Clinical trial NCT04794127: Study on Trabectedin in Combination With Pioglitazone in Patients Myxoid Liposarcomas With Stable Disease After T Alone.
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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Liposarcoma, Myxoid
Liposarcoma, Dedifferentiated
Liposarcoma, Round Cell
Keywords: liposarcoma
trabectedin
pioglitazone
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
Collaborators: name: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
name: Humanitas Hospital, Italy
First posted: 2021-03-11
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase II, pilot, open-label study
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective response (OR) in patients with myxoid liposarcomas according to RECIST criteria or CHOI criteria
timeFrame: From the date of the enrollment up to 24 months
Secondary outcomes:
measure: Number and severity of Adverse Events
timeFrame: up to 24 months
measure: Maximum Plasma Concentration [Cmax]
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale Tumori
state: MI
Study officials:
affiliation: Humanitas University
name: Maurizio D'Incalci, MD
role: STUDY_CHAIR
affiliation: Istituto Di Ricerche Farmacologiche Mario Negri
name: Irene De Simone
role: STUDY_CHAIR
References: