Trial in Patients With Metastatic or Locally Advanced Leiomyosarcoma

NCT04383119 | Recruiting Phase 2

• 1 other identifier: ISG-ARTICLE
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 17

Brief 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 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

Leiomyosarcoma of Ovary; Soft Tissue Sarcoma

Keywords

advanced leiomyosarcoma

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (6)

• Overall Response Rate

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

• Overall Survival (OS)

  3 years and 5 years

• Progression free Survival (PFS)

  6 months

• Duration of response

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

• Adverse events related to the treatment

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

Other Outcomes (1)

• Exploratory objectives

  week 6, and at up to week 53

Study Arms (3)

Arm A

EXPERIMENTAL

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

Drug: Trabectedin

Arm B

ACTIVE COMPARATOR

Gemcitabine 800-1000 mg/m2 will be administered via a central venous catheter on days 1,8 every 21 days

Drug: Gemcitabine

Observational Cohort

ACTIVE COMPARATOR

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

Drug: No Intervention: Observational Cohort

Interventions

Trabectedin DRUG

Trabectedin in monotherapy

Also known as: Trabectedin arm

Arm A

Gemcitabine DRUG

Gemcitabine, control arm

Also known as: Gemcitabine arm

Arm B

No Intervention: Observational Cohort DRUG

Treatment according clinical practice

Observational Cohort

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Italian Sarcoma Group: lead
• PharmaMar: collaborator

Study Sites (17)

Azienda Ospedaliera S. Orsola-Malpighi

Bologna, BO, 40138, Italy

RECRUITING

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

Meldola, FC, Italy

RECRUITING

Nuovo Ospedale di Prato

Prato, Firenze, 59100, Italy

RECRUITING

Istituto Clinico Humanitas

Rozzano, MI, 20089, Italy

RECRUITING

Centro di Riferimento Oncologico di Aviano

Aviano, PD, 33081, Italy

NOT YET RECRUITING

Policlinico Universitario Campus Biomedico

Roma, RM, 00128, Italy

RECRUITING

IRCCS Fondazione Piemonte per l'Oncologia

Candiolo, Torino, 10060, Italy

RECRUITING

A.O.U.San Luigi Gonzaga

Orbassano, Torino, 10043, Italy

RECRUITING

Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors

Bologna, 40136, Italy

RECRUITING

H.San Martino di Genova

Genova, Italy

RECRUITING

Fondazione IRCCS INT Milano

Milan, 20133, Italy

NOT YET RECRUITING

Istituto Europeo di Oncologia

Milan, Italy

RECRUITING

IRCCS Istituto nazionale Tumori "Fondazione G.Pascale"

Naples, Italy

RECRUITING

Irccs Istituto Oncologico Veneto (Iov)

Padua, Italy

RECRUITING

Ospedale Giaccone

Palermo, Italy

RECRUITING

Istituto Regina Elena - IFO

Rome, 00100, Italy

RECRUITING

ASL Città di Torino (Dipartimento di Oncologia)

Torino, 10153, Italy

RECRUITING

Related Publications (6)

• 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.

  PMID: 25713428 BACKGROUND

• 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.

  PMID: 25795402 BACKGROUND

• 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.

  PMID: 19652065 BACKGROUND

• 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.

  PMID: 11481354 BACKGROUND

• 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.

  PMID: 22907974 BACKGROUND

• 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.

  PMID: 28882536 BACKGROUND

MeSH Terms

Conditions

Sarcoma

Interventions

Trabectedin; Gemcitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines

Study Officials

• Bruno Vincenzi, Prof/MD

  Campus Biomedico of Rome

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bruno Vincenzi, Prof/MD

CONTACT

003906-22541; b.vincenzi@unicampus.it

Emanuela Marchesi, PhD

CONTACT

003905101459; emanuela.marchesi@italiansarconmagroup.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Not applicable (open label study)
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: May 4, 2020
• First Posted: May 12, 2020
• Study Start: October 29, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (17)