable locally advanced disease
- 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
- At least one prior anthracycline-containing chemotherapy regimen
- Age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1.
- Measurable disease according to RECIST v1.1 outside any previously irradiated field.
Adequate hematological, renal, metabolic and hepatic function.
- 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.
- 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).
- Total bilirubin 1.5 x ULN.
- Albumin > 25 g/l.
- Calculated creatinine clearance (CrCl) ≥ 40 ml/min (according to cockroft and Gault formula).
- Creatine phosphokinase (CPK) ≤ 2.5 x ULN.
- Troponin I ≤ ULN
- 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.
- 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.
- 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).
- Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or multiple gated acquisition (MUGA) within normal limits.
- 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.
- Patients with a french social security in compliance with the French law relating to biomedical research
Exclusion Criteria:
- Previous treatment with plitidepsin.
- More than three prior lines of therapy for advanced disease.
Concomitant diseases/conditions:
- 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.
- Previous mediastinal radiotherapy.
- Previous treatment with anthracyclines at cumulative doses in excess of 450 mg/m2 doxorubicin equivalent.
- Symptomatic arrhythmia or any arrhythmia requiring ongoing treatment, and/or prolonged QT-QTc grade > 1.
- Active uncontrolled infection.
- Myopathy or persistent CPK elevations > 2.5 x ULN in two different determinations performed with one week apart.
- Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
- Evidence of progressive or symptomatic central nervous system (CNS) or leptomeningeal metastases.
- 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.
- Tumor tissue sample not available for pathological review and/or JNK immunochemistry testing.
- Participation in a clinical study and / or receipt of an investigational drug during the last 30 days.
- Previous enrolment in the present study.
- Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons.
- Known hypersensitivity to any involved study drug or any of its formulation components
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: plitidepsin
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Patients received plitidepsin as an i.v. 3-h infusion of 5 mg/m2/day on days 1 and 15 every 4 weeks. Patients discontinued plitidepsin if one of the following occurred: consent withdrawal, unacceptable toxicity, disease progression (RECIST v1.1), intercurrent illness or investigator's decision. Single-arm phase II clinical trial based on a two-stage optimal Simon's design with 37 evaluable patients (first stage: 17 patients) used to distinguish a favorable true non-progression rate of 40% from a null rate of 20% (90% power and 10% type I error).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Patients Remaining Alive and Progression Free at 3 Months (i.e. Week 12 ± 1) as Per RECIST1.1 (PFS3).
Time Frame: 3 months
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Progression is defined using New Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), or a unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.
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3 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Patients With Objective Response at Six Months (as Per RECIST v1.1)
Time Frame: 6 months
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Objective response assessed as per New Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) : Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.;
Overall Response (OR) = CR + PR.
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6 months
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Percentage of Patients Remaining Alive and Progression Free at 6 Months as Per RECIST1.1.
Time Frame: 6 months
|
Progression is defined using New Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study), or a unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.
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6 months
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Progression-free Survival
Time Frame: from start of study treatment to the end of the study (up to 10 months)
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Progression-free survival is defined as the delay between the start date of treatment and the date of progression or death (from any cause), whichever occurs first.
Patients alive and progression free were censored at the date of last follow-up, death, or last patient contact.
Progression is assessed as per RECIST v1.1.
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from start of study treatment to the end of the study (up to 10 months)
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1-year Overall Survival (OS) Rate
Time Frame: 1 year
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1 year
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Treatment Safety (AEs, SAEs and Laboratory Abnormalities) Graded According to the NCI-CTCAE Version 4.0.
Time Frame: through study completion, an average of 1 year
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Toxicity were graded according to the NCI-CTCAE version 4.0.
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through study completion, an average of 1 year
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Number of Participants With a Biomarker Amplification
Time Frame: through study completion, an average of 1 year
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Genomic status of biomarkers obtained by using array-comparative genomic hybridization.
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through study completion, an average of 1 year
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Antoine Italiano, MD, Institut Bergonié
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IB2011-02
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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