Efficacy Study on Trabectedin in Retroperitoneal Leiomyosarcoma and Well Differentiated/Dedifferentiated Liposarcoma

Leiomyosarcoma Clinical Trial

— TRAVELL  

Official title:

A Phase II Study on Trabectedin in Advanced Retroperitoneal Leiomyosarcoma and Well Differentiated/Dedifferentiated Liposarcoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02247544
• Other study ID #: ISG-STS-TRAB-2012
• Secondary ID: 2012-005428-14
• Status: Completed
• Phase: Phase 2
• Start date: March 2014
• Est. completion date: March 12, 2019

Study information

• Verified date: October 2021
• Source: Italian Sarcoma Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an Italian, multicentre, single arm, phase II study, with an intra-patient comparison end point. This study aims at confirming the activity of the drug trabectedin as second/further line treatment in retroperitoneal leiomyosarcoma and well differentiated/dedifferentiated liposarcoma expressed in terms of slowing down tumour growth. Another objective is to investigate this peculiar benefit of trabectedin in typical retroperitoneal sarcomas may be exploited to help multidisciplinary clinical decision-making in the management of retroperitoneal sarcomas

Description:

Retroperitoneal soft-tissue sarcomas (R-STSs) are rare neoplasms, accounting for 10% to 15% of Soft Tissue Sarcomas (STSs), which represent 1-3% of all cancers. They may show different histological types, but the predominant ones in the retroperitoneal region are: leiomyosarcoma, liposarcoma. The most commonly encountered in the retroperitoneum is the well differentiated/dedifferentiated liposarcoma. First-line chemotherapy usually consists of doxorubicin and/or ifosfamide. These two drugs are the most active agents in adult STSs, with a dose-response relationship and response rates between 20% and 50%. However, the sarcoma community is currently doubtful as to the activity of ifosfamide in the subgroup of leiomyosarcomas. Trabectedin has been found to be mainly active in leiomyosarcoma and liposarcoma and is approved by European Medicines Agency (EMA) as second-line chemotherapy for STSs. Although the response rate observed in pre-registration studies did not exceed 10%, trabectedin provided disease control, with progression arrest rates exceeding 50% and Progression Free Survival (PFS) rates exceeding 20% at 6 months. Since so far no phase II studies tested the activity of trabectedin in retroperitoneal sarcomas, this is the specific aim of this study. Target population: Patients with previously treated, histologically confirmed, retroperitoneal leiomyosarcoma and well differentiated/dedifferentiated liposarcoma. Patients may be either unamenable to surgery or amenable but in whom the addition of medical treatment is considered clinically advisable. Translational studies will be performed, with the aim of characterising the tumour biological features associated with different response patterns to trabectedin. These assessments will be done in 15-20 patients who will undergo surgery after trabectedin, comparing tumour tissue specimens collected before and after treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: March 12, 2019
• Est. primary completion date: March 12, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Persistent or locally relapsed and/or metastatic disease (in case of local disease, surgery may be technically feasible or not, but the clinical judgment must be that medical therapy is indicated)
• Pathology specimens available for centralized review
• Age = 18 years
• European Eastern Cooperative Oncology Group Personal Status (ECOG PS) = 2
• One or more previous systemic treatments employing anthracyclines and ifosfamide (unless one or both are clinically contraindicated)
• Measurable disease, as defined by Response Evaluation Criteria In Solid Tumors (RECIST)
• A minimum of 3 weeks since any previous medical therapy
• Recovery from toxic effects of prior therapies to National Cancer Institute Common Toxicity Criteria (NCI CTC) Grade 1 or lower
• Adequate haematological, renal and liver functions
• Ability and willingness to provide informed consent

Exclusion Criteria:

• Pregnant or breast-feeding women
• Prior exposure to trabectedin
• Peripheral neuropathy, Grade 2 or higher
• History of other malignancies (except for basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission for 5 years or more and judged of negligible potential of relapse
• Known central nervous system (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

Related Conditions & MeSH terms

• Leiomyosarcoma
• Liposarcoma

Intervention

Drug:
• Trabectedin
Trabectedin administered at a dose of 1.5 mg/m2 - 1.3 mg/m2 (at investigator's discretion, with a top-dose of 2.6 total mg per cycle) as a 24-hour continuous infusion via a central venous access until progressive disease, major toxicity, patient's intolerance, unwillingness to continue treatment, or medical decision by the responsible physician

Locations

Country	Name	City	State
Italy	Centro di Riferimento Oncologico di Aviano	Aviano	PD
Italy	Istituto Tumori Giovanni Paolo II	Bari	BA
Italy	Azienda Ospedaliera Giovanni Paolo XXIII	Bergamo	BG
Italy	Azienda Ospedaliera S. Orsola-Malpighi	Bologna	BO
Italy	A.O. Spedali Civili	Brescia	BS
Italy	Ospedale Oncologico A. Businco	Cagliari	CA
Italy	Istituto per la Ricerca e la Cura del Cancro di Candiolo	Candiolo	TO
Italy	Azienda Ospedaliera Sant'Anna	Como	CO
Italy	Azienda Ospedaliera S Croce e Carle	Cuneo	CN
Italy	IRST IRCCS Meldola	Meldola	FC
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	MI
Italy	Istituto Europeo di Oncologia	Milano	MI
Italy	Istituto Nazionale Tumori - IRCCS - Fondazione Pascale	Napoli
Italy	Istituto Oncologico Veneto	Padova	PD
Italy	Azienda Ospedaliera Universitaria Paolo Giaccone	Palermo	PA
Italy	Azienda Ospedaliera Universitaria Santa Chiara	Pisa	PI
Italy	Ospedale Misericordia e Dolce	Prato	PO
Italy	Policlinico Universitario Campus Biomedico	Roma	RM
Italy	Istituto Clinico Humanitas	Rozzano	MI
Italy	Azienda Ospedaliera Santa Maria	Terni	TR
Italy	Ospedale Gradenigo	Torino	TO

Sponsors (2)

Lead Sponsor	Collaborator
Italian Sarcoma Group	Istituto Di Ricerche Farmacologiche Mario Negri

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Growth Modulation Rate	The primary end point of the study will be the proportion of responders to trabectedin, based on the ratio, in each single patient, between PFS under trabectedin (PFS) and time to progression after previous chemotherapy treatment (TTP1).	From date of randomization until progressive disease, assessed up to 48 months
Secondary	Objective response (OR) in the overall sample		From date of randomization until progressive disease, assessed up to 48 months
Secondary	Pathological tumour response in the two eligible histological types, in patients undergoing surgery after treatment		From date of randomization until the best tumour dimensional response, assessed up to 48 months
Secondary	PFS and OR in the two eligible histological types		From date of randomization until progressive disease, assessed up to 48 months
Secondary	PFS in patients who undergo surgery after, or during, medical therapy and those who do not		From date of randomization until progressive disease, assessed up to 48 months
Secondary	Number of patients with grade>=3 adverse drug reactions, number of serious adverse events related to study drug and number of patients who will experience at least one serious adverse event		From date of randomization until progressive disease, assessed up to 48 months
Secondary	Efficacy of trabectedin in reducing cancer related pain	All patients will be administered a standardized questionnaire evaluating cancer related pain and use of antalgic medication.	From date of randomization until progressive disease, assessed up to 48 months

External Links

•   On this website page physicians can find the complete list of Cytochrome P450 3A4 (CYP3A4) enzyme inducers/inhibitors which may alter the plasma concentrations of the trabectedin