Clinical trial NCT04394728: Pharmacometabolomic of Trabectedin in Soft Tissue Patients
Official title: Research of Serum and Urine Metabolomic Biomarkers Predictive Pharmacokinetic Parameters of Trabectidin in Patients With Soft Tissues Sarcomas
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sarcoma
Keywords: soft tissues sarcoma
Lead sponsor: Centro di Riferimento Oncologico - Aviano
Sponsor class: OTHER
First posted: 2020-05-19
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Soft tissue sarcoma patients with unresectable and/or metastatic disease

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.

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.

Eligibility criteria: Inclusion Criteria:

* Advanced Soft Tissues Sarcoma STSs (unresectable and/or metastatic disease).
* One previous systemic treatment with ananthracycline ± ifosfamide.
* Measurable disease, as defined by RECIST criteria.
* ECOG PS ≤2.
* Age ≥18 years.
* A minimum of 3 weeks since prior tumor directed therapy
* Recovery from toxic effects of prior therapies to NCI CTC Grade 1 or lower.
* Adequate haematological, renal liver function.
* Ability and willingness to provide informed consent

Exclusion Criteria:

* Pregnant or breast-feeding women
* Prior exposure to Trabectedin.
* Peripheral neuropathy, Grade 2 or higher.
* Known CNS metastases.
* Active viral hepatitis or chronic liver disease.
* Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within one year before enrolment, uncontrolled arterial hypertension or arrhythmias.
* Active major infection.
* Other serious concomitant illnesses.

Primary outcomes:
measure: Area Under Curve (AUC)
timeFrame: 0-48 hours
measure: Cmax
timeFrame: 0-48 hours
measure: Metabolomics profile
timeFrame: 0 hours ( pre-dose)
Secondary outcomes:
measure: Progression free survival
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
measure: Treatment Toxicity
timeFrame: through study completion, an average of 1 year
Other outcomes:
Locations:
Study officials:
affiliation: Centro di Riferimento Oncologico - Aviano
name: Gianmaria Miolo
role: PRINCIPAL_INVESTIGATOR
References: