Study on Trabectedin in Advanced Rearranged Mesenchymal Chondrosarcoma

Официальное название

Phase II Study on Trabectedin in Advanced Rearranged Mesenchymal Chondrosarcoma

Обзор

Prospective, uncontrolled, investigator-initiated, phase II clinical study to explore the activity of trabectedin in a population of patients aged ≥16 years with progressive, advanced (locally advanced or metastatic)

Подробное описание

Prospective, uncontrolled, multicenter, Italian, investigator-initiated, phase II clinical study to explore the activity of trabectedin in a population of patients aged ≥16 years with progressive, advanced (locally advanced or metastatic), HEY1-NCOA2 positive MCS) , pre-treated with anthracycline-based chemotherapy.

Вмешательства

• Препарат Trabectedin
  Treatment with trabectedin: 1.5 mg/m² - 1.3 mg/m² (at investigator's discretion, with a top-dose of 2.6 total mg per cycle), given in 24-hour continuous infusion

Первичные конечные точки

• Overall tumour Response Rate, according to RECIST v 1. [Срок оценки: At weeks 6]

Вторичные конечные точки (6)

• Choi criteria response rate [Срок оценки: At weeks 6, 12,18, 30, 42]
• Overall Survival [Срок оценки: At 3 and 5 years]
• Progression Free Survival (PFS) [Срок оценки: At 3 and 5 years]
• Clinical Benefit Rate [Срок оценки: Month 6]
• Duration of response [Срок оценки: At weeks 6, 12,18, 30, 42]
• Adverse events related to the treatment [Срок оценки: Week 3, week 6, week 9, week 12, week 18, week 24, week 36, week 48, week 60, week 72]

Критерии участия

Критерии включения

• Age ≥ 16 years old
• Histological centrally confirmed diagnosis of skeletal or extra-skeletal MCS with the documented presence of HEY1-NCOA2 fusion
• Locally advanced disease and/or metastatic disease
• Measurable or evaluable disease with RECIST v1.1
• Evidence of progression by RECIST v1.1 during the 6 months before study entry
• Patients must be pre-treated with at least one prior chemotherapy treatment containing anthracyclines for the advanced phase of disease and with a maximum of 3 lines
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
• Adequate bone marrow function
• Adequate organ function
• Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation each cycle of chemotherapy.
• Cardiac ejection fraction ≥50% as measured by echocardiogram
• No history of arterial and/or venous thromboembolic event within the previous 12 months
• The patient or legal representative must be able to read and understand the informed consent form and must have been willing to give written informed consent and any locally required authorisation before any study-specific procedures, including screening evaluations, sampling, and analyses.
• Any other factors, that, at judgment of investigator, could affect the safety of the patients according to the available trabectedin safety data

Критерии исключения

• Other primary malignancy with <5 years clinically assessed disease free interval, except basal cell skin cancer, cervical carcinoma in situ or other neoplasm judged to entail a low risk of relapse
• Previous treatment with radiation therapy within 14 days of first day of study drug dosing, or patients who have not recovered from adverse events due to agents previously administered
• Previous radiotherapy to 25% of the bone marrow
• Major surgery within 2 weeks prior to study entry
• Participation in another clinical study with an investigational product, which last dose was taken less than 4 weeks prior to the start of the treatment.
• Persistent toxicities (≥ grade 2) with the exception of alopecia, caused by previous anticancer therapies.
• Pregnancy or breast feeding
• Grade III/IV cardiac problems as defined by the New York Heart Association Criteria
• Medical history of arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or pulmonary embolism within 6 months prior to the initiation of study treatment
• Known brain metastasis
• Known chronic liver disease (i.e. chronic active hepatitis and cirrhosis)
• Known diagnosis oh human deficiency virus (HIV) infection
• Active or chronic hepatitis B or C requiring treatment with antiviral therapy
• Medical history of hemorrhage or a bleeding event ≥ Grade 3 within 4 weeks prior to the initiation of study treatment
• Evidence of any other serious or unstable illness, or medical, psychological, or social condition, that could jeopardize the safety of the subject and/or his/her compliance with study procedures, or may interfere with the subject's participation in the study or evaluation of the study results
• Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
• Expected non-compliance to medical regimens

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Италия · 7 центров

• Nuovo Ospedale di Prato — Prato
• Policlinico Universitario Campus Biomedico — Roma
• Fondazione del Piemonte per l'Oncologia IRCC Candiolo — Candiolo
• Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors — Bologna
• Fondazione IRCSS Istituto Nazionale dei Tumori — Milan
• Ospedale Giaccone — Palermo
• Istituti Fisioterapici Ospitalieri - Ospedale Regina Elena — Roma

Публикации

• Lee AF, Hayes MM, Lebrun D, Espinosa I, Nielsen GP, Rosenberg AE, Lee CH. FLI-1 distinguishes Ewing sarcoma from small cell osteosarcoma and mesenchymal chondrosarcoma. Appl Immunohistochem Mol Morphol. 2011 May;19(3):233-8. doi: 10.1097/PAI.0b013e3181fd6697. PMID 21084965
• Wang L, Motoi T, Khanin R, Olshen A, Mertens F, Bridge J, Dal Cin P, Antonescu CR, Singer S, Hameed M, Bovee JV, Hogendoorn PC, Socci N, Ladanyi M. Identification of a novel, recurrent HEY1-NCOA2 fusion in mesenchymal chondrosarcoma based on a genome-wide screen of exon-level expression data. Genes Chromosomes Cancer. 2012 Feb;51(2):127-39. doi: 10.1002/gcc.20937. Epub 2011 Oct 27. PMID 22034177
• Morioka H, Takahashi S, Araki N, Sugiura H, Ueda T, Takahashi M, Yonemoto T, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Susa M, Nakayama R, Nishimoto K, Kikuta K, Horiuchi K, Kawai A. Results of sub-analysis of a phase 2 study on trabectedin treatment for extraskeletal myxoid chondrosarcoma and mesenchymal chondrosarcoma. BMC Cancer. 2016 Jul 14;16:479. doi: 10.1186/s12885-016-2511-y. PMID 27418251
• Forni C, Minuzzo M, Virdis E, Tamborini E, Simone M, Tavecchio M, Erba E, Grosso F, Gronchi A, Aman P, Casali P, D'Incalci M, Pilotti S, Mantovani R. Trabectedin (ET-743) promotes differentiation in myxoid liposarcoma tumors. Mol Cancer Ther. 2009 Feb;8(2):449-57. doi: 10.1158/1535-7163.MCT-08-0848. Epub 2009 Feb 3. PMID 19190116
• Huvos AG, Rosen G, Dabska M, Marcove RC. Mesenchymal chondrosarcoma. A clinicopathologic analysis of 35 patients with emphasis on treatment. Cancer. 1983 Apr 1;51(7):1230-7. doi: 10.1002/1097-0142(19830401)51:73.0.co;2-q. PMID 6825046

Идентификаторы

NCT: NCT04305548 · ISG-MCS

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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