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Study on Trabectedin in Combination With Pioglitazone in Patients Myxoid Liposarcomas With Stable Disease After T Alone. (TRABEPIO)

Primary Purpose

Liposarcoma, Myxoid, Liposarcoma, Dedifferentiated, Liposarcoma, Round Cell

Status

Unknown status

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Trabectedin

Pioglitazone Oral Product

About this trial

This is an interventional treatment trial for Liposarcoma, Myxoid focused on measuring liposarcoma, trabectedin, pioglitazone

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Diagnosis of myxoid/round cell liposarcomas
Histological diagnosis confirmation by a reference centre
Age ≥ 18 years
ECOG PS ≤2
One or more previous systemic treatments employing anthracyclines +/- ifosfamide (unless one or both are clinically contraindicated)
Four or more previous cycles of T with a stable disease as defined by RECIST criteria
Recovery from toxic effects of prior therapies to NCI CTC Grade 1 or higher
Provision of signed informed consent

Exclusion Criteria:

Pregnant or breast-feeding women
Partial response or progression disease as per RECIST criteria to the previous treatment with T
Inadequate haematological, renal and liver functions
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 (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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Trabectedin in combination with Pioglitazone

Arm Description

Trabectedin administered at a dose of 1.5 mg/m2-1.3 mg/m2 (according to investigator's choice, with a top-dose of 2.6 total mg per cycle) as a 24-hour continuous infusion via a central venous access every 3 weeks and Pioglitazone given continuously at the daily dose of 45 mg by oral route. Since Trabectedin has no cumulative toxicities, and Pioglitazone as well, the combination will be administered until progressive disease, major toxicity, patient's intolerance or unwillingness to continue treatment, or medical decision by the responsible physician.

Outcomes

Primary Outcome Measures

Objective response (OR) in patients with myxoid liposarcomas according to RECIST criteria or CHOI criteria

The primary activity endpoint is the number of responders. Patients will be considered as responders if they reach a CR or PR as best response during treatment according to RECIST criteria or according to Choi criteria.

Secondary Outcome Measures

Number and severity of Adverse Events

The safety profile of T+P is assessed by the frequency and type of treatment emergent adverse events, graded according to NCI-CTCAE v5.0, frequency and nature of SAEs.

Maximum Plasma Concentration [Cmax]

The analysis of [Cmax] will be performed on the first four enrolled patients within the safety analysis set 1.

Full Information

NCT ID

NCT04794127

First Posted

March 3, 2021

Last Updated

March 10, 2021

Sponsor

Mario Negri Institute for Pharmacological Research

Collaborators

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Humanitas Hospital, Italy

1. Study Identification

Unique Protocol Identification Number

NCT04794127

Brief Title

Study on Trabectedin in Combination With Pioglitazone in Patients Myxoid Liposarcomas With Stable Disease After T Alone.

Acronym

TRABEPIO

Official Title

A Phase II Study on Trabectedin in Combination With PPARg Agonist Pioglitazone in Patients With Round Cell Myxoid Liposarcomas or Dedifferentiated G1 and G2 Liposarcomas With Stable Disease After a Monotherapy With Trabectedin. (TRABEPIO)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Unknown status

Study Start Date

April 24, 2021 (Anticipated)

Primary Completion Date

April 24, 2022 (Anticipated)

Study Completion Date

April 24, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mario Negri Institute for Pharmacological Research

Collaborators

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Humanitas Hospital, Italy

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a phase 2 study conducted in two sequential stages: The first stage is an Italian single institution, single arm, pilot study, aimed at exploring the activity of the combination T and P in myxoid liposarcoma patients who achieved a stable disease after a minimum of 4 cycles of T alone. If a minimum required activity will be demonstrated from the first stage, the second stage of the study will be conducted;otherwise, the study will be stopped. The second stage is an Italian open-label, multicenter, randomized, double arm, phase II trial, aimed at evaluating the combination of T and P in myxoid liposarcoma and G1 or G2 dedifferentiated liposarcomas compared to the standard treatment with T alone. Patients will be randomized with a 1:1 ratio to treatments arms as specified below: Control arm (A): T alone Experimental arm (B): T in combination with P

Detailed Description

In the specific the first stage will be an Italian mono-institutional, single arm, pilot study exploring the activity of the combination of T and P in myxoid liposarcoma patients who achieved a stable disease after a minimum of 4 cycles of T alone. If a minimum required activity will be demonstrated from the first stage, the second stage of the study will be conducted; otherwise, the study will be stopped. The second stage will be an Italian multicenter, open-label, randomized, double arm, phase II trial, aimed at evaluating the combination of T and P in myxoid liposarcoma and G1 or G2 dedifferentiated liposarcomas compared to the standard treatment. Patients will be randomized by a centralized computer system with a 1:1 ratio to one of the following two arms: Control arm (A): T alone Experimental arm (B): T in combination with P The pilot study will be conducted in Italy at Istituto Nazionale Tumori Milano in order to recruit 10 evaluable patients. The second stage will be conducted in approximately 10 italian centers in order to recruit 80 evaluable patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liposarcoma, Myxoid, Liposarcoma, Dedifferentiated, Liposarcoma, Round Cell

Keywords

liposarcoma, trabectedin, pioglitazone

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Phase II, pilot, open-label study

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Trabectedin in combination with Pioglitazone

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Trabectedin

Other Intervention Name(s)

Trabectedine

Intervention Description

Patients will be treated with Trabectedin administered at a dose of 1.5 mg/m2-1.3 mg/m2 (according to investigator's choice, with a top-dose of 2.6 total mg per cycle) as a 24-hour continuous infusion via a central venous access every 3 weeks and pioglitazone given continuously at the daily dose of 45 mg by oral route.

Intervention Type

Drug

Intervention Name(s)

Pioglitazone Oral Product

Other Intervention Name(s)

Pioglitazone

Intervention Description

Primary Outcome Measure Information:

Title

Objective response (OR) in patients with myxoid liposarcomas according to RECIST criteria or CHOI criteria

Description

Time Frame

From the date of the enrollment up to 24 months

Secondary Outcome Measure Information:

Title

Number and severity of Adverse Events

Description

The safety profile of T+P is assessed by the frequency and type of treatment emergent adverse events, graded according to NCI-CTCAE v5.0, frequency and nature of SAEs.

Time Frame

up to 24 months

Title

Maximum Plasma Concentration [Cmax]

Description

The analysis of [Cmax] will be performed on the first four enrolled patients within the safety analysis set 1.

Time Frame

up to 24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Diagnosis of myxoid/round cell liposarcomas Histological diagnosis confirmation by a reference centre Age ≥ 18 years ECOG PS ≤2 One or more previous systemic treatments employing anthracyclines +/- ifosfamide (unless one or both are clinically contraindicated) Four or more previous cycles of T with a stable disease as defined by RECIST criteria Recovery from toxic effects of prior therapies to NCI CTC Grade 1 or higher Provision of signed informed consent Exclusion Criteria: Pregnant or breast-feeding women Partial response or progression disease as per RECIST criteria to the previous treatment with T Inadequate haematological, renal and liver functions 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 (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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Roberta Sanfilippo, MD

Phone

3495805920

roberta.sanfilippo@istitutotumori.mi.it

First Name & Middle Initial & Last Name or Official Title & Degree

Valter Torri, MD

Phone

0239014528

valter.torri@marionegri.it

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Maurizio D'Incalci, MD

Organizational Affiliation

Humanitas University

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Irene De Simone

Organizational Affiliation

Istituto di Ricerche Farmacologiche Mario Negri IRCCS

Official's Role

Study Chair

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Study on Trabectedin in Combination With Pioglitazone in Patients Myxoid Liposarcomas With Stable Disease After T Alone.

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