Metabol-STS: Pharmacometabolomic of Trabectedin in Soft Tissue Patients
Study Details
Study Description
Brief Summary
This perspective, mono institutional study is addressed to find potential serum and urine biomarkers predictive of the pharmacokinetic and pharmacodynamic profile of soft tissue sarcomas patients treated with trabectedin.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
Detailed Description
This investigation enrolled patients with unresectable and/or metastatic soft tissue sarcoma not responsive to the first-line treatment based on anthracycline/ifosfamide. Patients underwent trabectedin monotherapy that was administered intravenously at the dose of 1.3 mg/m2 every 21 days.
Single overnight fasting urine and blood samples were collected on day-1 of the first trabectedin administration.
Plasma pharmacokinetics was performed during cycle 1. Blood samples, drawn from a site separate from the drug infusion site, were obtained prior to the infusion (basal) at 2, 8, 24 (end of infusion) and 0.5, 1.0, 4.0, 8.0, 24.0 after the end of the infusion. Plasma concentrations of trabectedin were measured by liquid chromatography, tandem mass spectrometry assay (LC-MS/MS) and the pharmacokinetic parameters (Cmax, Clearance, AUC and T1/2) were calculated from the concentration-time curve using a non-compartmental model.
Metabolomics profiles were explored by LC-MS/MS in predose urine and serum and encompassed a total of 192: a) 45 amino acid derivatives, virtually involved in a wide set of biochemical pathways; b) 40 different acylcarnitines, principally involved in the cellular energy metabolism; c) 15 lysophosphatidylcholine metabolites, 77 phosphatidylcholine derivatives, and 15 sphingomyelins, involved in fatty acid metabolism and cellular signaling. The identification of predictive metabolomics biomarkers is performed using univariate and multivariate statistical analyses.
Study Design
Outcome Measures
Primary Outcome Measures
- Area Under Curve (AUC) [0-48 hours]
Pharmacokinetics profile of Trabectedin for 24 hours intravenous infusion
- Cmax [0-48 hours]
Maximum plasma concentration of Trabectedin
- Metabolomics profile [0 hours ( pre-dose)]
Predose metabolomic profile in serum and urine
Secondary Outcome Measures
- Progression free survival [2 years]
From the first day of treatment to progression or death due to any cause
- Overall survival [2 years]
The time from the first course of trabectedin to death from any cause or to the last follow-up
- Treatment Toxicity [through study completion, an average of 1 year]
Hematologic and non-hematologic toxicity according to WHO
Eligibility Criteria
Criteria
Inclusion Criteria:
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Advanced Soft Tissues Sarcoma STSs (unresectable and/or metastatic disease).
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One previous systemic treatment with ananthracycline ± ifosfamide.
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Measurable disease, as defined by RECIST criteria.
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ECOG PS ≤2.
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Age ≥18 years.
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A minimum of 3 weeks since prior tumor directed therapy
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Recovery from toxic effects of prior therapies to NCI CTC Grade 1 or lower.
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Adequate haematological, renal liver function.
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Ability and willingness to provide informed consent
Exclusion Criteria:
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Pregnant or breast-feeding women
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Prior exposure to Trabectedin.
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Peripheral neuropathy, Grade 2 or higher.
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Known CNS metastases.
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Active viral hepatitis or chronic liver disease.
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Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within one year before enrolment, uncontrolled arterial hypertension or arrhythmias.
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Active major infection.
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Other serious concomitant illnesses.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Centro di Riferimento Oncologico - Aviano
Investigators
- Principal Investigator: Gianmaria Miolo, Centro di Riferimento Oncologico - Aviano
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- CRO-2015-04