Clinical trial NCT02247544: Efficacy Study on Trabectedin in Retroperitoneal Leiomyosarcoma and Well Differentiated/Dedifferentiated Liposarcoma
Official title: A Phase II Study on Trabectedin in Advanced Retroperitoneal Leiomyosarcoma and Well Differentiated/Dedifferentiated Liposarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liposarcoma
Leiomyosarcoma
Keywords: STS, leiomyosarcoma, liposarcoma, trabectedin
Lead sponsor: Italian Sarcoma Group
Sponsor class: NETWORK
Collaborators: name: Istituto Di Ricerche Farmacologiche Mario Negri
First posted: 2014-09-25
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Growth Modulation Rate
timeFrame: From date of randomization until progressive disease, assessed up to 48 months
Secondary outcomes:
measure: Objective response (OR) in the overall sample
timeFrame: From date of randomization until progressive disease, assessed up to 48 months
measure: Pathological tumour response in the two eligible histological types, in patients undergoing surgery after treatment
timeFrame: From date of randomization until the best tumour dimensional response, assessed up to 48 months
measure: PFS and OR in the two eligible histological types
timeFrame: From date of randomization until progressive disease, assessed up to 48 months
measure: PFS in patients who undergo surgery after, or during, medical therapy and those who do not
timeFrame: From date of randomization until progressive disease, assessed up to 48 months
measure: 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
timeFrame: From date of randomization until progressive disease, assessed up to 48 months
measure: Efficacy of trabectedin in reducing cancer related pain
timeFrame: From date of randomization until progressive disease, assessed up to 48 months
Other outcomes:
Locations:
city: Bari
country: Italy
facility: Istituto Tumori Giovanni Paolo II
state: BA
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Giovanni Paolo XXIII
state: BG
city: Bologna
country: Italy
facility: Azienda Ospedaliera S. Orsola-Malpighi
state: BO
city: Brescia
country: Italy
facility: A.O. Spedali Civili
state: BS
city: Cagliari
country: Italy
facility: Ospedale Oncologico A. Businco
state: CA
city: Cuneo
country: Italy
facility: Azienda Ospedaliera S Croce e Carle
state: CN
city: Como
country: Italy
facility: Azienda Ospedaliera Sant'Anna
state: CO
city: Meldola
country: Italy
facility: IRST IRCCS Meldola
state: FC
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
state: MI
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: MI
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: MI
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Paolo Giaccone
state: PA
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico di Aviano
state: PD
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
state: PD
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Santa Chiara
state: PI
city: Prato
country: Italy
facility: Ospedale Misericordia e Dolce
state: PO
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico
state: RM
city: Candiolo
country: Italy
facility: Istituto per la Ricerca e la Cura del Cancro di Candiolo
state: TO
city: Torino
country: Italy
facility: Ospedale Gradenigo
state: TO
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria
state: TR
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori - IRCCS - Fondazione Pascale
Study officials:
affiliation: IRCCS Fondazione Istituto Nazionale per la cura dei tumori di Milano
name: Paolo G. Casali, MD
role: PRINCIPAL_INVESTIGATOR
References: