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

Primary Purpose

Liposarcoma, Leiomyosarcoma

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Trabectedin
Sponsored by
Italian Sarcoma Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liposarcoma focused on measuring STS, leiomyosarcoma, liposarcoma, trabectedin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Istituto Tumori Giovanni Paolo II
  • Azienda Ospedaliera Giovanni Paolo XXIII
  • Azienda Ospedaliera S. Orsola-Malpighi
  • A.O. Spedali Civili
  • Ospedale Oncologico A. Businco
  • Azienda Ospedaliera S Croce e Carle
  • Azienda Ospedaliera Sant'Anna
  • IRST IRCCS Meldola
  • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Istituto Europeo di Oncologia
  • Istituto Clinico Humanitas
  • Azienda Ospedaliera Universitaria Paolo Giaccone
  • Centro di Riferimento Oncologico di Aviano
  • Istituto Oncologico Veneto
  • Azienda Ospedaliera Universitaria Santa Chiara
  • Ospedale Misericordia e Dolce
  • Policlinico Universitario Campus Biomedico
  • Istituto per la Ricerca e la Cura del Cancro di Candiolo
  • Ospedale Gradenigo
  • Azienda Ospedaliera Santa Maria
  • Istituto Nazionale Tumori - IRCCS - Fondazione Pascale

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Trabectedin

Arm Description

Trabectedin will be administered intravenously at a dose of 1.5 mg/m2 or 1.3 mg/m2 (at investigator's discretion, with a top-dose of 2.6 total mg per cycle) as a 24-hour infusion once every 3 weeks (cycle day 1). Since trabectedin has no cumulative toxicities, treatment can be continued until progressive disease, major toxicity, patient's intolerance or unwillingness to continue treatment or medical decision by the responsible physician. In the subgroup of patients amenable to surgery, treatment will be reasonably continued until the best dimensional response.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Objective response (OR) in the overall sample
Pathological tumour response in the two eligible histological types, in patients undergoing surgery after treatment
PFS and OR in the two eligible histological types
PFS in patients who undergo surgery after, or during, medical therapy and those who do not
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
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.

Full Information

First Posted
September 5, 2014
Last Updated
October 29, 2021
Sponsor
Italian Sarcoma Group
Collaborators
Istituto Di Ricerche Farmacologiche Mario Negri
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1. Study Identification

Unique Protocol Identification Number
NCT02247544
Brief Title
Efficacy Study on Trabectedin in Retroperitoneal Leiomyosarcoma and Well Differentiated/Dedifferentiated Liposarcoma
Acronym
TRAVELL
Official Title
A Phase II Study on Trabectedin in Advanced Retroperitoneal Leiomyosarcoma and Well Differentiated/Dedifferentiated Liposarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
March 2014 (undefined)
Primary Completion Date
March 12, 2019 (Actual)
Study Completion Date
March 12, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Italian Sarcoma Group
Collaborators
Istituto Di Ricerche Farmacologiche Mario Negri

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liposarcoma, Leiomyosarcoma
Keywords
STS, leiomyosarcoma, liposarcoma, trabectedin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
105 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Trabectedin
Arm Type
Experimental
Arm Description
Trabectedin will be administered intravenously at a dose of 1.5 mg/m2 or 1.3 mg/m2 (at investigator's discretion, with a top-dose of 2.6 total mg per cycle) as a 24-hour infusion once every 3 weeks (cycle day 1). Since trabectedin has no cumulative toxicities, treatment can be continued until progressive disease, major toxicity, patient's intolerance or unwillingness to continue treatment or medical decision by the responsible physician. In the subgroup of patients amenable to surgery, treatment will be reasonably continued until the best dimensional response.
Intervention Type
Drug
Intervention Name(s)
Trabectedin
Other Intervention Name(s)
Yondelis
Intervention Description
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
Primary Outcome Measure Information:
Title
Growth Modulation Rate
Description
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).
Time Frame
From date of randomization until progressive disease, assessed up to 48 months
Secondary Outcome Measure Information:
Title
Objective response (OR) in the overall sample
Time Frame
From date of randomization until progressive disease, assessed up to 48 months
Title
Pathological tumour response in the two eligible histological types, in patients undergoing surgery after treatment
Time Frame
From date of randomization until the best tumour dimensional response, assessed up to 48 months
Title
PFS and OR in the two eligible histological types
Time Frame
From date of randomization until progressive disease, assessed up to 48 months
Title
PFS in patients who undergo surgery after, or during, medical therapy and those who do not
Time Frame
From date of randomization until progressive disease, assessed up to 48 months
Title
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
Time Frame
From date of randomization until progressive disease, assessed up to 48 months
Title
Efficacy of trabectedin in reducing cancer related pain
Description
All patients will be administered a standardized questionnaire evaluating cancer related pain and use of antalgic medication.
Time Frame
From date of randomization until progressive disease, assessed up to 48 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paolo G. Casali, MD
Organizational Affiliation
IRCCS Fondazione Istituto Nazionale per la cura dei tumori di Milano
Official's Role
Principal Investigator
Facility Information:
Facility Name
Istituto Tumori Giovanni Paolo II
City
Bari
State/Province
BA
ZIP/Postal Code
70124
Country
Italy
Facility Name
Azienda Ospedaliera Giovanni Paolo XXIII
City
Bergamo
State/Province
BG
ZIP/Postal Code
24127
Country
Italy
Facility Name
Azienda Ospedaliera S. Orsola-Malpighi
City
Bologna
State/Province
BO
ZIP/Postal Code
40138
Country
Italy
Facility Name
A.O. Spedali Civili
City
Brescia
State/Province
BS
ZIP/Postal Code
25123
Country
Italy
Facility Name
Ospedale Oncologico A. Businco
City
Cagliari
State/Province
CA
ZIP/Postal Code
09122
Country
Italy
Facility Name
Azienda Ospedaliera S Croce e Carle
City
Cuneo
State/Province
CN
ZIP/Postal Code
12100
Country
Italy
Facility Name
Azienda Ospedaliera Sant'Anna
City
Como
State/Province
CO
ZIP/Postal Code
22020
Country
Italy
Facility Name
IRST IRCCS Meldola
City
Meldola
State/Province
FC
ZIP/Postal Code
47014
Country
Italy
Facility Name
Fondazione IRCCS Istituto Nazionale dei Tumori
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy
Facility Name
Istituto Europeo di Oncologia
City
Milano
State/Province
MI
ZIP/Postal Code
20141
Country
Italy
Facility Name
Istituto Clinico Humanitas
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Paolo Giaccone
City
Palermo
State/Province
PA
ZIP/Postal Code
90127
Country
Italy
Facility Name
Centro di Riferimento Oncologico di Aviano
City
Aviano
State/Province
PD
ZIP/Postal Code
33081
Country
Italy
Facility Name
Istituto Oncologico Veneto
City
Padova
State/Province
PD
ZIP/Postal Code
35128
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Santa Chiara
City
Pisa
State/Province
PI
ZIP/Postal Code
56124
Country
Italy
Facility Name
Ospedale Misericordia e Dolce
City
Prato
State/Province
PO
ZIP/Postal Code
59100
Country
Italy
Facility Name
Policlinico Universitario Campus Biomedico
City
Roma
State/Province
RM
ZIP/Postal Code
00128
Country
Italy
Facility Name
Istituto per la Ricerca e la Cura del Cancro di Candiolo
City
Candiolo
State/Province
TO
ZIP/Postal Code
10060
Country
Italy
Facility Name
Ospedale Gradenigo
City
Torino
State/Province
TO
ZIP/Postal Code
10153
Country
Italy
Facility Name
Azienda Ospedaliera Santa Maria
City
Terni
State/Province
TR
ZIP/Postal Code
05100
Country
Italy
Facility Name
Istituto Nazionale Tumori - IRCCS - Fondazione Pascale
City
Napoli
ZIP/Postal Code
80131
Country
Italy

12. IPD Sharing Statement

Links:
URL
http://medicine.iupui.edu/flockhart/table.htm
Description
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

Learn more about this trial

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

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