Trabectedin Plus Radiotherapy in Soft Tissue Sarcoma Patients

Recruiting now · Phase 1/Phase 2

Conditions studied: Liposarcoma, Myxoid, Sarcoma, Soft Tissue, Leiomyosarcoma, Liposarcoma, Pleomorphic Liposarcoma

In brief

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.

Key facts

Study ID

NCT02275286

Run by

Grupo Espanol de Investigacion en Sarcomas

People needed

199

Starts

2014-11-01

Expected to finish

2028-06-01

Last updated by the study team

2023-05-31

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• The patient must sign voluntarily the informed consent form before any study test is conducted that is not part of routine patient care.
• Aged equal or over 18.
• Patients must have a diagnostic of Soft Tissue Sarcoma with metastasis limited to lung, and not suitable for metastasectomy or surgery resection or not oncologically recommended metastasectomy.A centralized diagnostic will be performed, the tumor sample must be available and sent prior to inclusion.
• Disease distribution allows meeting with normal tissue constraints of radiation therapy. Radiation oncologist must confirm this point.
• Metastatic spread could be present in two organs at maximum (i.e. lungs and pelvic fosa).
• Those lesions considered for radiation therapy have to be considered as target lesions as well. (i.e. in a patient with nodules in lungs, those lesions selected for radiation therapy have to include at least the target lesions)
• It is allowed that not all the lesions will be under radiation fields. As a general rule, it will be prioritized to select, as target-irradiating lesions, those with greater increase in size and those largest lesions. It should be discouraged to irradiate pulmonary lesions with infiltration of pleural serosa.
• Patients must have documentation of disease progression within 6 months prior to study entry.
• 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.
• The following histological subtypes can be included:
• Undifferentiated pleomorphic sarcoma (previously, malignant fibrous histiocytoma) Leiomyosarcoma Angiosarcoma/ epithelial hemangioendothelioma Liposarcoma and its variants (well differentiated, dedifferentiated, myxoid/round cells, pleomorphic).
• Synovial sarcoma Fibrosarcoma and its variants (epithelial fibrosarcoma/low grade fibromyxoid sarcoma) Hemangiopericytoma/solitary fibroid tumor Neurogenic sarcoma (Malignant peripheral nerve sheath tumor, MPNST) Myxofibrosarcoma Epithelioid Sarcoma Unclassified sarcoma (spindle cell/epithelioid/pleomorphic/myxoid)
• Measurable disease, according to RECIST V 1.1 criteria
• Performance status ≤1 (ECOG).
• Adequate respiratory functions: FEV1 >1L; DLco > 40% (patients with pulmonary target lesions)
• Adequate bone marrow function (hemoglobin > 10 g/dl, leukocytes ≥ 3.000/mm3, neutrophils ≥ 1.500/mm3, platelets ≥ 100.000/mm3). Patients with plasma creatinine ≤ 1,6 mg/dl, transaminases ≤ 2.5 times the UNL, total bilirubin ≤ UNL, CPK ≤ 2.5 times UNL, alkaline phosphatase ≤ 2.5 times the UNL are acceptable. If the increase of alkaline phosphatase is > 2.5 times the UNL, then the alkaline phosphatase liver fraction and/or GGT must be ≤ UNL.
• 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. Women of childbearing potential must have a negative urine pregnancy test before study entry.
• Normal cardiac function with a LVEF ≥ 50% by echocardiogram or MUGA.
• It should be performed HBV and HCV serologies prior to inclusion. If HbsAg is positive it is recommended to reject the existence of replicative phase (HbaAg+, DNA VHB+). If these were positives the inclusion is not recommended, remaining at investigators' discretion the preventive treatment with lamivudine. If a potential patient is positive for anti-HCV antibodies, presence of the virus should be ruled out with a qualitative PCR, or the patient should NOT be included in the study (if a qualitative PCR cannot be performed then patient will not be able to enter the study)
• Patient must have a Central Venous Catheter for treatment

You may not qualify if…

• Previous treatment with trabectedin or previous treatment with radiotherapy (except if previous radiotherapy treatment plus planned study radiotherapy treatment allow tissues constrains)
• Performance status ≥ 2 (ECOG).
• Plasma bilirubin > UNL.
• Creatinine > 1.6 mg/dL.
• 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.
• Severe COPD or other severe pulmonary diseases.
• Significant cardiovascular disease (for example, dyspnea > 2 NYHA)
• 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.
• Uncontrolled bacterial, mycotic or viral infections.
• Known positive test for infection by human immunodeficiency virus (HIV).
• Women who are pregnant or breast-feeding.
• Psychological, familial, social or geographic circumstances that limit the patient"s ability to comply with the protocol or informed consent.
• Patients participating in another clinical trial or receiving any other investigational product
• Patients who had participated in another clinical trial and/or had received any other investigational product in the last 30 days prior to inclusion.
• Histologies other than those described in inclusion criteria.
• Cohort B: ML
• Inclusion criteria:
• The patient must sign voluntarily the informed consent form before any study test is conducted that is not part of routine patient care.
• Age ≥18 years old.
• Pathological diagnosis of Myxoid Liposarcoma, deep located and more than 5 cm or superficial more than 10 cm. A centralized diagnostic will be performed to confirm that the patient can be included in the study.
• 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.
• Disease distribution allows meeting with normal tissue constraints of radiation therapy. Radiation oncologist must confirm this point.
• Measurable disease, according to RECIST V 1.1 criteria
• Performance status 0-1 (ECOG).
• Adequate bone marrow function (hemoglobin > 10 g/dL, leukocytes ≥ 3.000/mm3, neutrophils ≥ 1.500/mm3, platelets ≥ 100.000/mm3). Patients with plasma creatinine ≤ 1,6 mg/dL, transaminases ≤ 2.5 times the UNL, total bilirubin ≤ UNL, CPK ≤ 2.5 times UNL, alkaline phosphatase ≤ 2.5 times the UNL are acceptable. If the increase of alkaline phosphatase is > 2.5 times the UNL, then the alkaline phosphatase liver fraction and/or GGT must be ≤ UNL.

Where it is running

• Hospital Virgen del Rocío — Seville, Spain (enrolling)
• Centre Léon Berard — Lyon, France (enrolling)
• Hospital Uniersitario La Paz — Madrid, Spain (enrolling)
• Jiménez Díaz Foundation University Hospital — Madrid, Spain (enrolling)
• Institut Bergonié — Bordeaux, France (enrolling)
• Candiolo Cancer Institute — Candiolo, Italy (enrolling)
• Istituto Nazionale dei Tumori — Milan, Italy (enrolling)
• Hospital Miguel Servet — Zaragoza, Aragon, Spain (enrolling)
• Hospital Sant Pau — Barcelona, Catalonia, Spain (enrolling)
• Hospital Son Espases — Palma de Mallorca, Mallorca, Spain (enrolling)
• Hospital Universitario Canarias — San Cristóbal de La Laguna, Tenerife, Spain (enrolling)
• Hospital Vall d'Hebrón — Barcelona, Spain (enrolling)
• Hospital Puerta de Hierro — Madrid, Spain (enrolling)
• Hospital Universitario Gregorio Marañón — Madrid, Spain (enrolling)
• Istituto Clinico Humanitas — Rozzano, Milan, Italy
• Centro di Referimento Ocologico — Aviano, Italy
• Istituto Ortopedico Rizzoli — Bologna, Italy

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.