Trabectedin Plus Radiotherapy in Soft Tissue Sarcoma Patients

NCT02275286 | Recruiting Phase 1

• 1 other identifier: GEIS 37
• Study Type: interventional
• Target: 199
• Locations: 3 countries
• Sites: 17

Brief 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.

Conditions

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

Keywords

sarcoma

Outcome Measures

Primary Outcomes (2)

• Tumor size

  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.

  every 6 weeks for 24 months

• Relapse-free survival.

  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).

  5 years.

Secondary Outcomes (10)

• Number and grade of adverse events

  every 21 days until 30 days after last dose or during 25 months

• Number of months without progression

  24 months

• Number of months alive

  24 months

• Tumor size

  every 6 weeks during 24 months (cohort A) or every 4months during 36 months (cohort B and C)

• Questionnaire

  every 3 months during 24 months

Study Arms (1)

Trabectedin+Radiotherapy

EXPERIMENTAL

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

Drug: Trabectedin; Radiation: Radiotherapy

Interventions

Trabectedin DRUG

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.

Also known as: Yondelis

Trabectedin+Radiotherapy

Radiotherapy RADIATION

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).

Trabectedin+Radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.
• 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.

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
• Cohort B: ML
• The patient must sign voluntarily the informed consent form before any study test is conducted that is not part of routine patient care.

Sponsors & Collaborators

• Grupo Espanol de Investigacion en Sarcomas: lead
• Centre Leon Berard: collaborator
• Italian Sarcoma Group: collaborator

Study Sites (17)

Institut Bergonié

Bordeaux, 33000, France

RECRUITING

Centre Léon Berard

Lyon, France

RECRUITING

Istituto Clinico Humanitas

Rozzano, Milan, 20089, Italy

NOT YET RECRUITING

Centro di Referimento Ocologico

Aviano, 33081, Italy

NOT YET RECRUITING

Istituto Ortopedico Rizzoli

Bologna, 40136, Italy

NOT YET RECRUITING

Candiolo Cancer Institute

Candiolo, 10060, Italy

RECRUITING

Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

Hospital Miguel Servet

Zaragoza, Aragon, 50009, Spain

RECRUITING

Hospital Sant Pau

Barcelona, Catalonia, 08041, Spain

RECRUITING

Hospital Son Espases

Palma de Mallorca, Mallorca, 07010, Spain

RECRUITING

Hospital Universitario Canarias

San Cristóbal de La Laguna, Tenerife, 38320, Spain

RECRUITING

Hospital Vall d'Hebrón

Barcelona, 08035, Spain

RECRUITING

Hospital Puerta de Hierro

Madrid, 28006, Spain

RECRUITING

Hospital Universitario Gregorio Marañón

Madrid, 28007, Spain

RECRUITING

Hospital Uniersitario La Paz

Madrid, 28046, Spain

RECRUITING

Jiménez Díaz Foundation University Hospital

Madrid, Spain

RECRUITING

Hospital Virgen del Rocío

Seville, 41013, Spain

RECRUITING

Related Publications (3)

• Vatner R, James CD, Sathiaseelan V, Bondra KM, Kalapurakal JA, Houghton PJ. Radiation therapy and molecular-targeted agents in preclinical testing for immunotherapy, brain tumors, and sarcomas: Opportunities and challenges. Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28439. doi: 10.1002/pbc.28439. Epub 2020 Aug 22.

  PMID: 32827353 DERIVED

• Martin-Broto J, Hindi N, Lopez-Pousa A, Peinado-Serrano J, Alvarez R, Alvarez-Gonzalez A, Italiano A, Sargos P, Cruz-Jurado J, Isern-Verdum J, Dolado MC, Rincon-Perez I, Sanchez-Bustos P, Gutierrez A, Romagosa C, Morosi C, Grignani G, Gatti M, Luna P, Alastuey I, Redondo A, Belinchon B, Martinez-Serra J, Sunyach MP, Coindre JM, Dei Tos AP, Romero J, Gronchi A, Blay JY, Moura DS. Assessment of Safety and Efficacy of Combined Trabectedin and Low-Dose Radiotherapy for Patients With Metastatic Soft-Tissue Sarcomas: A Nonrandomized Phase 1/2 Clinical Trial. JAMA Oncol. 2020 Apr 1;6(4):535-541. doi: 10.1001/jamaoncol.2019.6584.

  PMID: 32077895 DERIVED

• Gronchi A, Hindi N, Cruz J, Blay JY, Lopez-Pousa A, Italiano A, Alvarez R, Gutierrez A, Rincon I, Sangalli C, Perez Aguiar JL, Romero J, Morosi C, Sunyach MP, Sanfilippo R, Romagosa C, Ranchere-Vince D, Dei Tos AP, Casali PG, Martin-Broto J. Trabectedin and RAdiotherapy in Soft Tissue Sarcoma (TRASTS): Results of a Phase I Study in Myxoid Liposarcoma from Spanish (GEIS), Italian (ISG), French (FSG) Sarcoma Groups. EClinicalMedicine. 2019 Mar 11;9:35-43. doi: 10.1016/j.eclinm.2019.03.007. eCollection 2019 Mar.

  PMID: 31143880 DERIVED

MeSH Terms

Conditions

Liposarcoma, Myxoid; Sarcoma; Leiomyosarcoma; Liposarcoma

Interventions

Trabectedin; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Muscle Tissue

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics

Study Officials

• Javier Martín-Broto, MD

  Jiménez Díaz Foundation University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adriana Rojo

CONTACT

0034912866807; adriana.crc@grupogeis.org

Elisa Cerezo, MSc

CONTACT

0034912866807; elisa.crc@grupogeis.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2014
• First Posted: October 27, 2014
• Study Start: November 1, 2014
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: May 31, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2); IT (5); ES (10)