Trial in Patients With Metastatic or Locally Advanced Leiomyosarcoma
NCT ID: NCT04383119
Last Updated: 2024-12-20
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
100 participants
INTERVENTIONAL
2021-10-29
2025-12-31
Brief Summary
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In addition to the randomized cohort, the study has also an observational prospective cohort which include patients who will refuse the randomization or for whom the investigator will not judge the randomization as an appropriate option.
In order to allow the participation of sites only to the prospective-observational (non randomized) cohort, it was introduced the possibility to participate to the study and receive the ethical approval only to the Observational Prospective Cohort In parallel an optional translational study will be performed, in both cohorts, to identify factors predictive of the activity of Trabectedin or Gemcitabine in this specific histotype.
Detailed Description
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At the advanced-disease stage, the main aim of treatment is to improve patient's quality of life, possibly survival, with the best compromise between toxicity and symptoms. Trabectedin (T) is a marine-derived cytotoxic approved by European MEdicine Agency (EMEA) and FDA.
It is indicated for the treatment of patients with advanced soft tissue sarcoma, after failure of anthracyclines-based chemotherapy or who are unsuitable to receive these agents.
Among Soft Tissue Sarcoma (STS), activity has been mainly detected in synovial sarcoma, liposarcoma and leiomyosarcoma. Although the response rate did not exceed 10%, T was demonstrated to provide disease control, with progression arrest rates exceeding 50% and progression-free survival rates exceeding 20% at 6 months. So far no phase II or III studies have been addressed to test the activity of T in leiomyosarcoma specifically (without differentiation between site of primary localization) in comparison with Gemcitabine.
This study is aimed at evaluating the activity of Trabectedin (arm A) in advanced leiomyosarcomas, having Gemcitabine (arm B) as the comparator. In parallel an optional translational study will be performed to identify factors predictive of the activity of Trabectedin or Gemcitabine in this specific histotype.
In addition to the randomized cohort, the study has also an observational prospective cohort which include patients who will refuse the randomization or for whom the investigator will not judge the randomization as an appropriate option.
In order to allow the participation of sites only to the prospective-observational (non randomized) cohort, it was introduced the possibility to participate to the study and receive the ethical approval only to the Observational Prospective Cohort In parallel an optional translational study will be performed, in both cohorts, to identify factors predictive of the activity of Trabectedin or Gemcitabine in this specific histotype.
Conditions
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Keywords
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Study Design
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RANDOMIZED
CROSSOVER
In case of progressive disease (PD) or unacceptable toxicity during the assigned treatment, the patient will switched to the other arm
TREATMENT
NONE
Study Groups
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Arm A
Trabectedin at the dose of 1.5 mg/m2-1.3 mg/m2 with a top-dose of 2.6 total mg per cycle (according the clinical practice in pretreated patients and in all our ISG studies) will be administered via a central venous catheter as a 24-hour infusion on day 1 of 21-days treatment cycles
Trabectedin
Trabectedin in monotherapy
Arm B
Gemcitabine 800-1000 mg/m2 will be administered via a central venous catheter on days 1,8 every 21 days
Gemcitabine
Gemcitabine, control arm
Observational Cohort
Treatmen according clinical practice (not defined in advance). The patient who will refuse randomization between Arm A and B can choose to participate to the observational cohort to the study, where they will be treated according clinical practice
No Intervention: Observational Cohort
Treatment according clinical practice
Interventions
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Trabectedin
Trabectedin in monotherapy
Gemcitabine
Gemcitabine, control arm
No Intervention: Observational Cohort
Treatment according clinical practice
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Patients with diagnosis of unresectable or metastatic leiomyosarcoma
3. Patients who received at least on previous systemic treatment with anthracycline-based chemotherapy.
4. Patients suitable to receive gemcitabine or trabectedin therapy.
5. Measurable or evaluable disease with RECIST 1.1 criteria.
6. Evidence of progression according RECIST 1.1 during the 6 months before study entry.
7. Age ≥18 years
8. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
9. All previous anticancer treatments must have completed ≥ 3 weeks prior to first dose of study drug.
10. The patient has resolution of adverse events, with the exception of alopecia, and of all clinically significant toxic effects of prior loco-regional therapy, surgery, radiotherapy or systemic anticancer therapy to ≤ Grade 1, by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
11. Adequate bone marrow, liver and renal function
12. Left Ventricular Ejection Fraction ≥ 50% and/or above lower institutional limit of normality.
13. Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation each cycle of chemotherapy.
14. No history of arterial and/or venous thromboembolic event within the previous 12 months.
15. 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 prior to any study specific procedure. The subject may also provide an optional consent for the biological/translational sub-study associated.
Exclusion Criteria
2. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
3. History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission from 5 years or more and judged of negligible potential of relapse.
4. Persistent toxicities with the exception of alopecia, caused by previous anticancer therapies
5. Metastatic brain or meningeal tumors
6. Active viral hepatitis
7. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus
8. Patients with any severe and/or uncontrolled medical conditions
9. Medical history of hemorrhage or a bleeding event ≥ Grade 3 (NCI-CTCAE v 5.0) within 4 weeks prior to the initiation of study treatment
10. Active clinically serious infections
11. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus
12. Previous treatment with radiation therapy within 14 days of first day of study drug dosing,
13. Major surgery within 4 weeks prior to study entry
14. Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors
15. Concomitant use of known strong or moderate CYP3A inducers
16. Patients undergoing renal dialysis or with Creatinin Clearance \<30 ml/min or Creatinine \>1,5 mg/dL
17. Pregnant or breast feeding patients
18. Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
18 Years
ALL
No
Sponsors
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PharmaMar
INDUSTRY
Italian Sarcoma Group
NETWORK
Responsible Party
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Principal Investigators
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Bruno Vincenzi, Prof/MD
Role: PRINCIPAL_INVESTIGATOR
Campus Biomedico of Rome
Locations
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Azienda Ospedaliera S. Orsola-Malpighi
Bologna, BO, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST
Meldola, FC, Italy
Nuovo Ospedale di Prato
Prato, Firenze, Italy
Istituto Clinico Humanitas
Rozzano, MI, Italy
Centro di Riferimento Oncologico di Aviano
Aviano, PD, Italy
Policlinico Universitario Campus Biomedico
Roma, RM, Italy
IRCCS Fondazione Piemonte per l'Oncologia
Candiolo, Torino, Italy
A.O.U.San Luigi Gonzaga
Orbassano, Torino, Italy
Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors
Bologna, , Italy
H.San Martino di Genova
Genova, , Italy
Fondazione IRCCS INT Milano
Milan, , Italy
Istituto Europeo di Oncologia
Milan, , Italy
IRCCS Istituto nazionale Tumori "Fondazione G.Pascale"
Napoli, , Italy
Irccs Istituto Oncologico Veneto (Iov)
Padua, , Italy
Ospedale Giaccone
Palermo, , Italy
Istituto Regina Elena - IFO
Rome, , Italy
ASL Città di Torino (Dipartimento di Oncologia)
Torino, , Italy
Countries
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Central Contacts
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Facility Contacts
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Margherita Nannini, MD
Role: primary
Valentina Fausti, MD
Role: primary
Giacomo G. Baldi, MD
Role: primary
Alexia Bertuzzi, MD
Role: primary
Angela Buonadonna, MD
Role: primary
Bruno Vincenzi, MD
Role: primary
Sandra Aliberti, MD
Role: primary
Lorenzo D'Ambrosio, MD
Role: primary
Toni Ibrahim, MD
Role: primary
Comandini Danila, MD
Role: primary
Roberta Sanfilippo, MD
Role: primary
Elisabetta Setola, MD
Role: primary
Salvatore Tafuto, Prof
Role: primary
Antonella Brunello, MD
Role: primary
Giuseppe Giuseppe, MD
Role: primary
Virginia Ferraresi, MD
Role: primary
Antonella Boglione, MD
Role: primary
Boglione, MD
Role: backup
References
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Hensley ML, Miller A, O'Malley DM, Mannel RS, Behbakht K, Bakkum-Gamez JN, Michael H. Randomized phase III trial of gemcitabine plus docetaxel plus bevacizumab or placebo as first-line treatment for metastatic uterine leiomyosarcoma: an NRG Oncology/Gynecologic Oncology Group study. J Clin Oncol. 2015 Apr 1;33(10):1180-5. doi: 10.1200/JCO.2014.58.3781. Epub 2015 Feb 23.
Pautier P, Floquet A, Chevreau C, Penel N, Guillemet C, Delcambre C, Cupissol D, Selle F, Isambert N, Piperno-Neumann S, Thyss A, Bertucci F, Bompas E, Alexandre J, Collard O, Lavau-Denes S, Soulie P, Toulmonde M, Le Cesne A, Lacas B, Duffaud F; French Sarcoma Group. Trabectedin in combination with doxorubicin for first-line treatment of advanced uterine or soft-tissue leiomyosarcoma (LMS-02): a non-randomised, multicentre, phase 2 trial. Lancet Oncol. 2015 Apr;16(4):457-64. doi: 10.1016/S1470-2045(15)70070-7. Epub 2015 Mar 18.
Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, Lebedinsky C, Elsayed YA, Izquierdo MA, Gomez J, Park YC, Le Cesne A. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009 Sep 1;27(25):4188-96. doi: 10.1200/JCO.2008.21.0088. Epub 2009 Aug 3.
Patel SR, Gandhi V, Jenkins J, Papadopolous N, Burgess MA, Plager C, Plunkett W, Benjamin RS. Phase II clinical investigation of gemcitabine in advanced soft tissue sarcomas and window evaluation of dose rate on gemcitabine triphosphate accumulation. J Clin Oncol. 2001 Aug 1;19(15):3483-9. doi: 10.1200/JCO.2001.19.15.3483.
Pautier P, Floquet A, Penel N, Piperno-Neumann S, Isambert N, Rey A, Bompas E, Cioffi A, Delcambre C, Cupissol D, Collin F, Blay JY, Jimenez M, Duffaud F. Randomized multicenter and stratified phase II study of gemcitabine alone versus gemcitabine and docetaxel in patients with metastatic or relapsed leiomyosarcomas: a Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) French Sarcoma Group Study (TAXOGEM study). Oncologist. 2012;17(9):1213-20. doi: 10.1634/theoncologist.2011-0467. Epub 2012 Aug 20.
Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Kuver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1397-1410. doi: 10.1016/S1470-2045(17)30622-8. Epub 2017 Sep 4.
Other Identifiers
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ISG-ARTICLE
Identifier Type: -
Identifier Source: org_study_id