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

NCT ID: NCT04794127

Last Updated: 2024-03-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-02
• Study Completion Date: 2025-02-02

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Trabectedin

Intervention Type: DRUG

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.

Pioglitazone Oral Product

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Trabectedine; Pioglitazone

Eligibility Criteria

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

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

Sponsors

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

OTHER

Sponsor Role: collaborator

Humanitas Hospital, Italy

OTHER

Sponsor Role: collaborator

Mario Negri Institute for Pharmacological Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maurizio D'Incalci, MD

Role: STUDY_CHAIR

Humanitas University

Irene De Simone

Role: STUDY_CHAIR

Istituto Di Ricerche Farmacologiche Mario Negri

Locations

Fondazione IRCCS Istituto Nazionale Tumori

Milan, MI, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Roberta Sanfilippo, MD

Role: CONTACT

roberta.sanfilippo@istitutotumori.mi.it

3495805920

Valter Torri, MD

Role: CONTACT

valter.torri@marionegri.it

0239014528

Facility Contacts

Roberta Sanfilippo, MD

Role: primary

roberta.sanfilippo@istitutotumori.mi.it

0223902804 ext. +39

Other Identifiers

IRFMN-SARCO-7953

Identifier Type: -

Identifier Source: org_study_id