TRADITIONS: Study on Leiomyosarcoma, Liposarcomas and Synovial Sarcoma With Trabectedin

Sponsor

Italian Sarcoma Group (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03773510

Collaborator

PharmaMar (Industry)

Enrollment

Locations

Arms

79.1

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Leiomyosarcoma Liposarcoma Synovial Sarcoma	Drug: Trabectedin discontinuation Drug: Trabectedin continuation	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Feb 28, 2019

Anticipated Primary Completion Date :

Oct 1, 2025

Anticipated Study Completion Date :

Oct 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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	Drug: Trabectedin continuation Patients who did not progressed after 6 cycles of trabectedin will continue the treatment until Progressive Disease or unacceptable toxicity Other Names: Treatment continuation
Experimental: 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.	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. Other Names: Treatment discontinuation

Arm

Intervention/Treatment

Active Comparator: 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

Drug: Trabectedin continuation

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

Other Names:

Treatment continuation

Experimental: 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.

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.

Other Names:

Treatment discontinuation

Outcome Measures

Primary Outcome Measures

Time secondary resistance to Trabectedin [Week 18]
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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	A.O. SS Antonio e Biagio e Cesare Arrigo	Alessandria	AL	Italy	15100
2	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST	Meldola	FC	Italy
3	Istituto Europeo di Oncologia	Milano	MI	Italy	20141
4	Istituto Clinico Humanitas	Rozzano	MI	Italy	20089
5	Centro di Riferimento Oncologico di Aviano	Aviano	PD	Italy	33081
6	Policlinico Universitario Campus Biomedico	Roma	RM	Italy	00128
7	Fondazione del Piemonte per l'Oncologia IRCC Candiolo	Candiolo	Torino	Italy	10060
8	Ospedale Gradenigo	Torino	TO	Italy	10153
9	Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors	Bologna		Italy	40136
10	Azienda ospedaliero Universitaria Careggi di Firenze	Firenze		Italy
11	Fondazione IRCCS INT Milano	Milano		Italy	20133
12	Policlinico Federico II	Napoli		Italy
13	Irccs Istituto Oncologico Veneto (Iov)	Padova		Italy
14	Ospedale Giaccone	Palermo		Italy
15	Istituti Fisioterapici Ospitalieri di Roma	Roma		Italy