Study on Leiomyosarcoma, Liposarcomas and Synovial Sarcoma With Trabectedin

Leiomyosarcoma Clinical Trial

— TRADITIONS  

Official title:

Time to Secondary Resistance to Trabectedin After Interruption Versus Continuation in Responding Patients With Liposarcoma, Leiomyosarcoma and Synovial Sarcoma

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03773510
• Other study ID #: ISG TRADITIONS
• Status: Withdrawn
• Phase: Phase 3
• Start date: February 28, 2019
• Est. completion date: October 1, 2025

Study information

• Verified date: May 2019
• Source: Italian Sarcoma Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

This is an Italian, multicenter, randomized, open-label , two arm, 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. The aim is to evaluate the best clinical practice for responding patients as Trabectedin has an acceptable safety profile with no evidence of cumulative toxicity.

After signing informed consent and being assessed for eligibility criteria , eligible patients will start the trabectedin treatment.

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.

The study will be conducted in Italy in approximately 12 centers, in order to recruit 330 evaluable patients over a 4 year period. The follow-up will last approximately 3 years.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 1, 2025
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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

2. Diagnosis of well differentiated/dedifferentiated liposarcoma, mixoid round cell liposarcoma, leiomyosarcoma or synovial sarcoma

3. Persistent or locally relapsed and/or metastatic disease

4. 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).

5. Age = 18 years

6. Adequate bone marrow function

7. Adequate organ function,

8. Eastern Cooperative Oncology Group Performance Status = 2

9. One or more previous systemic treatments with anthracyclines with or without ifosfamide (unless one or both are clinically contraindicated)

10. 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

11. A minimum of 3 weeks since any previous chemotherapy treatment

12. Recovery from toxic effects of prior therapies to (Grade 1 or lower)

13. 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.

Exclusion Criteria:

1. Pregnant or breast-feeding women

2. Prior exposure to Trabectedin

3. Peripheral neuropathy, Grade 2 or higher

4. 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

5. Known central nervous system metastases

6. Active viral hepatitis or chronic liver disease

7. Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within six months before enrollment, uncontrolled arterial hypertension or arrhythmia

8. Active major infection

9. Previous treatment with any other investigational or not investigational agents within 14 days of first day of study drug dosing

10. Known history of human immunodeficiency virus infection

11. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs

12. Other serious concomitant illnesses or any condition that may interfere with the subject's participation in the study or evaluation of the study results

Related Conditions & MeSH terms

• Leiomyosarcoma
• Liposarcoma
• Sarcoma
• Sarcoma, Synovial
• Synovial Sarcoma

Intervention

Drug:
• Trabectedin discontinuation
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.
• Trabectedin continuation
Patients who did not progressed after 6 cycles of trabectedin will continue the treatment until Progressive Disease or unacceptable toxicity

Locations

Country	Name	City	State
Italy	A.O. SS Antonio e Biagio e Cesare Arrigo	Alessandria	AL
Italy	Centro di Riferimento Oncologico di Aviano	Aviano	PD
Italy	Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors	Bologna
Italy	Fondazione del Piemonte per l'Oncologia IRCC Candiolo	Candiolo	Torino
Italy	Azienda ospedaliero Universitaria Careggi di Firenze	Firenze
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST	Meldola	FC
Italy	Fondazione IRCCS INT Milano	Milano
Italy	Istituto Europeo di Oncologia	Milano	MI
Italy	Policlinico Federico II	Napoli
Italy	Irccs Istituto Oncologico Veneto (Iov)	Padova
Italy	Ospedale Giaccone	Palermo
Italy	Istituti Fisioterapici Ospitalieri di Roma	Roma
Italy	Policlinico Universitario Campus Biomedico	Roma	RM
Italy	Istituto Clinico Humanitas	Rozzano	MI
Italy	Ospedale Gradenigo	Torino	TO

Sponsors (2)

Lead Sponsor	Collaborator
Italian Sarcoma Group	PharmaMar

Country where clinical trial is conducted

Italy, 

References & 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. Review. — View Citation

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. — View Citation

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. Epub 2006 Jun 5. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival	Overall Survival is the time from the first trabectedin dose to death for any cause	month 6,month 12, month 18, month 24, months 30, month 36, month 42, month 48, month 54, month 60
Secondary	Incidence of adverse event	Adverse events are evaluate from the first trabectedin dose throughout the study according to CTCAE 5.0	Week 9, week 18, week 27, week 36, week 45, week 54, week 63, week 72, week 81
Secondary	Progression free survival	Time from the first trabectedin dose to time of onset of progression disease	Week 9, week 18, week 27, week 36, week 45, week 54, week 63, week 72, week 81