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

Sponsor

Mario Negri Institute for Pharmacological Research (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04794127

Collaborator

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano (Other), Humanitas Hospital, Italy (Other)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Liposarcoma, Myxoid Liposarcoma, Dedifferentiated Liposarcoma, Round Cell	Drug: Trabectedin Drug: Pioglitazone Oral Product	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Phase II, pilot, open-label studyPhase II, pilot, open-label study

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Apr 24, 2021

Anticipated Primary Completion Date :

Apr 24, 2022

Anticipated Study Completion Date :

Apr 24, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Trabectedin in combination with Pioglitazone 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.	Drug: Trabectedin 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. Other Names: Trabectedine Drug: Pioglitazone Oral Product 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. Other Names: Pioglitazone

Arm

Intervention/Treatment

Experimental: Trabectedin in combination with Pioglitazone

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.

Drug: Trabectedin

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.

Other Names:

Trabectedine

Drug: Pioglitazone Oral Product

Other Names:

Pioglitazone

Outcome Measures

Primary Outcome Measures

Objective response (OR) in patients with myxoid liposarcomas according to RECIST criteria or CHOI criteria [From the date of the enrollment up to 24 months]
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 [up to 24 months]
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] [up to 24 months]
The analysis of [Cmax] will be performed on the first four enrolled patients within the safety analysis set 1.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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