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

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ClinicalTrials.gov Identifier: NCT02247544
Recruitment Status : Completed
First Posted : September 25, 2014
Last Update Posted : May 10, 2019
Sponsor:
Collaborator:
Istituto Di Ricerche Farmacologiche Mario Negri
Information provided by (Responsible Party):
Italian Sarcoma Group

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


Condition or disease Intervention/treatment Phase
Liposarcoma Leiomyosarcoma Drug: Trabectedin Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 105 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study on Trabectedin in Advanced Retroperitoneal Leiomyosarcoma and Well Differentiated/Dedifferentiated Liposarcoma
Study Start Date : March 2014
Actual Primary Completion Date : March 12, 2019
Actual Study Completion Date : March 12, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Trabectedin

Arm Intervention/treatment
Experimental: Trabectedin

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.

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
Other Name: Yondelis




Primary Outcome Measures :
  1. Growth Modulation Rate [ Time Frame: From date of randomization until progressive disease, assessed up to 48 months ]
    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 :
  1. Objective response (OR) in the overall sample [ Time Frame: From date of randomization until progressive disease, assessed up to 48 months ]
  2. 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 ]
  3. PFS and OR in the two eligible histological types [ Time Frame: From date of randomization until progressive disease, assessed up to 48 months ]
  4. 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 ]
  5. 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 ]
  6. Efficacy of trabectedin in reducing cancer related pain [ Time Frame: From date of randomization until progressive disease, assessed up to 48 months ]
    All patients will be administered a standardized questionnaire evaluating cancer related pain and use of antalgic medication.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02247544


Locations
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Italy
Istituto Tumori Giovanni Paolo II
Bari, BA, Italy, 70124
Azienda Ospedaliera Giovanni Paolo XXIII
Bergamo, BG, Italy, 24127
Azienda Ospedaliera S. Orsola-Malpighi
Bologna, BO, Italy, 40138
A.O. Spedali Civili
Brescia, BS, Italy, 25123
Ospedale Oncologico A. Businco
Cagliari, CA, Italy, 09122
Azienda Ospedaliera S Croce e Carle
Cuneo, CN, Italy, 12100
Azienda Ospedaliera Sant'Anna
Como, CO, Italy, 22020
IRST IRCCS Meldola
Meldola, FC, Italy, 47014
Fondazione IRCCS Istituto Nazionale dei Tumori
Milano, MI, Italy, 20133
Istituto Europeo di Oncologia
Milano, MI, Italy, 20141
Istituto Clinico Humanitas
Rozzano, MI, Italy, 20089
Azienda Ospedaliera Universitaria Paolo Giaccone
Palermo, PA, Italy, 90127
Centro di Riferimento Oncologico di Aviano
Aviano, PD, Italy, 33081
Istituto Oncologico Veneto
Padova, PD, Italy, 35128
Azienda Ospedaliera Universitaria Santa Chiara
Pisa, PI, Italy, 56124
Ospedale Misericordia e Dolce
Prato, PO, Italy, 59100
Policlinico Universitario Campus Biomedico
Roma, RM, Italy, 00128
Istituto per la Ricerca e la Cura del Cancro di Candiolo
Candiolo, TO, Italy, 10060
Ospedale Gradenigo
Torino, TO, Italy, 10153
Azienda Ospedaliera Santa Maria
Terni, TR, Italy, 05100
Istituto Nazionale Tumori - IRCCS - Fondazione Pascale
Napoli, Italy, 80131
Sponsors and Collaborators
Italian Sarcoma Group
Istituto Di Ricerche Farmacologiche Mario Negri
Investigators
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Principal Investigator: Paolo G. Casali, MD IRCCS Fondazione Istituto Nazionale per la cura dei tumori di Milano

Additional Information:
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Responsible Party: Italian Sarcoma Group
ClinicalTrials.gov Identifier: NCT02247544     History of Changes
Other Study ID Numbers: ISG-STS-TRAB-2012
2012-005428-14 ( EudraCT Number )
First Posted: September 25, 2014    Key Record Dates
Last Update Posted: May 10, 2019
Last Verified: May 2019
Keywords provided by Italian Sarcoma Group:
STS, leiomyosarcoma, liposarcoma, trabectedin
Additional relevant MeSH terms:
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Leiomyosarcoma
Liposarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Neoplasms, Adipose Tissue
Trabectedin
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents