Cohort A:Soft Tissue Sarcoma with metastasis limited to lung, and not suitable for metastasectomy or surgery resection or not oncologically recommended metastasectomy. Cohort B : Myxoid Liposarcoma, deep located and more than 5 cm or superficial more than 10 cm. Tumor must be resectable and without evidence of regional or distal spread after adequate staging procedure. Tumor must be located in limbs or superficial trunk wall. MedDRA version: 20.0 Level: HLT Classification code 10041298 Term: S
Conditions
Sponsors
GRUPO ESPAñOL DE INVESTIGACIóN EN SARCOMAS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cohort A 1. The patient must sign voluntarily the informed consent 2. Age = 18 years old 3. Patients must have a diagnostic of Soft Tissue Sarcoma with metastasis and not suitable for metastasectomy or surgery resection 4. Documentation of disease progression within 6 months prior to study entry. 5. The patient must have been considered eligible for systemic chemotherapy. A maximum of two previous lines for advanced/metastatic disease are allowed as long as trabectedin has not been included. 6. The following histological subtypes can be included: - Undifferentiated pleomorphic sarcoma (previously, malignant fibrous histiocytoma) - Leiomyosarcoma - Angiosarcoma/ epithelial hemangioendothelioma - Liposarcoma and its variants - Synovial sarcoma - Fibrosarcoma and its variants - Hemangiopericytoma/solitary fibroid tumor - Neurogenic sarcoma (Malignant peripheral nerve sheath tumor, MPNST) - Myxofibrosarcoma - Epithelioid Sarcoma - Unclassified sarcoma (spindle cell/epithelioid/pleomorphic/myxoid) 7. Measurable disease, according to RECIST V 1.1 criteria 8. Performance status =1 9. Adequate respiratory functions: FEV1 >1L, DLCO>40% (patients with pulmonary target lesions) 10. Adequate bone marrow, hepatic and renal function. 11. Men or women of childbearing potential should be using an effective method of contraception before entry into the study and throughout the same and for 6 months after ending the study. 12. Normal cardiac function with a LVEF = 50% Cohort B 1. The patient must sign voluntarily the informed consent 2. Age = 18 years old 3. Pathological diagnosis of Myxoid Liposarcoma, deep located and more than 5 cm or superficial more than 10 cm. 4. Tumor must be resectable and without evidence of regional or distal spread after adequate staging procedure. Tumor must be located in limbs or superficial trunk wall. 5. Measurable disease, according to RECIST 1.1 6. Performance status 0-1 (ECOG). 7. Adequate bone marrow, renal and hepatic function 8. Men or women of child bearing potential should be using an effective method of contraception before entry into the study and throughout the same and for 6 months after ending the study. 9. Normal cardiac function with a LVEF = 50% Cohort C 1. The patient must sign voluntarily the informed consent 2. Age = 18 years old 3. The following histological subtypes may be included: High grade leiomyosarcoma (G2-3), liposarcoma, if at least 30% of the tumour is dedifferentiated, pleomorphic liposarcoma. 4. The tumour must be located in the retroperitoneum and it must be resectable 5. Measurable disease, according to RECIST 1.1 6. ECOG performance status 0–1. 7. Adequate bone marrow, renal and hepatic function 8. Fertile men or women must use an effective contraceptive method before starting the study, during the study and for 6 months following the conclusion thereof. 9. Normal cardiac function with LVEF =50% by echocardiogram or MUGA. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 111 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
Exclusion criteria: COHORT A 1. Previous treatment with trabectedin or RT 2. Performance status = 2 3. Plasma bilirubin > UNL. 4. Creatinine > 1.6 mg/dL. 5. History of other neoplastic disease with less than 5 years free of disease with the exception of basal cell carcinoma or in situ cervical cancer adequately treated. 6. Severe COPD or other severe pulmonary diseases. 7. Significant cardiovascular disease 8. Significant systemic diseases grade 3 or higher -CTCAE v4.03 scale. 9. Uncontrolled infections. 10. Known positive test for infection by human immunodeficiency virus (HIV). 11. Women who are pregnant or breast-feeding. Cohort B 1. Unresectable tumors (with limb sparing surgery) 2. More than 1 previous chemotherapy treatment for local disease including trabectedin. 3. RT involving the tumoral bed. 4. Performance status = 2 5. Presence of metastases or lymph node involvement by the tumor. 6. Location other than limb or superficial trunk wall. 7. Plasma bilirubin > UNL. 8. Creatinine > 1.6 mg/dL. 9. History of other neoplastic disease with less than 5 years free of disease with the exception of basal cell carcinoma or in situ cervical cancer adequately treated. 10. Significant cardiovascular disease 11. Significant systemic diseases grade 3 or higher on the NCI-CTCAE v4.03 scale, that limit patient availability, or according to investigator judgment may contribute significantly to treatment toxicity. 12. Uncontrolled bacterial, mycotic or viral infections. 13. Known positive test for infection by human immunodeficiency virus (HIV). 14. Women who are pregnant or breast-feeding. Cohort C 1. Unresectable tumours. 2. Location other than the retroperitoneum. 3. Patients who have previously received systemic treatment (chemotherapy or trabectedin). 4. Patients who underwent prior local treatment for retroperitoneal sarcoma: surgery or radiotherapy in the tumour bed. 5. ECOG performance status =2. 6. Presence of metastasis or lymph node involvement of the tumour. 7. Previous history of another neoplastic disease with less than 5 years free of disease, except for basal cell carcinoma or properly treated in situ cervical cancer. 8. Significant cardiovascular disease 9. A significant grade 3 or greater systemic disease on the NCI-CTCAE v4.03 scale, 10. Uncontrolled viral, mycotic or bacterial infections. 11. Known HIV-positive patients. 12. Pregnant or breast-feeding women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: oTo describe safety profile for each cohort and dose level of trabectedin in order to find the recommended dose for phase II part in a specific way for each cohort of treatment. That is, the maximum tolerable dosage according the protocol. Toxicity will be evaluated on the basis of on adverse events (CTCAE v4.03) for both cohorts. ;Secondary Objective: oRECIST response for the combination of trabectedin plus radiation therapy in both cohorts. oFor cohort A: Efficacy response measured by progression free survival (PFS), overall survival (OS), ORRand potential predictive/prognostic biomarkers. oFor cohort B: Efficacy measured by recurrence free survival (RFS). oFor cohort B: Activity measured by functional imaging, pathologic response and potential predictive/prognostic biomarkers oChoi criteria response (for both cohorts) oQuality of Life measured by QLQ-C30 EORTC questionnaire (for both cohorts);Primary end point(s): All cohorts: response according RECIST 1.1;Timepoint(s) of evaluation of this end point: For phase I and II of cohort A, the imaging evaluation will be performed at baseline and every 6 weeks until disease progression. For phase I and II of cohort B, the imaging evaluation to assess response following RECIST criteria, will be performed at baseline, from starting treatment and at follow up: MRI every 4 months in 1st year, every 6 months during 2nd and 3rd year; Thorax/Abdo CT scan will be performed every 4 months during 3 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Cohort A: - Assessment of adverse events following CTCAE v4.03 - Progression Free survival, Overall Survival, potential predictive/prognostic biomarkers. - CHOI criteria response - QLQ-C30 EORTC questionnaire Cohort B: -Assessment of adverse events following CTCAE v4.03 - Activity assessed by Functional imaging, pathologic response and potential predictive/prognostic biomarkers. -Recurrence free survival -CHOI criteria Response -QLQ-C30 EORTC questionnaire;Timepoint(s) of evaluation of this end point: Adverse events will be evaluated at the beginning of each cycle prior to treatment, and end of treatment -For phase I and II of cohort A, the imaging evaluation will be performed at baseline and every 6 weeks until disease progression. For phase I and II of cohort B, the imaging evaluation to assess response following RECIST criteria, will be performed at baseline, week 10 from starting treatment and at follow up: MRI every 4 months in 1st year, every 6 months during 2nd and 3rd year; Thorax/Abdo CT scan will be performed every 4 months during 3 years. - tumor collection and blood extractions. -Questionnaires in cohort A will be done at baseline, and every 3 cycles until end of treatment; cohort B at baseline, week 10 from beginning of treatment and at end of treatment | — |
Countries
France, Italy, Spain
Contacts
Public ContactClininal Research Center
GEIS
Outcome results
None listed