NCT02275286

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 199 (estimated)
• Sponsor: Grupo Espanol de Investigacion en Sarcomas · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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

Conditions

• Liposarcoma, Myxoid
• Sarcoma, Soft Tissue
• Leiomyosarcoma
• Liposarcoma
• Pleomorphic Liposarcoma

Interventions

Type	Name	Description
DRUG	Trabectedin	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.
RADIATION	Radiotherapy	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).

Timeline

• Start date: 2014-11-01
• Primary completion: 2028-06-01
• Completion: 2028-06-01
• First posted: 2014-10-27
• Last updated: 2023-05-31

Locations

17 sites across 3 countries: France, Italy, Spain