Study on Leiomyosarcoma, Liposarcomas and Synovial Sarcoma With Trabectedin

NCT ID: NCT03773510

Last Updated: 2019-05-13

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-28
• Study Completion Date: 2025-10-01

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

Detailed 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.

Conditions

Leiomyosarcoma; Liposarcoma; Synovial Sarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Trabectedin continuation

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

Group Type: ACTIVE_COMPARATOR

Trabectedin continuation

Intervention Type: DRUG

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

Trabectedin discontinuation

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.

Group Type: EXPERIMENTAL

Trabectedin discontinuation

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Trabectedin continuation

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

Intervention Type: DRUG

Other Intervention Names

Treatment discontinuation; Treatment continuation

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PharmaMar

INDUSTRY

Sponsor Role: collaborator

Italian Sarcoma Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roberta Sanfilippo, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS INT di Milano

Locations

A.O. SS Antonio e Biagio e Cesare Arrigo

Alessandria, AL, Italy

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

Meldola, FC, Italy

Istituto Europeo di Oncologia

Milan, MI, Italy

Istituto Clinico Humanitas

Rozzano, MI, Italy

Centro di Riferimento Oncologico di Aviano

Aviano, PD, Italy

Policlinico Universitario Campus Biomedico

Roma, RM, Italy

Fondazione del Piemonte per l'Oncologia IRCC Candiolo

Candiolo, Torino, Italy

Ospedale Gradenigo

Torino, TO, Italy

Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors

Bologna, , Italy

Azienda ospedaliero Universitaria Careggi di Firenze

Florence, , Italy

Fondazione IRCCS INT Milano

Milan, , Italy

Policlinico Federico II

Napoli, , Italy

Irccs Istituto Oncologico Veneto (Iov)

Padua, , Italy

Ospedale Giaccone

Palermo, , Italy

Istituti Fisioterapici Ospitalieri di Roma

Roma, , Italy

Countries

Italy

References

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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

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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.

Reference Type: BACKGROUND

PMID: 16737808 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25680558 (View on PubMed)

Other Identifiers

ISG TRADITIONS

Identifier Type: -

Identifier Source: org_study_id