Pharmacometabolomic of Trabectedin in Soft Tissue Patients (Metabol-STS)

Research of Serum and Urine Metabolomic Biomarkers Predictive Pharmacokinetic Parameters of Trabectidin in Patients With Soft Tissues Sarcomas

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.

Study Overview

• Status: Completed
• Conditions: Sarcoma
• Intervention / Treatment: Drug: 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.

• Study Type: Observational
• Enrollment (Actual): 44

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Soft tissue sarcoma patients with unresectable and/or metastatic disease

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under Curve (AUC)	Pharmacokinetics profile of Trabectedin for 24 hours intravenous infusion	0-48 hours
Cmax	Maximum plasma concentration of Trabectedin	0-48 hours
Metabolomics profile	Predose metabolomic profile in serum and urine	0 hours ( pre-dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	From the first day of treatment to progression or death due to any cause	2 years
Overall survival	The time from the first course of trabectedin to death from any cause or to the last follow-up	2 years
Treatment Toxicity	Hematologic and non-hematologic toxicity according to WHO	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Centro di Riferimento Oncologico - Aviano
• Investigators: Principal Investigator: Gianmaria Miolo, Centro di Riferimento Oncologico - Aviano

Publications and helpful links

Helpful Links

• Pharmaco-metabolomics: An Emerging "Omics" Tool for the Personalization of Anticancer Treatments and Identification of New Valuable Therapeutic Targets

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): January 1, 2020
• Study Completion (Actual): January 1, 2020

Study Registration Dates

• First Submitted: May 6, 2020
• First Submitted That Met QC Criteria: May 15, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Actual): May 19, 2020
• Last Update Submitted That Met QC Criteria: May 15, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: soft tissues sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Trabectedin
• Other Study ID Numbers: CRO-2015-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No