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Leiomyosarcoma of OvaryPhase 2ISG-ARTICLENCT04383119

Trial in Patients With Metastatic or Locally Advanced Leiomyosarcoma

A Phase 2 study testing Trabectedin and Gemcitabine in people with Leiomyosarcoma of Ovary and Soft Tissue Sarcoma, run by Italian Sarcoma Group at 17 sites in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Study is aimed at evaluating the activity of Trabectedin (arm A) in advanced leiomyosarcomas, having Gemcitabine (arm B) as the comparator. 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leiomyosarcoma of Ovary, Soft Tissue Sarcoma
What is being tested?
Trabectedin and Gemcitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
17 sitesItaly
Study dates
29 Oct 2021to 31 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with histologically documented diagnosis of leiomyosarcoma
  • Patients with diagnosis of unresectable or metastatic leiomyosarcoma
  • Patients who received at least on previous systemic treatment with anthracycline-based chemotherapy.
  • Patients suitable to receive gemcitabine or trabectedin therapy.
  • Measurable or evaluable disease with RECIST 1.1 criteria.
  • Evidence of progression according RECIST 1.1 during the 6 months before study entry.
Show all 15Show fewer
  • Age ≥18 years
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
  • All previous anticancer treatments must have completed ≥ 3 weeks prior to first dose of study drug.
  • 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
  • Adequate bone marrow, liver and renal function
  • Left Ventricular Ejection Fraction ≥ 50% and/or above lower institutional limit of normality.
  • Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation each cycle of chemotherapy.
  • 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 prior to any study specific procedure. The subject may also provide an optional consent for the biological/translational sub-study associated.

Who cannot join

  • Prior treatment with Trabectedin and/or Gemcitabine
  • Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation of the study drugs
  • 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.
  • Persistent toxicities with the exception of alopecia, caused by previous anticancer therapies
  • Metastatic brain or meningeal tumors
  • Active viral hepatitis
Show all 18Show fewer
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus
  • Patients with any severe and/or uncontrolled medical conditions
  • 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
  • Active clinically serious infections
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus
  • Previous treatment with radiation therapy within 14 days of first day of study drug dosing,
  • Major surgery within 4 weeks prior to study entry
  • Concomitant use of known strong CYP3A inhibitors or moderate CYP3A inhibitors
  • Concomitant use of known strong or moderate CYP3A inducers
  • Patients undergoing renal dialysis or with Creatinin Clearance <30 ml/min or Creatinine >1,5 mg/dL
  • Pregnant or breast feeding patients
  • 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

Trial locations and contacts

17 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Bruno Vincenzi, Prof/MD contact

003906-22541 ext. 1123

b.vincenzi@unicampus.it

Emanuela Marchesi, PhD contact

003905101459 ext. 78

emanuela.marchesi@italiansarconmagroup.org

17 sites in 1 country

Italy17 sites, 17 recruiting

  • Centro di Riferimento Oncologico di Aviano

    Aviano, PD, 33081

    Angela Buonadonna, MD, +39 0434 659190, abuonadonna@cro.it

    Angela Buonadonna, MD

    Not yet recruiting

  • Azienda Ospedaliera S. Orsola-Malpighi

    Bologna, BO, 40138

    Margherita Nannini, MD, +39 051 2144043, margherita.nannini@aosp.bo.it

    Margherita Nannini, MD

    Recruiting

  • Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors

    Bologna, 40136

    Toni Ibrahim, MD, +390516366 ext. 199, toni.ibrahim@ior.it

    Toni Ibrahim, MD

    Recruiting

  • IRCCS Fondazione Piemonte per l'Oncologia

    Candiolo, Torino, 10060

    Sandra Aliberti, MD, +39.011.9933 ext. 278, sandra.aliberti@ircc.it

    Sandra Aliberti, MD

    Recruiting

  • H.San Martino di Genova

    Genova

    Comandini Danila, MD, danila.comandini@hsanmartino.it

    Recruiting

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST

    Meldola, FC

    Valentina Fausti, MD, valentina.fausti@irst.emr.it

    Valentina Fausti, MD

    Recruiting

  • Fondazione IRCCS INT Milano

    Milan, 20133

    Roberta Sanfilippo, MD, +390223903 ext. 468, roberta.sanfilippo@istitutotumori.mi.it

    Roberta Sanfilippo, MD

    Not yet recruiting

  • Istituto Europeo di Oncologia

    Milan

    Elisabetta Setola, MD, elisabetta.setola@ieo.it

    Recruiting

  • IRCCS Istituto nazionale Tumori "Fondazione G.Pascale"

    Naples

    Salvatore Tafuto, Prof, s.tafuto@istitutotumori.na.it

    Recruiting

  • A.O.U.San Luigi Gonzaga

    Orbassano, Torino, 10043

    Lorenzo D'Ambrosio, MD, lorenzo.dambrosio@unito.it

    Recruiting

  • Irccs Istituto Oncologico Veneto (Iov)

    Padova

    Antonella Brunello, MD, 0039049 8215 ext. 910, antonella.brunello@ioveneto.it

    Antonella Brunello, MD

    Recruiting

  • Ospedale Giaccone

    Palermo

    Giuseppe Giuseppe, MD, giuseppe.badalamenti@unipa.it

    Giuseppe Giuseppe, MD

    Recruiting

  • Nuovo Ospedale di Prato

    Prato, Firenze, 59100

    Giacomo G. Baldi, MD, 0039057443 ext. 4766, giacomogiulio.baldi@uslcentro.toscana.it

    Giacomo G. Baldi, MD

    Recruiting

  • Policlinico Universitario Campus Biomedico

    Roma, RM, 00128

    Bruno Vincenzi, MD, +3902225411123, b.vincenzi@unicampus.it

    Bruno Vincenzi, MD

    Recruiting

  • Istituto Regina Elena - IFO

    Rome, 00100

    Virginia Ferraresi, MD, +39065266919, ferraresi@ifo.it

    Recruiting

  • Istituto Clinico Humanitas

    Rozzano, MI, 20089

    Alexia Bertuzzi, MD, +390282244540, alexia.bertuzzi@cancercenter.humanitas.it

    Alexia Bertuzzi, MD

    Recruiting

  • ASL Città di Torino (Dipartimento di Oncologia)

    Torino, 10153

    Antonella Boglione, MD, antonella.boglione@aslcittaditorino.it

    Boglione, MD

    Recruiting

Other trials in Italy

About this study

Official title: A Randomized Phase II Trial Comparing the Activity of trabectedIn vs Gemcitabine in Patients With Metastatic or Locally Advanced Leiomyosarcoma Pretreated With Conventional Chemotherapy

Study is aimed at evaluating the activity of Trabectedin (arm A) in advanced leiomyosarcomas, having Gemcitabine (arm B) as the comparator.

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.

Read the detailed description

The management of patients with leiomyosarcomas determines many difficulties. Despite patients with metastatic disease at diagnosis or who recur after initial treatment have a dismal prognosis and, except for a subset of selected patients with completely resectable disease, the median survival is less than two years.

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.

Being tested
Trabectedin, Gemcitabine, No Intervention: Observational Cohort
Keywords
advanced leiomyosarcoma
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TrabectedinDrug

    Also called Trabectedin arm

    Trabectedin in monotherapy

  • GemcitabineDrug

    Also called Gemcitabine arm

    Gemcitabine, control arm

  • No Intervention: Observational CohortDrug

    Treatment according clinical practice

Study groups in NCT04383119
Study groupRoleWhat they receive
Arm AExperimentalTrabectedin 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
Receives: Drug: Trabectedin
Arm BActive comparatorGemcitabine 800-1000 mg/m2 will be administered via a central venous catheter on days 1,8 every 21 days
Receives: Drug: Gemcitabine
Observational CohortActive comparatorTreatmen 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
Receives: Drug: No Intervention: Observational Cohort

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Compare the Growth Modulation Index (GMI) in patients treated with Trabectedin or Gemcitabine in second line

    Ratio of Time To Progression with the nth line (TTPn) of therapy to the TTPn-1 with the n-1th line.

    Measured: Week 6, week 12, week 18, week 27, week 36 and week 45

Secondary outcomes (6)

  1. Overall Response Rate

    Overall response rate according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    Measured: Week 6, week 12, week 18, week 27, week 36 and week 45

  2. Overall Survival (OS)

    Survival from the first dose treatment to death for any cause

    Measured: 3 years and 5 years

  3. Progression free Survival (PFS)

    Survival without disease progression

    Measured: 6 months

  4. Duration of response

    Duration of tumor control according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    Measured: Week 6, week 12, week 18, week 27, week 36 and week 45

  5. Adverse events related to the treatment

    Safety in term of adverse event is evaluate from the first treatment dose throughout the study according to CTCAE 5.0

    Measured: Week 3, week 6, week 9, week 12, week 18, week 27, week 36, week 45

  6. Compare the Growth Modulation Index (GMI) in patients treated with Trabectedin or Gemcitabine after second line

    Ratio of Time To Progression with the Mth line (TTPn) of therapy to the TTPn-1 with the n-1th line.

    Measured: Week 6, week 12, week 18, week 27, week 36 and week 45

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2020
  2. Study start29 Oct 2021
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
multicenter, randomized, open-label, two arms with crossover. Patients will be randomized to receive Trabectedin (arm A) or Gemcitabine (arm B). In case of progressive disease (PD) or unacceptable toxicity during the assigned treatment, the patient will switched to the other arm
Masking
None (open label)
Enrolment
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04383119
Sponsor's protocol ID
ISG-ARTICLE
Acronym
ISG-ARTICLE
Status last verified
Mar 2026
First submitted
4 May 2020
Last updated
25 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Not applicable no plan to share IPD

Publications

  • 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.

    PubMed 25713428

  • 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.

    PubMed 25795402

  • 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.

    PubMed 19652065

  • 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.

    PubMed 11481354

  • 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.

    PubMed 22907974

  • 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.

    PubMed 28882536

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trabectedin and Gemcitabine in people with Leiomyosarcoma of Ovary and Soft Tissue Sarcoma, run by Italian Sarcoma Group at 17 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 25 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Bruno Vincenzi, Prof/MD (003906-22541 ext. 1123, b.vincenzi@unicampus.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Compare the Growth Modulation Index (GMI) in patients treated with Trabectedin or Gemcitabine in second line (time frame: Week 6, week 12, week 18, week 27, week 36 and week 45). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04383119, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2026.

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