Study on Leiomyosarcoma, Liposarcomas and Synovial Sarcoma With Trabectedin

NCT03773510 | Withdrawn Phase 3

• 1 other identifier: ISG TRADITIONS
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 15

Brief Summary

Two arm, randomized, open-label study, to determine the best time to secondary resistance between responding patients who discontinue treatment and resumed Trabectedin at the time of progression versus patients who continued treatment until progression. T

Conditions

Leiomyosarcoma; Liposarcoma; Synovial Sarcoma

Keywords

trabectedin; soft tissue sarcoma

Outcome Measures

Primary Outcomes (1)

• Time secondary resistance to Trabectedin

  Time secondary resistance to Trabectedin is the time from the first trabectedin dose to progression not amenable to treatment with Trabectedin, or death, whichever occurs first

  Week 18

Secondary Outcomes (3)

• Overall Survival

  month 6,month 12, month 18, month 24, months 30, month 36, month 42, month 48, month 54, month 60

• Incidence of adverse event

  Week 9, week 18, week 27, week 36, week 45, week 54, week 63, week 72, week 81

• Progression free survival

  Week 9, week 18, week 27, week 36, week 45, week 54, week 63, week 72, week 81

Study Arms (2)

Trabectedin continuation

ACTIVE COMPARATOR

All the patients who will complete 6 cycles of trabectedin without disease progression, will continue trabectedin until progressive disease, unacceptable toxicity, patient or investigator decision

Drug: Trabectedin continuation

Trabectedin discontinuation

EXPERIMENTAL

All the patients who will complete 6 cycles of trabectedin without disease progression , will discontinue trabectedin. The treatment will be resumed again at progression for other 6 cycles and this scheme of treatment will be proposed until progression under trabectedin.

Drug: Trabectedin discontinuation

Interventions

Trabectedin discontinuation DRUG

Patients who did not progressed after 6 cycles of trabectedin will stop the treatment and resume drug in case of progression for other 6 cycles. The treatment will be resumed again at progression for other 6 cycles and this scheme of treatment will be proposed until progression under trabectedin.

Also known as: Treatment discontinuation

Trabectedin discontinuation

Trabectedin continuation DRUG

Patients who did not progressed after 6 cycles of trabectedin will continue the treatment until Progressive Disease or unacceptable toxicity

Also known as: Treatment continuation

Trabectedin continuation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient or legal representative must be able to read and understand the informed consent form and must have been willing to give written informed consent and any locally required authorization before any study-specific procedures, including screening evaluations, sampling, and analyses
• Diagnosis of well differentiated/dedifferentiated liposarcoma, mixoid round cell liposarcoma, leiomyosarcoma or synovial sarcoma
• Persistent or locally relapsed and/or metastatic disease
• Pathology specimens available for centralized review (central review is not mandatory prior to start the treatment, but within a month from screening, tumor sample must be sent to central pathology reviewer for a retrospective diagnosis confirmation).
• Age ≥ 18 years
• Adequate bone marrow function
• Adequate organ function,
• Eastern Cooperative Oncology Group Performance Status ≤ 2
• One or more previous systemic treatments with anthracyclines with or without ifosfamide (unless one or both are clinically contraindicated)
• Measurable disease. Patient who received radiotherapy within 3 weeks form the treatment start, can be included as long there is a measurable lesion outside of the irradiation field
• A minimum of 3 weeks since any previous chemotherapy treatment
• Recovery from toxic effects of prior therapies to (Grade 1 or lower)
• Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation each cycle of chemotherapy. Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective method of birth control throughout the study.

You may not qualify if:

• Pregnant or breast-feeding women
• Prior exposure to Trabectedin
• Peripheral neuropathy, Grade 2 or higher
• History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission from 5 years or more and judged of negligible potential of relapse
• Known central nervous system metastases
• Active viral hepatitis or chronic liver disease
• Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within six months before enrollment, uncontrolled arterial hypertension or arrhythmia
• Active major infection
• Previous treatment with any other investigational or not investigational agents within 14 days of first day of study drug dosing
• Known history of human immunodeficiency virus infection
• Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
• Other serious concomitant illnesses or any condition that may interfere with the subject's participation in the study or evaluation of the study results

Sponsors & Collaborators

• Italian Sarcoma Group: lead
• PharmaMar: collaborator

Study Sites (15)

A.O. SS Antonio e Biagio e Cesare Arrigo

Alessandria, AL, 15100, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST

Meldola, FC, Italy

Location

Istituto Europeo di Oncologia

Milan, MI, 20141, Italy

Location

Istituto Clinico Humanitas

Rozzano, MI, 20089, Italy

Location

Centro di Riferimento Oncologico di Aviano

Aviano, PD, 33081, Italy

Location

Policlinico Universitario Campus Biomedico

Roma, RM, 00128, Italy

Location

Fondazione del Piemonte per l'Oncologia IRCC Candiolo

Candiolo, Torino, 10060, Italy

Location

Ospedale Gradenigo

Torino, TO, 10153, Italy

Location

Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors

Bologna, 40136, Italy

Location

Azienda ospedaliero Universitaria Careggi di Firenze

Florence, Italy

Location

Fondazione IRCCS INT Milano

Milan, 20133, Italy

Location

Policlinico Federico II

Napoli, Italy

Location

Irccs Istituto Oncologico Veneto (Iov)

Padua, Italy

Location

Ospedale Giaccone

Palermo, Italy

Location

Istituti Fisioterapici Ospitalieri di Roma

Roma, Italy

Location

Related Publications (5)

• D'Incalci M, Galmarini CM. A review of trabectedin (ET-743): a unique mechanism of action. Mol Cancer Ther. 2010 Aug;9(8):2157-63. doi: 10.1158/1535-7163.MCT-10-0263. Epub 2010 Jul 20.

  PMID: 20647340 BACKGROUND

• Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, Van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial. J Clin Oncol. 2016 Mar 10;34(8):786-93. doi: 10.1200/JCO.2015.62.4734. Epub 2015 Sep 14.

  PMID: 26371143 BACKGROUND

• Sanfilippo R, Dileo P, Blay JY, Constantinidou A, Le Cesne A, Benson C, Vizzini L, Contu M, Baldi GG, Dei Tos AP, Casali PG. Trabectedin in advanced synovial sarcomas: a multicenter retrospective study from four European institutions and the Italian Rare Cancer Network. Anticancer Drugs. 2015 Jul;26(6):678-81. doi: 10.1097/CAD.0000000000000228.

  PMID: 25763543 BACKGROUND

• Grosso F, Dileo P, Sanfilippo R, Stacchiotti S, Bertulli R, Piovesan C, Jimeno J, D'Incalci M, Gescher A, Casali PG. Steroid premedication markedly reduces liver and bone marrow toxicity of trabectedin in advanced sarcoma. Eur J Cancer. 2006 Jul;42(10):1484-90. doi: 10.1016/j.ejca.2006.02.010. Epub 2006 Jun 5.

  PMID: 16737808 BACKGROUND

• Le Cesne A, Blay JY, Domont J, Tresch-Bruneel E, Chevreau C, Bertucci F, Delcambre C, Saada-Bouzid E, Piperno-Neumann S, Bay JO, Mir O, Ray-Coquard I, Ryckewaert T, Valentin T, Isambert N, Italiano A, Clisant S, Penel N. Interruption versus continuation of trabectedin in patients with soft-tissue sarcoma (T-DIS): a randomised phase 2 trial. Lancet Oncol. 2015 Mar;16(3):312-9. doi: 10.1016/S1470-2045(15)70031-8. Epub 2015 Feb 11.

  PMID: 25680558 BACKGROUND

MeSH Terms

Conditions

Leiomyosarcoma; Liposarcoma; Sarcoma, Synovial; Sarcoma

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Adipose Tissue; Neoplasms, Connective Tissue

Study Officials

• Roberta Sanfilippo, MD

  Fondazione IRCCS INT di Milano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Randomized, open-label , two arm study All the patients who will complete 6 cycles of treatment without disease progression will be be randomized to continue Trabectedin versus "treatment interruption" followed by re-challenge at progression. Patients randomized to discontinue treatment will be candidate to other 6 cycles of treatment and if they do not progress, to another interruption. The treatment will be resumed again at progression for other 6 cycles and this scheme of treatment will be proposed until progression under Trabectedin.

Study Record Dates

• First Submitted: December 10, 2018
• First Posted: December 12, 2018
• Study Start: February 28, 2019
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: May 13, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (15)