Neoplasms

All Conditions

Rare Diseases

Sarcoma

Liposarcoma

Leiomyosarcoma

Liposarcoma, Myxoid

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Adipose Tissue

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Trabectedin

Antineoplastic Agents, Alkylating

Alkylating Agents

Trabectedin 1.3 or 1.5mg/m2 and radiotherapy 30Gy or 45Gy.

Escalating or deescalating dose of 1.3 or 1.5mg/m2, i.v 24h, once every 3 weeks.

Cohort A: unlimited cycles. Cohort B: 3 cycles. Cohort C: 3 cycles. Cohort D: cycles of trabectedin will be provided and patients will subsequently be evaluated for surgery.

3D conformal radiotherapy (3D-CRT) or intensity modulated radiotherapy (IMRT) providing: Cohort A: 30Gy in 10 fractions (3Gy/fraction). Cohort B: 45Gy in 25 fractions (1.8Gy/fraction). Cohort C: 45Gy in 25 fractions (1.8Gy/fraction). Cohort D: 45Gy in 25 fractions (1.8Gy/fraction).

Radiotherapy

Adriana Rojo

Elisa Cerezo, MSc

Antoine Italiano, MD

Jean Yves Blay, MD

Armando Santoro, MD

Angela Buonadonna, MD

Stefano Ferrari, MD

Giovanni Grignani, MD

Alessandro Gronchi, MD

Javier Martínez-Trufero, MD

Antonio Lopez-Posa, MD

Pablo Luna, MD

Josefina Cruz, MD

Claudia Valverde, MD

Ricardo Cubedo, MD

Rosa Álvarez, MD

Andres Redondo, MD

Javier Martín-Broto, MD

Irene Carrasco, MD

Phase I-II trial that combines trabectedin plus radiotherapy for tumor reduction response measure in four cohorts of patients:

Cohort A: Patients with diagnosis of non-operable or unresectable or not oncologically recommended metastasectomy of limited to lung metastases soft tissue sarcoma.

Cohort B: Patients with locally advanced resectable Myxoid Liposarcoma. Cohort C: Patients with retroperitoneal and resectable soft tissue sarcoma (liposarcoma and leiomyosarcoma).

Cohort D (Phase II only): Patients with well differentiated liposarcoma and G2 dedifferentiated liposarcoma (with less than 30% dedifferentiated component).

Phase I: escalating dose of 1.3 or 1.5 mg/m2. Phase I for cohort C: de-escalating dose of 1.5 or 1.3mg/m2 Radiotherapy for cohort A: 30Gy in 10 fractions (3Gy/fraction). Radiotherapy for cohort B: 45Gy in 25 fractions (1.8Gy/fraction). Radiotherapy for cohort C: 45Gy in 25 fractions (1.8Gy/fraction).

Radiotherapy for cohort D: 45Gy in 25 fractions (1.8Gy/fraction). A translational substudy is developed to analyse different biomarkers predictive value.

Cohorts A and B are closed to recruitment in 2023.

In this study investigators plan to measure tumor response (RECIST and Choi criteria) when administering trabectedin standard dose or inferior with simultaneous radiotherapy treatment. The hypothesis states that administering trabectedin at 1.3mg/m2 or ≤1.5mg/m2 plus Radiotherapy 30-45Gy shows synergic activity that turns into tumor shrinkage.

A phase I trial (dose escalation -or de-escalation for cohort C- level of 1.3 or 1.5 mg/m2) will provide the proper dose level to perform a phase II trial to measure RECIST and Choi response, progression free survival, overall survival and register safety and quality of life details.

Four cohorts are indicated for this trial:

Cohort A: Patients with diagnosis of non-operable or unresectable or not oncologically recommended metastasectomy of limited to lung metastases soft tissue sarcoma.

Cohort B: Patients with locally advanced resectable Myxoid Liposarcoma, Cohort C:Patients with retroperitoneal and resectable soft tissue sarcoma (liposarcoma and leiomyosarcoma).

Cohort D: Patients with well differentiated liposarcoma and G2 dedifferentiated liposarcoma (with less than 30% dedifferentiated component) Unlimited cycles of chemotherapy are considered to be beneficial for cohort A patients, whereas cohort B and C only 3 cycles are indicated. About radiotherapy treatment, 30Gy will be given to cohort A patients, whereas cohort B and C will receive 45Gy. TCs and MRI are selected for imaging purposes.

Phase I:

For cohorts A and B:Trabectedin at two dose escalation levels:

0 1.3 mg/m2 as a 24h I.V. infusion

1 1.5 mg/m2 as a 24h I.V. infusion

For cohort C:Trabectedin at two dose de-escalation levels:

0 1.5 mg/m2 as a 24h I.V. infusion

-1 1.3 mg/m2 as a 24h I.V. infusion

Administration of trabectedin with a portable pump, i.v infusion of 24h, in cycles of 3 weeks.

Premedication:

* 4 mg oral dexamethasone 24h and 12h before chemotherapy administration.
* 20 mg I.V. dexamethasone 30minutes before treatment.
* Ondansetron or analogue will also be given prior to trabectedin.

Pathology review, radiology review and radiotherapy review are performed to each patient.

Several biomarkers are selected to perform FFPE tumor assays in relation to prediction

Trabectedin Plus Radiotherapy in Soft Tissue Sarcoma Patients

Phase I-II Prospective Trial, Multicenter, Open Label, Exploring the Combination of Trabectedin Plus Radiotherapy in Soft Tissue Sarcoma Patients

Image tumor assessment: RECIST response for the combination of trabectedin plus radiation therapy in cohorts A and B. CHOI response for the combination of trabectedin plus radiation therapy in cohort C.

In cohort D to improve 5-year relapse-free survival (RFS), decreasing the 5-year relapse percentage from 30% to 10% in patients with well differentiated liposarcoma with cellular component and dedifferentiated G2 retroperitoneal resected liposarcoma (20% increase in RFS).

CTCAE v4.03 adverse events registration to evaluate safety

Image tumor assessment measured by Choi criteria.

QLQ-C30 EORTC questionnaire to evaluate patient quality of life

Sum of complete responses, partial responses and stable diseases

percentage of relapses from diagnosis at 3 years

number of months without relapse from treatment initiation until 5 years.

percentage of protein and RNA expression of FAS, Ca2+ and NER pathways in tumor samples obtained at baseline and at surgery (approx week 11)

Centre Leon Berard

Italian Sarcoma Group

Grupo Espanol de Investigacion en Sarcomas

Myxoid Liposarcoma

Hypoglycemic Agents

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.

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

Roberta Sanfilippo, MD

Valter Torri, MD

Maurizio D'Incalci, MD

Irene De Simone

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

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

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)

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.

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.

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trabectedin Plus Radiotherapy in Soft Tissue Sarcoma Patients	NCT02275286	Liposarcoma, My... Sarcoma, Soft T... Leiomyosarcoma Liposarcoma Pleomorphic Lip...	Trabectedin Radiotherapy	18 Years -	Grupo Espanol de Investigacion en Sarcomas
Trabectedin Plus Radiotherapy in Soft Tissue Sarcoma Patients	NCT02275286	Liposarcoma, My... Sarcoma, Soft T... Leiomyosarcoma Liposarcoma Pleomorphic Lip...	Trabectedin Radiotherapy	18 Years -	Grupo Espanol de Investigacion en Sarcomas
Study on Trabectedin in Combination With Pioglitazone in Patients Myxoid Liposarcomas With Stable Disease After T Alone.	NCT04794127	Liposarcoma, My... Liposarcoma, De... Liposarcoma, Ro...	Trabectedin Pioglitazone Or...	18 Years -	Mario Negri Institute for Pharmacological Research

Spots Global Cancer Trial Database for liposarcoma, myxoid