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

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)

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

Study Overview

• Status: Recruiting
• Conditions: Liposarcoma, Myxoid; Liposarcoma, Dedifferentiated; Liposarcoma, Round Cell
• Intervention / Treatment: Drug: Trabectedin; Drug: Pioglitazone Oral Product

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 Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Roberta Sanfilippo, MD; Phone Number: 3495805920; Email: roberta.sanfilippo@istitutotumori.mi.it
• Study Contact Backup: Name: Valter Torri, MD; Phone Number: 0239014528; Email: valter.torri@marionegri.it

Study Locations

• Italy
  • MI
    • Milano, MI, Italy, 20133
      • Recruiting
      • Fondazione IRCCS Istituto Nazionale Tumori
      • Contact: Roberta Sanfilippo, MD; Phone Number: +39 0223902804; Email: roberta.sanfilippo@istitutotumori.mi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Pregnant or breast-feeding women
2. Partial response or progression disease as per RECIST criteria to the previous treatment with T
3. Inadequate haematological, renal and liver functions
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 (CNS) metastases
6. Active viral hepatitis or chronic liver disease
7. Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within one year before enrolment, uncontrolled arterial hypertension or arrhythmias
8. Active major infection
9. Other serious concomitant illnesses

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From the date of the enrollment up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	up to 24 months
Maximum Plasma Concentration [Cmax]	The analysis of [Cmax] will be performed on the first four enrolled patients within the safety analysis set 1.	up to 24 months

Collaborators and Investigators

• Sponsor: Mario Negri Institute for Pharmacological Research
• Collaborators: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; Humanitas Hospital, Italy
• Investigators: Study Chair: Maurizio D'Incalci, MD, Humanitas University; Study Chair: Irene De Simone, Istituto di Ricerche Farmacologiche Mario Negri IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2022
• Primary Completion (Estimated): December 2, 2024
• Study Completion (Estimated): February 2, 2025

Study Registration Dates

• First Submitted: March 3, 2021
• First Submitted That Met QC Criteria: March 10, 2021
• First Posted (Actual): March 11, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: trabectedin; pioglitazone; liposarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Adipose Tissue; Liposarcoma; Liposarcoma, Myxoid; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Pioglitazone; Trabectedin
• Other Study ID Numbers: IRFMN-SARCO-7953

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No