Trabectedin Plus Radiotherapy in Soft Tissue Sarcoma Patients (TRASTS)

  • STATUS
    Recruiting
  • End date
    Jun 17, 2028
  • participants needed
    165
  • sponsor
    Grupo Espanol de Investigacion en Sarcomas
Updated on 17 June 2022
measurable disease
metastasis
cancer chemotherapy
angiosarcoma
trabectedin
fibrosarcoma
soft tissue sarcoma
liposarcoma
synovial sarcoma
undifferentiated pleomorphic sarcoma
myxofibrosarcoma
malignant fibrous histiocytoma
leiomyosarcoma
myxoid liposarcoma
mpnst
malignant peripheral nerve sheath tumor

Summary

Phase I-II trial that combines trabectedin plus radiotherapy for tumor reduction response measure in two 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) 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) A translational substudy is developed to analyse different biomarkers predictive value.

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.

Three cohorts are indicated for this trial, A: Patients with diagnosis of non-operable or unresectable or not oncologically recommended metastasectomy of limited to lung metastases soft tissue sarcoma and cohort B: Patients with locally advanced resectable Myxoid Liposarcoma, C:Patients with retroperitoneal and resectable soft tissue sarcoma (liposarcoma and leiomyosarcoma).

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 every patient.

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

Details
Condition Liposarcoma, Myxoid, Sarcoma, Soft Tissue, Leiomyosarcoma, Liposarcoma, Pleomorphic Liposarcoma
Treatment Radiotherapy, trabectedin
Clinical Study IdentifierNCT02275286
SponsorGrupo Espanol de Investigacion en Sarcomas
Last Modified on17 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

The patient must voluntarily sign the informed consent form before performing any study-specific test that is not part of the patient's usual care
Aged between 18 and 75 years
The following histological subtypes may be included: High grade leiomyosarcoma (G2-3), liposarcoma, if at least 30% of the tumour is dedifferentiated, pleomorphic liposarcoma. A centralised diagnosis will be made to confirm that the patient can be included in the study
The tumour must be located in the retroperitoneum and it must be resectable and without evidence of regional or distal spread after the appropriate staging process
The location and size of the disease in the retroperitoneum must allow for compliance with radiotherapy limitations in healthy tissue. This point must be confirmed by the site's radiation oncologist
Measurable disease according to RECIST V 1.1 criteria
ECOG performance status 0-1
Adequate haematological parameters (haemoglobin >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 ULN, total bilirubin ≤ ULN, CPK ≤2.5 times ULN, alkaline phosphatase ≤2.5 times ULN are acceptable. If the increase in alkaline phosphatase is >2.5 times the ULN, the liver fraction of alkaline phosphatase and/or GGT should be ≤ULN
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. Women of childbearing potential who participate in the study must undergo a pregnancy test before starting the study
Normal cardiac function with LVEF ≥50% by echocardiogram or MUGA
HBV and HCV serology must be performed before including the patient in the study. If HbsAg is positive, it is advisable to rule out a replicative phase (HbsAg, DNA HBV+). If positive, the patient's inclusion in the trial is not recommended, and it is at the discretion of the investigator to administer preventive treatment with lamivudine. If a potential patient is positive to anti-HCV antibodies, the presence of the virus will be ruled out with a qualitative PCR, or the patient cannot be included in the study (if the qualitative PCR test cannot be performed on the patient, they cannot be included in the study)
Patient may have had one previous chemotherapy line
The patient must have a central venous catheter for the administration of the treatment

Exclusion Criteria

Unresectable tumours
Location other than the retroperitoneum
Patients who have previously received systemic treatment (chemotherapy or trabectedin)
Patients who underwent prior local treatment for retroperitoneal sarcoma: surgery or radiotherapy in the tumour bed
ECOG performance status ≥2
Presence of metastasis or lymph node involvement of the tumour
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
Significant cardiovascular disease (e.g. dyspnoea >2 NYHA)
A significant grade 3 or greater systemic disease on the NCI-CTCAE v4.03 scale, which may limit the availability of the patient or which, in the opinion of the investigator, may contribute to the toxicity caused by the study treatment
Uncontrolled viral, mycotic or bacterial infections
Known HIV-positive patients
Pregnant or breast-feeding women
Psychological, familial, social or geographical circumstances that limit the patient's ability to comply with the protocol or informed consent form
Patients who have participated in another clinical trial and/or have received another investigational product in the 30 days prior to inclusion in the trial
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