Clincosm LogoSign in Get a demo

ISG-ARTICLE: Trial in Patients With Metastatic or Locally Advanced Leiomyosarcoma

Sponsor
Italian Sarcoma Group (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT04383119
Collaborator
PharmaMar (Industry)
100
Enrollment
13
Locations
3
Arms
34.1
Anticipated Duration (Months)
7.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
100 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention 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 armmulticenter, 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)
Masking Description:
Not applicable (open label study)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Oct 29, 2021
Anticipated Primary Completion Date :
Sep 1, 2024
Anticipated Study Completion Date :
Sep 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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

Drug: Trabectedin
Trabectedin in monotherapy
Other Names:
  • Trabectedin arm

    		•
    Active Comparator: Arm B

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

    Drug: Gemcitabine
    Gemcitabine, control arm
    Other Names:
  • Gemcitabine arm

    		•
    Active Comparator: 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

    Drug: No Intervention: Observational Cohort
    Treatment according clinical practice

    Outcome Measures

    Primary Outcome Measures

    1. Compare the Growth Modulation Index (GMI) in patients treated with Trabectedin or Gemcitabine in second line [Week 6, week 12, week 18, week 27, week 36 and week 45]

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

    Secondary Outcome Measures

    1. Overall Response Rate [Week 6, week 12, week 18, week 27, week 36 and week 45]

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

    2. Overall Survival (OS) [3 years and 5 years]

      Survival from the first dose treatment to death for any cause

    3. Progression free Survival (PFS) [6 months]

      Survival without disease progression

    4. Duration of response [Week 6, week 12, week 18, week 27, week 36 and week 45]

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

    5. Adverse events related to the treatment [Week 3, week 6, week 9, week 12, week 18, week 27, week 36, week 45]

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

    6. Compare the Growth Modulation Index (GMI) in patients treated with Trabectedin or Gemcitabine after second line [Week 6, week 12, week 18, week 27, week 36 and week 45]

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

    Other Outcome Measures

    1. Exploratory objectives [week 6, and at up to week 53]

      Identify gene mutations that may be associated to response/resistance to the treatment and to clinical outcomes parameters.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Patients with histologically documented diagnosis of leiomyosarcoma

    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

    1. Adequate bone marrow, liver and renal function

    2. Left Ventricular Ejection Fraction ≥ 50% and/or above lower institutional limit of normality.

    3. Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation each cycle of chemotherapy.

    4. No history of arterial and/or venous thromboembolic event within the previous 12 months.

    5. 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:

    1. Prior treatment with Trabectedin and/or Gemcitabine

    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Azienda Ospedaliera S. Orsola-Malpighi Bologna BO Italy 40138
    2 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori - IRST Meldola FC Italy
    3 Nuovo Ospedale di Prato Prato Firenze Italy 59100
    4 Istituto Clinico Humanitas Rozzano MI Italy 20089
    5 Centro di Riferimento Oncologico di Aviano Aviano PD Italy 33081
    6 Policlinico Universitario Campus Biomedico Roma RM Italy 00128
    7 I.R.C.C. - Unit of Medical Oncology Candiolo Torino Italy 10060
    8 Istituto Ortopedico Rizzoli - Unit of Chemotherapy of Muscoloskeletal Tumors Bologna Italy 40136
    9 Fondazione IRCCS INT Milano Milano Italy 20133
    10 Irccs Istituto Oncologico Veneto (Iov) Padova Italy
    11 Ospedale Giaccone Palermo Italy
    12 Istituto Regina Elena - IFO Rome Italy 00100
    13 ASL Città di Torino (Dipartimento di Oncologia) Torino Italy 10153

    Sponsors and Collaborators

    • Italian Sarcoma Group
    • PharmaMar

    Investigators

    • Principal Investigator: Bruno Vincenzi, Prof/MD, Campus Biomedico of Rome

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Italian Sarcoma Group
    ClinicalTrials.gov Identifier:
    NCT04383119
    Other Study ID Numbers:
    • ISG-ARTICLE
    First Posted:
    May 12, 2020
    Last Update Posted:
    Nov 5, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Italian Sarcoma Group
    advanced leiomyosarcoma
    Additional relevant MeSH terms:
    Sarcoma
    Leiomyosarcoma
    Gemcitabine
    Trabectedin

    Study Results

    No Results Posted as of Nov 5, 2021