ISG-ARTICLE - A Randomized Phase II Trial Comparing the Activity of trabectedIn vs Gemcitabine in Patients With Metastatic or Locally Advanced Leiomyosarcoma Pretreated With Conventional Chemotherapy

Studio Clinico

Patologia: Sarcomi dei tessuti molli e gist

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: II

Linee di trattamento: Seconda linea

Criteri di inclusione: 

- 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.

Criteri di esclusione: 

- 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
- 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.

Schema di trattamento: 

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

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

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.

Trattamento sperimentale: 

Trabectedin

Trattamento di controllo: 

Gemcitabine

Obiettivi primari dello studio: 

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

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2020-000741-13

Data di aggiornamento: 05.09.2023

Promotore

Italian Sarcoma Group I.S.G. ETS (https://www.italiansarcomagroup.org/famiglie-studi-clinici/)

Principal Investigator ITALIA

Policlinico Universitario Campus Biomedico, Roma

Riferimento: Dr. Info non disponibile

Telefono: 00000

Email: nd@nd.it

Localita: Roma