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

Sponsor

Italian Sarcoma Group (Other)

Overall Status

Completed

CT.gov ID

NCT02247544

Collaborator

Istituto Di Ricerche Farmacologiche Mario Negri (Other)

105

Enrollment

Locations

Arm

60.4

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

105 participants

Allocation:

N/A

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 :

Mar 1, 2014

Actual Primary Completion Date :

Mar 12, 2019

Actual Study Completion Date :

Mar 12, 2019

Arms and Interventions

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 Names: Yondelis

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 Names:

Yondelis

Outcome Measures

Primary Outcome Measures

Growth Modulation Rate [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

Objective response (OR) in the overall sample [From date of randomization until progressive disease, assessed up to 48 months]
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]
PFS and OR in the two eligible histological types [From date of randomization until progressive disease, assessed up to 48 months]
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]
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]
Efficacy of trabectedin in reducing cancer related pain [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Istituto Tumori Giovanni Paolo II	Bari	BA	Italy	70124
2	Azienda Ospedaliera Giovanni Paolo XXIII	Bergamo	BG	Italy	24127
3	Azienda Ospedaliera S. Orsola-Malpighi	Bologna	BO	Italy	40138
4	A.O. Spedali Civili	Brescia	BS	Italy	25123
5	Ospedale Oncologico A. Businco	Cagliari	CA	Italy	09122
6	Azienda Ospedaliera S Croce e Carle	Cuneo	CN	Italy	12100
7	Azienda Ospedaliera Sant'Anna	Como	CO	Italy	22020
8	IRST IRCCS Meldola	Meldola	FC	Italy	47014
9	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	MI	Italy	20133
10	Istituto Europeo di Oncologia	Milano	MI	Italy	20141
11	Istituto Clinico Humanitas	Rozzano	MI	Italy	20089
12	Azienda Ospedaliera Universitaria Paolo Giaccone	Palermo	PA	Italy	90127
13	Centro di Riferimento Oncologico di Aviano	Aviano	PD	Italy	33081
14	Istituto Oncologico Veneto	Padova	PD	Italy	35128
15	Azienda Ospedaliera Universitaria Santa Chiara	Pisa	PI	Italy	56124
16	Ospedale Misericordia e Dolce	Prato	PO	Italy	59100
17	Policlinico Universitario Campus Biomedico	Roma	RM	Italy	00128
18	Istituto per la Ricerca e la Cura del Cancro di Candiolo	Candiolo	TO	Italy	10060
19	Ospedale Gradenigo	Torino	TO	Italy	10153
20	Azienda Ospedaliera Santa Maria	Terni	TR	Italy	05100
21	Istituto Nazionale Tumori - IRCCS - Fondazione Pascale	Napoli		Italy	80131